CAse study
lululo
PharmacotherapeuticsForAdvancedPractice-TeriMoserWoo.pdf
FOURTH EDITION
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T
ORGANIZATION
The Foundation
PREFACE
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Pharmacotherapeutics With Single Drugs
Pharmacotherapeutics With Multiple Drugs
Special Drug Treatment Considerations
FEATURES
Unit I chapters
Unit II chapters
Unit III chapters
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Unit IV chapters
SUMMARY ACKNOWLEDGMENTS
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MARYLOU V. ROBINSON, PHD, FNP-CTERI MOSER WOO, RN, PHD, CPNP-PC, FAANP
ABOUT THE AUTHORS
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Lorena C. Guerrero, PhD, MN, ARNP, FNP-BC
Anne Hedger, DNP, ACNP-CS, ANP-CS, CPNP-AC, ENP-BC, CCRN
Leila N. Jones, MSN, BA, RN
Jennifer Jordan, RPh, PharmD, BCPS
Tracy Klein, PhD, FNP, ARNP, FAANP, FRE, FAAN
Ashim Malhotra, BPharm, PhD
Theresa Mallick-Searle, MS, RN-BC, ANP-BC
Erin Anderson, MSN, CPNP
Cally Bartley, MSN, FNP-C
Jane M. Carrington, PhD, RN
Diana L. Dewell, ARNP, ANP
Gina Dobbs, MSN, CRNP
Krista Estes, DNP, FNP-C
Teral Gerlt, MS, RN, WHCNP-E
Theresa Granger, PhD, ARNP, FNP
CONTRIBUTORS
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Fujio McPherson, RN, DAOM, MSN, FNP, LAC
Benjamin J. Miller, PhD, MN, ARNP, FNP, ACNP
Anne E. Morgan, PharmD
Joan Nelson, DNP, RN
Patricia Nodine PhD, CNM
Kristen Lambert Osborn, MSN, CPNP–AC/PC
James L. Raper, DSN, CRNP, JD, FAANP, FAAN
Peter J. Rice, PharmD, PhD, BCPS
Laura Rosenthal, DNP, ACNP
Ruth Schaffler, PhD, FNP
Tracy Scott, DNP, FNP
Kathy Shaw, DNP, RN, CDE
R. Brigg Turner, PharmD, BCPS
Connie Valdez, PharmD, MSEd, BCPS
Mary Weber, PhD, PMHNP-BC, FAANP
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Joan Parker Frizzell, PhD, CRNP, ANP-BC
Tammy Gilliam, DNP, APRN-BC, FNP
Cathy R. Kessenich, DSN, ARNP, FAANP
Pamela King, PhD, APRN, FNP, PNP
Angela I. Kulesza, DNP, NP-C
Christine Nelson-Tuttle, DNS, RN, PNP-BC
David G. O’Dell, DNP, ARPN, FNP-BC
JoAnne Pearce, MS, PhDc, RN, APRN
Marianne Adam, PhD, RN, CRNP
Nancy Beckham, PhD, FNP-C
Christopher W. Blackwell, PhD, ARNP, ANP-BC, AGACNP-BC, CNE
Sharon Chalmers, PhD, CNE, APRN-BC
Patsy E. Crihfield, DNP, APRN, FNP-BC, PMHNP-BC, PMHS
Linda Dayer-Berenson, PhD, MSN, CRNP, CNE, FAANP
Carolynn A. DeSandre, PhD, CNM, FNP-BC
Abimbola Farinde, PharmD, MS
REVIEWERS
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Julie Ponto, PhD, RN, ACNS-BC, AOCNS
Susan Quisenberry, DNP, APRN, CNP, FNP-C
Sandra Restaino, DNP, NP-C, FAANP, CSC
Maria Rosen, PhD, RN, PNP-BC
Kathleen R. Sheikh, MSN, FNP-BC
Jennifer Sipe, RN, MSN, APRN-BC
Angela Thompson, PhD, PharmD
Diane Yorke, MSN, MBA, PhD, RN, CPNP
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Chapter 16 Drugs Affecting the Cardiovascular and Renal Systems 295 Marylou V. Robinson, PhD, FNP-C
Chapter 17 Drugs Affecting the Respiratory System 361 Teri Moser Woo, PhD, CPNP
Chapter 18 Drugs Affecting the Hematopoietic System 415 Teri Moser Woo, PhD, CPNP and Kristen Lambert Osborne MSN, CPNP AC/PC
Chapter 19 Drugs Affecting the Immune System 447 Teri Moser Woo, PhD, CPNP
Chapter 20 Drugs Affecting the Gastrointestinal System 497 Teri Moser Woo, PhD, CPNP
Chapter 21 Drugs Affecting the Endocrine System 541 Marylou Robinson, PhD, FNP and Kathy Shaw, DNP, RN, CDE
Chapter 22 Drugs Affecting the Reproductive System 615 Diana L. Dewel, ARNP, ANP
Chapter 23 Drugs Affecting the Integumentary System 647 Cally Bartley, MSN, FNP-C
Chapter 24 Drugs Used in Treating Infectious Diseases 691 Jennifer Jordan, RPh, PharmD, BCPS; R. Brigg Turner, PharmD, BCPS; and Teri Moser Woo, PhD, CPNP
Chapter 25 Drugs Used in Treating Inflammatory Processes 801 Teri Moser Woo, PhD, CPNP
Chapter 26 Drugs Used in Treating Eye and Ear Disorders 837 Teri Moser Woo, PhD, CPNP
UNIT III. PHARMACOTHERAPEUTICS WITH MULTIPLE DRUGS 863
Chapter 27 Anemia 865 Teri Moser Woo, PhD, CPNP and Kristen Osborn MSN, CPNP AC/PC
Chapter 28 Chronic Stable Angina and Low-Risk Unstable Angina 881 Laura D. Rosenthal, DNP, ACNP
Chapter 29 Anxiety and Depression 897 Mary Weber, PhD, PMHNP-BC, FAANP and Krista Estes, DNP, FNP-C
UNIT I. THE FOUNDATION 1 Chapter 1 The Role of the Nurse Practitioner
as Prescriber 3 Teri Moser Woo, PhD, CPNP and Marylou V. Robinson, PhD, FNP-C
Chapter 2 Review of Basic Principles of Pharmacology 11 Peter J. Rice, PharmD, PhD, BCPS
Chapter 3 Rational Drug Selection 29 Teri Moser Woo, PhD, CPNP
Chapter 4 Legal and Professional Issues in Prescribing 37 Tracy Klein, PhD, FNP
Chapter 5 Adverse Drug Reactions 51 Connie A. Valdez, PharmD, MSEd, BCPS; Anne E. Morgan, PharmD; and Peter J. Rice, PharmD, PhD, BCPS
Chapter 6 Factors That Foster Positive Outcomes 61 Marylou V. Robinson, PhD, FNP-C and Teri Moser Woo, PhD, CPNP
Chapter 7 Cultural and Ethnic Influences in Pharmacotherapeutics 75 Lorena C. Guerrero, PhD, MS, ARNP, FNP-BC and Leila M. Jones, RN, MSN
Chapter 8 An Introduction to Pharmacogenomics 103 Ashim Malhotra, BPharm, PhD
Chapter 9 Nutrition and Neutraceuticals 115 Teri Moser Woo, PhD, CPNP
Chapter 10 Herbal Therapy and Nutritional Supplements 129 Fujio McPherson, RN, DAOM, MSN, FNP, LAC
Chapter 11 Information Technology and Pharmacotherapeutics 151 Jane M. Carrington, PhD, RN
Chapter 12 Pharmacoeconomics 159 Teri Moser Woo, PhD, CPNP
Chapter 13 Over-the-Counter Medications 165 Teri Moser Woo, PhD, CPNP
UNIT II. PHARMACOTHERAPEUTICS WITH SINGLE DRUGS 171
Chapter 14 Drugs Affecting the Autonomic Nervous System 173 Tracy Scott, DNP, FNP
Chapter 15 Drugs Affecting the Central Nervous System 225 Teri Moser Woo, PhD, CPNP
CONTENTS
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Chapter 30 Asthma and Chronic Obstructive Pulmonary Disease 913 Benjamin J. Miller, PhD, MN, ARNP, FNP, ACNP
Chapter 31 Contraception 943 Teri Gerlt, MS, RN, WCHNP
Chapter 32 Dermatological Conditions 957 Teri Moser Woo, PhD, CPNP
Chapter 33 Diabetes Mellitus 991 Kathy Shaw, DNP, RN, CDE and Marylou Robinson, PhD, FNP-C
Chapter 34 Gastroesophageal Reflux and Peptic Ulcer Disease 1021 Teri Moser Woo, PhD, CPNP
Chapter 35 Headaches 1035 Theresa Mallick-Searle, MS, RN-BC, ANP-BC
Chapter 36 Heart Failure 1063 Laura Rosenthal, DNP, ACNP
Chapter 37 Human Immunodeficiency Virus Disease and Acquired Immunodeficiency Syndrome 1081 James Raper, DSN, CRNP, JD, FAANP, FAAN and Gina Dobbs, MS, CRNP
Chapter 38 Hormone Replacement Therapy and Osteoporosis 1103 Marylou V. Robinson, PhD, FNP-C
Chapter 39 Hyperlipidemia 1129 Marylou V. Robinson, PhD, FNP-C
Chapter 40 Hypertension 1155 Marylou V. Robinson, PhD, FNP-C
Chapter 41 Hyperthyroidism and Hypothyroidism 1179 Marylou V. Robinson, PhD, FNP
Chapter 42 Pneumonia 1195 Anne Hedger, DNP, ACNP-CS, ANP-CS, CPNP-AC, ENP-BC, CCRN
Chapter 43 Smoking Cessation 1205 Benjamin J. Miller, PhD, MN, ARNP, FNP, ACNP
Chapter 44 Sexually Transmitted Diseases and Vaginitis 1217 Theresa Granger, PhD, ARNP, FNP
Chapter 45 Tuberculosis 1237 Teri Moser Woo, PhD, CPNP
Chapter 46 Upper Respiratory Infections, Otitis Media, and Otitis Externa 1253 Teri Moser Woo, PhD, CPNP
Chapter 47 Urinary Tract Infections 1267 Erin Anderson, MSN, CPNP
UNIT IV. SPECIAL DRUG TREATMENT CONSIDERATIONS 1281
Chapter 48 Women as Patients 1283 Priscilla M. Nodine, PhD, CNM
Chapter 49 Men as Patients 1303 James Raper, DNS, CRNP, JD, FAANP, FAAN
Chapter 50 Pediatric Patients 1321 Teri Moser Woo, PhD, CPNP
Chapter 51 Geriatric Patients 1337 Joan M. Nelson, DNP, RN
Chapter 52 Pain Management: Acute and Chronic Pain 1351 Ruth L. Schaffler, PhD, FNP
INDEX 1373
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UNIT I
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CHAPTER 1
Teri Moser Woo • Marylou Robinson
Other APRNs
Physician Assistants
Nurses Not in Advanced Practice Roles
CANADIAN NURSE PRACTITIONER PRACTICE, 8
CURRENT ISSUES AND TRENDS IN HEALTH CARE AND THEIR EFFECT ON PRESCRIPTIVE AUTHORITY, 8 Autonomy and Prescriptive Authority
Interdisciplinary Teams
Level of Education of Team Members
Reimbursement
N ROLES OF REGISTERED NURSES IN MEDICATION MANAGEMENT
Registered Nurses
ROLES OF REGISTERED NURSES IN MEDICATION MANAGEMENT, 3 Registered Nurses
Advanced Practice Registered Nurses
ROLES AND RESPONSIBILITIES OF APRN PRESCRIBERS, 4
ADVANCED KNOWLEDGE, 4
BENEFITS OF AN APRN AS PRESCRIBER, 5
CLINICAL JUDGMENT IN PRESCRIBING, 5
COLLABORATION WITH OTHER PROVIDERS, 7 Physicians
Pharmacists
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Advanced Practice Registered Nurses
ROLES AND RESPONSIBILITIES OF APRN PRESCRIBERS
ADVANCED KNOWLEDGE
4
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BENEFITS OF AN APRN AS PRESCRIBER
CLINICAL JUDGMENT IN PRESCRIBING
5
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Is There a Clear Indication for Drug Therapy?
What Drugs Are Effective in Treating This Disorder?
What Is the Goal of Therapy With This Drug?
Under What Conditions Is It Determined That a Drug Is Not Meeting the Goal and a Different Therapy or Drug Should Be Tried?
Are There Unnecessary Duplications With Other Drugs That the Patient Is Already Taking?
Would an Over-the-Counter Drug Be Just as Useful as a Prescription Drug?
What About Cost?
Where Is the Information to Answer These Questions?
6
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COLLABORATION WITH OTHER PROVIDERS
Physicians
Pharmacists
Other APRNs
Physician Assistants
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Nurses Not in Advanced Practice Roles
CANADIAN NURSE PRACTITIONER PRACTICE
CURRENT ISSUES AND TRENDS IN HEALTH CARE AND THEIR EFFECT ON PRESCRIPTIVE AUTHORITY
Autonomy and Prescriptive Authority
Interdisciplinary Teams
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Level of Education of Team Members
Reimbursement
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REFERENCES
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CHAPTER 2
Peter J. Rice
Intracellular Receptors Regulating Gene Expression
Enzymes
Drug Action at Receptors
Disease States and Receptors
Non-receptor Mechanisms
PHARMACOKINETICS, 18 Absorption
Distribution
Metabolism
Drug Interactions
Excretion
SUMMARY, 27
PHARMACOLOGY—THE STUDY OF DRUGS
HOW NEW DRUGS ARE DEVELOPED
PHARMACOLOGYTHE STUDY OF DRUGS, 11
HOW NEW DRUGS ARE DEVELOPED, 11
DRUG RESPONSES, 12 Dose–Response Curves
Types of Drug Responses
Expressing Drug Responses
Drug Selectivity
Drug Responses in the Real World
Brand Versus Generic Drugs
RECEPTORS, 15 Ion Channel Receptors
Receptors Coupled to G Proteins
Transmembrane Receptors
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DRUG RESPONSES
Dose–Response Curves
Types of Drug Responses
12
BOX 2–1 IDEAL DRUG PROPERTIES
• Convenient route of administration, probably taken by mouth
• Established dosage • Immediate onset of action • Produces a single desired biological action • Produces no unwanted effects • Convenient duration of action • Dosage unaffected by loss of kidney or liver function
or by disease state • Improves quality of life • Prolongs patient survival
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Expressing Drug Responses
13
BOX 2–2 EXAMPLES OF GRADED RESPONSES TO DRUGS
• Blood pressure • Heart rate • Diuresis • Bronchodilation • FEV1 • Pain (scale 1–10) • Coma score
BOX 2–3 EXAMPLES OF QUANTAL RESPONSES TO DRUGS
• Convulsions • Pregnancy • Rash • Sleep • Death
Potency differences
Drug concentration (Molar)
R es
po ns
e pe
rc en
ta ge
o f m
ax im
um
100
75
50
25
0 10-9 10-8 10-7 10-6 10-5
Figure 2–1. Concentration–effect curves for three drugs that differ in potency (i.e., the dose or concentration required to produce an effect). The drug concentration on the x-axis is expressed in molar units, representing the number of molecules in each liter of solution. The graded response is expressed as a percentage of maximum effect.
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Drug Selectivity
Drug Responses in the Real World
Brand Versus Generic Drugs
14
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15
RECEPTORS Ion Channel Receptors
“Real world” drug responses
Drug concentration (µg/mL)
R es
po ns
e pe
rc en
ta ge
o f m
ax im
um 100
75
50
25
0 0.1 1 10 100 1000
Desired effect
Placebo effect
Toxicity
Ineffective
Figure 2–2. Theoretical representation of how drugs produce effects in clinical practice. Drug concentration (x-axis) increases from left to right. Some patients will respond at low dosages, either because of the placebo effect or sensitivity to the drug. As drug concentrations increase, greater numbers of patients will respond favorably but some will also respond adversely. At some dosage or concentration, the presence of toxic effects precludes the use of higher doses in patients.
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Receptors Coupled to G Proteins
16
ACh
Na+
K+
ACh
Figure 2–3. The nicotinic acetylcholine (ACh) receptor comprises five subunits that come together to form an ion channel receptor. When ACh binds to two sites on the receptor, the ion channel opens to let sodium (Na+) and potassium (K+) cross the cell membrane to initiate a response.
Drug
G protein Effector protein
Figure 2–4. G-protein–coupled receptors are proteins that cross the cell membrane 7 times, creating a pocket in which drugs can interact. Bound drugs may stimulate the receptor to release a G protein that can interact with various effector proteins to produce physiological responses.
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Transmembrane Receptors
Intracellular Receptors Regulating Gene Expression
17
Drug
-p -pp-
-p -pp-
Figure 2–5. The insulin receptor is prototypical of tyrosine kinase re- ceptors. These receptors are brought together by extracellular drug binding (insulin in the case of the insulin receptor), which activates the intracellular enzyme tyrosine kinase. Tyrosine kinase receptors activate one another by adding a phosphorus (P) to select sites on cellular proteins, which in turn activates a physiological response.
Steroid hormone
RNA
DNA
Protein
Receptor
Figure 2–6. Steroid hormones diffuse through the cell membrane to interact with steroid receptors in the cytoplasm. The hormone– receptor pair relocates to the nucleus, where it can interact with DNA to effect RNA transcription and the synthesis of proteins.
Binding
“Transition state” Products
Enzyme
Substrate
Active site
Enzyme Enzyme
Figure 2–7. Enzymes bind to substrates and speed up biochemical reactions. Enzymes can serve as receptors to the substrate, which binds at the active site, or to drugs that control enzyme activity through binding at a different site.
Enzymes
Drug Action at Receptors
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Non-receptor Mechanisms
PHARMACOKINETICS
Absorption
Disease States and Receptors
18
BOX 2–4 EFFECTS OF ROUTE OF ADMINISTRATION
• Compliance • Bioavailability • Onset of action • Duration of action
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Site of Administration
Bioavailability
Peak Blood Levels
Parenteral Administration
Oral Administration
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Distribution
Properties That Affect Distribution
20
Time (hours)
B lo
od le
ve l (
ar bi
tra ry
) 100
80
60
40
20
0 0 63 129 15 18 21 24
20 min 60 min 120 min
Figure 2–8. Blood levels for the same dose absorbed with peak-times of 20 minutes, 60 minutes, or 120 minutes. Rapid absorption results in faster effect, but blood levels are higher with a greater likelihood of toxicity.
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21
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Metabolism
Phase I and Phase II Metabolism
22
Extracellular fluid ~1/3 of total body
P la
sm a
Extracellular fluid ~1/3 of total body
P la
sm a
Intracellular fluid ~2/3 of total body water
Extracellular fluid ~1/3 of total body
P la
sm a
Intracellular fluid ~2/3 of total body water
Intracellular fluid ~2/3 of total body water
A B
Concentration = amount/volume
C
Phenobarbital
Phase 1 Phase 2 O
O
O NH
NH
p-hydroxy-phenobarbital O
OHO
O NH
NH
p-OH-phenobarbital glucuronide
O
OOO
O
HO
OH OHHO
O NH
NH
Figure 2–10. Metabolism of phenobarbital. Phase I metabolism adds an –OH to the molecule. A water-soluble glucuronide molecule is linked to this site during phase II metabolism.
Figure 2–9. Drug concentration in the plasma following administra- tion depends on the volume of dis- tribution. If a drug is confined to plasma (A), then plasma concentra- tion will be higher compared with distribution into extracellular fluid (B) or intracellular fluid (C). Dilution in increasing volumes is shown by shading of the areas containing a drug.
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Cytochrome P450
Metabolism and Half-Life
23
BOX 2–5 DRUG-METABOLIZING ENZYMES (LISTED IN ORDER OF IMPORTANCE)
CYP3A CYP2C CYP1A CYP2E CYP2D
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Patterns of Metabolism
Drug Interactions
24
Metabolism
D ru
g ac
tiv ity
Active drug
Prodrug
Active metabolite
Inactive metabolite
Phase 1 metabolism
Phase 2 metabolism
Active metabolite
(greater solubility)
Inactive metabolite
(greater solubility)
Figure 2–11. Typical effect of metabolism (solid arrows) on drug activity. Prodrugs are metabolized to active drugs that can undergo phase I and phase II metabolism, with metabolites varying in activity, compared with the parent drug, and in solubility, which increases the likelihood of renal elimination. Sometimes metabolism produces unusual effects (dashed arrows), such as drug metabolites that retain drug activity or accumulate in the body.
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Excretion
Renal Excretion
25
Glomerulus
Proximal tube Distal tube
Loop of Henle
Reabsorption Secretion Collecting
duct
Urine Figure 2–12. Diagram of the nephron, the functional unit of the kidney. Blood vessels flowing into the glomerulus provide blood, which is filtered into the lumen, the inner opening of the nephron. As fluid passes along the nephron, transporters can either reabsorb drugs (dark arrow) back into the blood or secrete (light arrow) drugs from blood into the lumen.
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Tubular Reabsorption
Tubular Secretion
Renal Excretion of Drugs
Biliary Excretion
Other Sites of Excretion
26
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SUMMARY
REFERENCES
27
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CHAPTER 3
Teri Moser Woo
Therapeutic Factors
Safety
Cost
Patient Factors
Provider Factors
INFLUENCES ON RATIONAL PRESCRIBING, 34 Pharmaceutical Promotion
When Prescribing Recommendations Change
THE PROCESS OF RATIONAL DRUG PRESCRIBING, 29 Define the Patient’s Problem
Specify the Therapeutic Objective
Choose the Treatment
Start the Treatment
Educate the Patient
Monitor Effectiveness
DRUG FACTORS INFLUENCING DRUG SELECTION, 32 Pharmacodynamic Factors
Pharmacokinetic Factors
T
THE PROCESS OF RATIONAL DRUG PRESCRIBING
Define the Patient’s Problem
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Specify the Therapeutic Objective
Choose the Treatment
Start the Treatment
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BOX 3–1 WORLD HEALTH ORGANIZATION’S SIX-STEP MODEL OF RATIONAL PRESCRIBING
Step Description
Step 1 Define the patient’s problem. Step 2 Specify the therapeutic objective. Step 3 Choose the treatment. Step 4 Start the treatment. Step 5 Educate the patient. Step 6 Monitor effectiveness.
Source: de Vries, T. P., Henning, R. H., Hogerzeil, H. V., & Fresle, D. A. (1994). Guide to good prescribing. WHO/DAP/94.11. Geneva, Switzerland: World Health Organization.
Diagnosis Treatment
Treatment script
Analytic Slow, conscious, systematic, evidence-based, novice
Non-analytic Fast, unconscious, heuristic, experience-based, expert
Figure 3–1. Hypothetical model of therapeutic reasoning. Bissessur et al, 2009.
BOX 3–2 THE ‘I Can PresCribE A Drug’ MNEMONIC
Indication Contraindications Precautions Cost/Compliance Efficacy Adverse effects Dose/Duration/Direction
Source: Iglar, K., Kennie, N., & Bajcar, J. (2007). I Can PresCribE a Drug: Mnemonic-based teaching of rational prescribing. Family Medicine, 39(4), 236–240.
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Educate the Patient
Monitor Effectiveness
31
CLINICAL PEARL
Drugs don’t work in patients who don’t take them. —C. Everett Koop, MD
Table 3–1 Example of the Use of the ‘I Can PresCribE a Drug’ Mnemonic
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DRUG FACTORS INFLUENCING DRUG SELECTION
Pharmacodynamic Factors
Pharmacokinetic Factors
Therapeutic Factors
Safety
Cost
32
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Patient Factors
Previous Adverse Drug Reactions
Health Beliefs
Current Drug Therapy
Patient Age
Pregnancy
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Provider Factors Ease of Prescribing or Monitoring
Formularies
INFLUENCES ON RATIONAL PRESCRIBING
Pharmaceutical Promotion When Prescribing Recommendations Change
34
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REFERENCES
35
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CHAPTER 4
Tracy Klein
Systemic Solutions to Problems of Controlled Substance Prescribing
STATE LAW, 45 Jurisdiction
Writing and Transmitting the Prescription
ETHICAL ASPECTS OF PRESCRIBING, 47 Informed Consent
Prescribing for Self, Family, or Friends
Sale of Pharmaceuticals and Supplements
NURSE PRACTITIONER ROLE OUTSIDE THE UNITED STATES, 48
FEDERAL DRUG LAW, 37 History
U.S. Food and Drug Administration Regulatory Jurisdiction
The New Drug Approval Process
Official Labeling
Controlled Substance Laws
Controlled Substance Prescribing Precautions
CONTROLLED SUBSTANCE MISUSE: PRESCRIBER EDUCATION, 43 Behavioral Red Flags
Pressure to Prescribe
Enabling
When You Suspect a Patient Is Misusing Medications
FEDERAL DRUG LAW
History
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U.S. Food and Drug Administration Regulatory Jurisdiction
The New Drug Approval Process
Preclinical Research
38
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Clinical Studies
39
Adverse reaction reporting
Preclinical Investigation (Stage 1)
Range: 1–3 years
Average: 18 months
Range: 2–10 years
Average: 5 years
Range: 2 months to 10 years
Average: 24 months
Initial Synthesis
Animal Testing
Inspections
Surveys/ sampling/ testing
Clinical Investigation (Stage 2)
Clinical Phase I Trials
Short Term
Long Term
Clinical Phase III Trials
Clinical Phase II Trials
NDA Review (Stage 3)
Postmarketing studies (Stage 4)
30-day safety review NDA submitted NDA approved
Industry time FDA time Figure 4–1. New drug development timeline.
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Bioavailability Studies
Regulatory Review: New Drug Application
Accelerated Approval of a New Drug Application
Postapproval Research
Official Labeling
Off-Label Use
40
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Controlled Substance Laws Controlled Substance Prescribing Precautions
41
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42
Table 4–1 Controlled Drug Schedules
Schedule Controls Required Drug Examples
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CONTROLLED SUBSTANCE MISUSE: PRESCRIBER EDUCATION
Behavioral Red Flags
43
BOX 4–1 WEB RESOURCES FOR LEGAL AND ETHICAL ISSUES IN PRESCRIBING
National Cancer Institute Clinical Trials: http://www .cancer.gov/clinicaltrials
National Institute of Health Clinical Trials: http:// clinicaltrials.gov/ct2/home
FDA MedWatch: http://www.fda.gov/Safety/MedWatch/ default.htm
U.S. Drug Enforcement Administration: http://www .dea.gov
National Provider Identifier Number application: https://nppes.cms.hhs.gov/NPPES/Welcome.do
National Council of State Boards of Nursing: www .ncsbn.org
Institute for Safe Medication Practices: www.ismp.org Opioid Assessment, Medication Agreement and Man-
agement Tools: http://www.painedu.org/tools .asp?Tool=11
Table 4–2 Behaviors More and Less Predictive of Addiction
Probably More Predictive Probably Less Predictive
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Pressure to Prescribe
Enabling
When You Suspect a Patient Is Misusing Medications Communication Barriers
Communication Skills
Systemic Solutions to Problems of Controlled Substance Prescribing
44
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Prescription Drug Monitoring Programs
STATE LAW
Jurisdiction
45
PRESCRIBING TIPS
A few prescribing tips can help the practitioner reduce environmental facilitation of prescription misuse. First, collect and document a complete history and examina- tion before prescribing controlled substances. Do not rely on patient-supplied history, x-rays, or medical records to confirm your assessment—obtain this information di- rectly from the primary source. Passik and Weinreb (2000) advise use of the four “A’s” to guide initial and on- going assessment of medication efficacy: (1) analgesia measurement by use of pain scales or other assessment tools, (2) activities of daily living (ADLs) as measured by levels of physical and psychological functioning, (3) ad- verse effects, and (4) abuse issues.
Prescribe limited quantities without refills on a first visit, allowing additional time for patient assessment and confirmatory documentation. Educate medical and as- sistive staff in reinforcement of consistent clinic policies and procedures related to scheduling, forms, urine drug screening, records review and release, and refills. It is not uncommon for patients who do misuse substances to quickly identify the “weak link” among the treatment team and focus their energies on this person or process. Standardize expectations regarding after-hours calls, use of multiple providers, and weekend or early refills and post them where they are readily available.
Patients covered by insurance plans, including Med- icaid and Medicare, can be limited to one pharmacy or one prescriber through their payment plan. Case man- agers can often be utilized to help review and manage medication use and advocate for access to additional options for pain management and control. Other tips in- clude prescribing generic, longer-acting formulations of drugs that have less street value and writing out the quantity prescribed rather than using only numerals, which can be altered.
Medication Agreements
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Writing and Transmitting the Prescription The Prescription Format
46
Health and Wellness Clinic 5000 N. Willamette Blvd.
Portland, Oregon 503-555-1111
Anita Lee Wynne PhD, FNP-C Teri Woo, CPNP
Jane Doe DOB: 4/18/01
Amoxicillin 250 mg per 5 mL Disp: 300 mL. Give pediatric dosing spoon. Sig: 15 mL po bid X 10 days for otitis media. No refills Teri Woo, CPNP
Wt. 48 lb
Date:
Figure 4–2. Sample prescription.
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What May Be Prescribed
State-Specific Elements
Electronic Prescribing and Secure Prescribing
ETHICAL ASPECTS OF PRESCRIBING
Informed Consent
47
Figure 4–3. Sample prescription for controlled substance.
Date:
Health and Wellness Clinic 5000 N. Willamette Blvd.
Portland, Oregon 503-555-1111
Anita Lee Wynne PhD, FNP-C Teri Woo, CPNP
John Doe DOB: 6/5/51
Oxycodone 5 mg Disp: 30 (thirty) Sig: 1 tablet q4–6h pm back pain.
Do not drive or use hazardous machinery until response is known. May produce drowsiness. Do not exceed 6 tablets per day.
No refills Anita Lee Wynne, FNP-C DEA # on file in pharmacy
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Prescribing for Self, Family, or Friends
Sale of Pharmaceuticals and Supplements
NURSE PRACTITIONER ROLE OUTSIDE THE UNITED STATES
48
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REFERENCES
49
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51
CHAPTER 5
Connie A. Valdez • Anne E. Morgan • Peter J. Rice
Gender
Drug Interactions
Medical Conditions
DETECTION AND ASSESSMENT OF ADRS, 56 Responding to ADRs and Warnings
Narranjo ADR Probability Scale
ADR REPORTING, 57
SUMMARY, 59
A
MECHANISTIC CLASSIFICATION OF ADRS
MECHANISTIC CLASSIFICATION OF ADRS, 51
TIMERELATED CLASSIFICATION OF ADRS, 53
DOSERELATED ADRS, 54
SEVERITY OF ADRS, 54
COMMON CAUSES OF ADRS, 55
RISK FACTORS, 55 Genetics
Age
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52
Table 5–1 Pharmacological Adverse Drug Reactions Table 5–2 Immune-Mediated Adverse Drug Reactions
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TIME-RELATED CLASSIFICATION OF ADRS
53
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DOSE-RELATED ADRS
SEVERITY OF ADRS
54
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55
COMMON CAUSES OF ADRS
RISK FACTORS
Genetics
Age
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Gender
Drug Interactions
Medical Conditions
DETECTION AND ASSESSMENT OF ADRS
56
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Responding to ADRs and Warnings Naranjo ADR Probability Scale
ADR REPORTING
57
Table 5–3 Naranjo Adverse Drug Reaction Scoring
Naranjo Adverse Drug Reaction Scoring Yes No Not Known Score
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Figure 5–1. The FDA MedWatch form provides a mechanism for health professionals to report ADRs. Source: U.S. Food and Drug Administration, www.fda.gov/Safety/MedWatch
58
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SUMMARY
REFERENCES
59
BOX 5–1 COMMON DRUGS WITH REMS
• Isotretinoin • Extended-release and long-acting opioid analgesics • Rosiglitazone • Testosterone • Verenicline • Metoclopramide • Mifepristone • Buprenorphine and naloxone • Naltrexone
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60
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61
CHAPTER 6
Marylou V. Robinson • Teri Moser Woo
FINANCIAL IMPACTS, 67 Cost Versus Complications
Out-of-Pocket Versus Insurance
Family Versus Self
Generic Versus “New and Improved” Brand Name
Public and Private Assistance
COMMUNICATION DIFFICULTIES, 68 Non–English Speakers and Interpreters
Speech and Hearing Issues
COMMUNICATION BETWEEN PROVIDERS, 68
PATIENT’S RESPONSIBILITIES, 68
MEASURING ADHERENCE, 69 Patient Reports
Clinical Outcomes
Pill Counts
Refill Records
Biological and Chemical Markers
Medication Adherence Scales
PREDICTORS OF ADHERENCE, 70
SUMMARY, 70
OVERVIEW OF NONADHERENCE, 62 Intentional Versus Nonintentional Nonadherence
ADVERSE DRUG REACTIONS, 62
ASYMPTOMATIC CONDITIONS, 62
CHRONIC CONDITIONS, 63
KNOWLEDGE DEFICIT AND PATIENT PERCEPTION, 63 Keys to Patient Education
Health and Cultural Beliefs
Medical Terminology Literacy
Written Handouts
COGNITIVE IMPAIRMENT AND PSYCHIATRIC ILLNESS, 65 Longer-Acting Drugs
Use of Reinforcements
CAREGIVER’S ROLES, 65 The Pediatric Patient
Caregiver’s Quality of Life
Behavioral Therapy
COMPLEXITY OF DRUG REGIMEN AND POLYPHARMACY, 66 Personalized Drug Schedules
Simplifying the Regimen
T
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OVERVIEW OF NONADHERENCE Intentional Versus Nonintentional Nonadherence
ADVERSE DRUG REACTIONS
ASYMPTOMATIC CONDITIONS
62
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CHRONIC CONDITIONS
KNOWLEDGE DEFICIT AND PATIENT PERCEPTION
63
Table 6–1 Factors Contributing to Medication Adherence With Chronic Illness
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Keys to Patient Education
Health and Cultural Beliefs
Medical Terminology Literacy
Written Handouts
64
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COGNITIVE IMPAIRMENT AND PSYCHIATRIC ILLNESS
Longer-Acting Drugs
Use of Reinforcements
CAREGIVER’S ROLES
The Pediatric Patient
Caregiver’s Quality of Life
Behavioral Therapy
65
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COMPLEXITY OF DRUG REGIMEN AND POLYPHARMACY
Personalized Drug Schedules
Simplifying the Regimen
Sensory or Mobility Challenges
Cues as Reminders
66
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Scheduling Visits for Medication Follow-Up
FINANCIAL IMPACTS
Cost Versus Complications
Out-of-Pocket Versus Insurance
Family Versus Self
Generic Versus “New and Improved” Brand Name
67
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Public and Private Assistance
COMMUNICATION DIFFICULTIES
Non–English Speakers and Interpreters
Speech and Hearing Issues
COMMUNICATION BETWEEN PROVIDERS
PATIENT’S RESPONSIBILITIES
68
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MEASURING ADHERENCE
Patient Reports
Clinical Outcomes
Pill Counts
Refill Records
Biological and Chemical Markers
Medication Adherence Scales
69
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!
PREDICTORS OF ADHERENCE
SUMMARY
70
BOX 6–1 MORISKY SIMPLIFIED SELF-REPORT MEASURE OF ADHERENCE
Scoring: 0 = High Adherence; 1–2 Medium Adherence; 3–4 Low Adherence
1. Do you ever forget to take your medicine? 2. Are you careless at times about taking your
medicine? 3. When you feel better do you sometimes stop
taking your medicine? 4. Sometimes if you feel worse when you take your
medication, do you stop taking it?
Adapted from Jani, A. A., Stewart, A., Nolen, R. D., & Tavel, L. (2002). Medication adherence and patient education. Florida AIDS Education & Training Center. In HIV/AIDS primary care guide (p 87). Gainesville, FL: University of Florida Press.
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71
Patient
Five spheres of influence and multiple factors that impact adherence and self-management. M. Robinson, 2015.
Personal Influences Psychological well-being
Self-efficacy Health beliefs
Spiritual beliefs Prior success Willingness
Ability to trust
Health System Influences Access to care
Availability of specialty care Self-management support
Continuity of care providers Continuity of insurance plan coverage
Wait times Insurance coverage for medications
Pharmacy access Automatic renewals
Personalize messaging concerning adherence
Biomedical Influences Timing of diagnosis Duration of impact
Degree of physical impact Comorbidities Polypharmacy
Functional impact Anticipated trajectory of impact
Frequency of dosing Drug-to-drug interactions
Socioeconomic Influences Occupational support
Occupational demands Financial stability Educational level
Impact of costs on prior lifestyle Impact of costs on other family members
Cost of medications Transportation access
Cultural barriers and considerations Religious barriers and considerations
Rural locations Living arrangements
Housing stability Legal status
Formal dependency status
Interpersonal Influences General external social support
Familial support Familiarity with others
with similar circumstances Changes in above factors
after diagnosis Language barriers
Patient provider relationship Patient provider stability
Figure 6–1. Five spheres of influence and multiple factors that impact adherence and self-management. Robinson, M. (2015). Derived from Wheeler, K. J., Roberts, M. E., & Neiheisel, M. B. (2014). Medication adherence part two: Predictors of nonadherence and adherence. Journal of the American Association of Nurse Practitioners,26(4), 225–232.
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REFERENCES
72
Table 6–2 Factors Influencing Adherence
General Health Status Medical History, Nutritional Assessment, and Comorbidities
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73
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75
CHAPTER 7
Lorena C. Guerrero • Leila M. Jones
ASIAN AMERICANS, 87 Cultural Factors
Racial Differences in Drug Pharmacokinetics and Response
NATIVE HAWAIIAN/PACIFIC ISLANDERS, 90 Cultural Factors
Racial Differences in Drug Pharmacokinetics and Response
HISPANIC AMERICANS, 92 Cultural Factors
Racial Differences in Drug Pharmacokinetics and Response
NONHISPANIC WHITES, 95
SUMMARY, 96
U.S. DEMOGRAPHICS, 75 U.S. Demographic Groupings
Health Disparities in the United States
Cultural Influences on Care
TRANSCULTURAL NURSING CARE THEORIES, 77
STANDARDS OF CULTURAL COMPETENCY, 77
ELIMINATING HEALTH DISPARITIES, 79
ETHNOPHARMACOLOGY, 79
AFRICAN AMERICANS, 80 Cultural Factors
Racial Differences in Drug Pharmacokinetics and Response
AMERICAN INDIAN/ALASKA NATIVE GROUPS, 84 Cultural Factors
Racial Differences in Drug Pharmacokinetics and Response
T U.S. DEMOGRAPHICS
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U.S. Demographic Groupings
Health Disparities in the United States
Cultural Influences on Care
76
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TRANSCULTURAL NURSING CARE THEORIES
STANDARDS OF CULTURAL COMPETENCY
77
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78
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ELIMINATING HEALTH DISPARITIES
ETHNOPHARMACOLOGY
79
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AFRICAN AMERICANS
Cultural Factors Demographics
Education and Employment
Family Relationships
Health-Care Utilization
80
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Health Status and Other Biological Variables
81
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Health Beliefs and Practices
82
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Racial Differences in Drug Pharmacokinetics and Response
83
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AMERICAN INDIAN/ALASKA NATIVE GROUPS
Cultural Factors Demographics
Education and Employment
84
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Family Relationships
Health-Care Utilization
Health Status and Other Biological Variables
85
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Health Beliefs and Practices
86
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Racial Differences in Drug Pharmacokinetics and Response
ASIAN AMERICANS
Cultural Factors Demographics
Education and Employment
Family Relationships
87
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Health-Care Utilization
Health Status and Other Biological Variables Health Beliefs and Practices
88
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Racial Differences in Drug Pharmacokinetics and Response
89
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NATIVE HAWAIIAN AND PACIFIC ISLANDERS
Cultural Factors Demographics
Education and Employment
90
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Family Relationships
Health-Care Utilization
Health Status and Other Biological Variations
91
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Health Beliefs and Practices
Racial Differences in Drug Pharmacokinetics and Response
HISPANIC AMERICANS
Cultural Factors Demographics
Education and Employment
92
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Family Relationships
Health-Care Utilization
Health Status and Other Biological Variations
93
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Health Beliefs and Practices
94
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Racial Differences in Drug Pharmacokinetics and Response NON-HISPANIC WHITES
95
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SUMMARY
96
BOX 7–1 RESOURCES FOR CULTURALLY COMPETENT CARE
Center for Cross-Cultural Research
WESTERN WASHINGTON UNIVERSITY
Housed within an integral part of the Department of Psychology at Western Washington University, the Center for Cross- Cultural Research was started in response to the Euro-American bias in psychological theory, research, and practical applica- tions. The mission of the Center for Cross-Cultural Research is to promote culture-related research, offer courses on culture, promote exchange between cultural scientists, and disseminate the results of culture research. http://www.wwu.edu/culture/
Cross Cultural Health Care Program
The mission of the Cross Cultural Health Care Program is to serve as a bridge between communities and health-care institu- tions to ensure full access to quality health care that is culturally and linguistically appropriate. http://www.xculture.org
Diversity Rx
Diversity Rx promotes language and cultural competence to improve the quality of health care for minority, immigrant, and ethnically diverse communities. http://www.diversityrx.org
National Center for Cultural Competence
The mission of the National Center for Cultural Competence (NCCC) is to increase the capacity of health and mental health programs to design, implement, and evaluate culturally and linguistically competent service delivery systems to address growing diversity, persistent disparities, and to promote health and mental health equity. http://nccc.georgetown.edu/
PharmGKB
The PharmGKB is managed by Stanford University and is a pharmacogenomics knowledge resource that encompasses clini- cal information including dosing guidelines and drug labels, potentially clinically actionable gene-drug associations and genotype-phenotype relationships. PharmGKB collects, curates and disseminates knowledge about the impact of human ge- netic variation on drug responses.
Transcultural Nursing Society
The mission of the Transcultural Nursing Society (TCNS) is to enhance the quality of culturally congruent, competent, and equitable care that results in improved health and well-being for people worldwide. The TCNS seeks to provide nurses and other health-care professionals with the knowledge base necessary to ensure cultural competence in practice, education, research, and administration. www.tcns.org
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REFERENCES
97
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98
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99
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100
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101
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103
CHAPTER 8
Ashim Malhotra
PGLYCOPROTEIN, 111
CLINICAL IMPLICATIONS OF PHARMACOGENOMICS, 111 Adverse Drug Reactions
Warfarin
Pharmacogenetic Testing Prior to Prescribing
SUMMARY, 113
A
GENETICS REVISITED, 104
HISTORY OF PHARMACOGENETICS, 105
PHARMACOGENOMICS, 105
GENETIC DIFFERENCES OF DRUG METABOLISM, 105 Genetic Polymorphism
Phase I and Phase II Metabolism
Specific CYP450 Enzymes
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GENETICS REVISITED
104
BOX 8–1 DEFINITIONS
Genetic polymorphism: multiple differences of a DNA sequence found in at least 1% of the population
Genetics: the study of heredity and its variations Genomics: the study of the complete set of genetic in-
formation present in a cell, an organism, or species Pharmacogenetics: the study of the influence of hered-
itary factors on the response of individual organisms to drugs (Venes, 2005); the study of variations of DNA and RNA characteristics as related to drug response (U.S. Food and Drug Administration, 2010b)
Pharmacogenomics: the study of the effects of genetic differences among people and the impact that these differences have on the uptake, effectiveness, toxic- ity, and metabolism of drugs
SNP: single-nucleotide polymorphism
Source: Venes, D. (2005). Taber’s cyclopedic medical dictionary (21st ed.). Philadelphia: FA Davis; U.S. Food and Drug Adminis- tration. (2010b). Table of valid genomic biomarkers in the context of approved drug labels. Retrieved from http://www .fda.gov/RegulatoryInformation/Guidances/ucm129286.htm
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HISTORY OF PHARMACOGENETICS
PHARMACOGENOMICS
GENETIC DIFFERENCES IN DRUG METABOLISM
Genetic Polymorphism
Phase I and Phase II Metabolism
105
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106
Figure 8–2. Pharmacogenomics of acetylation in isoniazid. Plasma isoniazid concentrations in 267 patients measured 6 hours post- dose. The bimodal distribution shows the effect of an NAT-2 genetic polymorphism.
N o.
s ub
je ct
s
0
24
12
0 4 8 12
Fast rate of acetylation
Slow rate of acetylation
Plasma isoniazid (mcg/mL)
Table 8–1 Clinical Implications of Genetic Polymorphisms
Metabolizer Effect on Clinical Phenotype Drug Metabolism Implications
Specific CYP450 Enzymes CYP2D6
30
65
100
50
0 0
wt/wt
24 h
D ru
g C
on c. 100
50
0 0 50
wt/wt
wt/m
m/m 100
E ffe
ct (%
)
100
50
0 0
wt/m
24 h
D ru
g C
on c. 100
50
0 0 50
wt/wt
wt/m
m/m 100
E ffe
ct (%
)
99
100
50
0 0
m/m
24 h
D ru
g C
on c. 100
50
0 0 50
wt/wt
Drug ConcentrationTime
wt/m
m/m 100
E ffe
ct (%
)
Drug Metabolism Genotypes
Drug Receptor Genotypes
+ =
Therapeutic Effect (%)
Toxicity (%)
Genetic Polymorphism of Drug Exposure
Genetic Polymorphism
of Drug Sensitivity
Genetically Regulated Heterogeneity in Drug Effects
Efficacy Toxicity
A
75 1 35 1 10 1
B
85 <10 45 <10 10 <10
C
95 >80 50 >80 10 >80
Figure 8–1. Genetic polymorphisms and drug metabolism/receptors.
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107
Figure 8–3. Proportion of drugs metabolized by CYP450 isoenzymes.
CYP2D6 19%
CYP3A4 36%
CYP1A2 CYP2A6CYP2B6
CYP2E1
CYP2C9
CYP2C19
Table 8–2 Medications and Their Receptors
Gene Medications Drug Effect Linked to Polymorphism
Drug-Metabolizing Enzymes
Drug Targets
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CYP2C9
108
Table 8–3
Substrate Inhibitors Inducers
60
30
0 0 24 48 72
P la
sm a
no rtr
ip ty
lin e
(n m
ol /L
)
Hours
0 Functional CYP2D6 genes 1 Functional CYP2D6 genes 2 Functional CYP2D6 genes 3 Functional CYP2D6 genes 13 Functional CYP2D6 genes
Figure 8–4. European population and the CYP2D6 substrate nortriptyline.
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109
Table 8–4 ( and )
Substrate Inhibitors Inducers
35
30
25
20
15
10
5
0
2 3.7
10
20
29
Pe rc
en ta
ge o
f i nd
iv id
ua ls
Percentage Duplication of CYP2D6 Across Different Populations
Sweden Germany Spain Saudi Arabia Ethiopia
Figure 8–5. Percentage distribution of individ- uals across countries showing a duplication of an allele of CYP2D6. The figure explains the exaggerated metabolism of some drugs in the specified percentage of individuals belonging to certain ethnic backgrounds (generously as- suming ethnic homogeneity in some coun- tries) due to increased 2D6 activity.
3827_Ch08_103-114 01/07/15 12:37 PM Page 109
CYP3A4
110
Table 8–5
Substrate Inhibitors Inducers
12
10
8
6
4
2
0
Pe rc
en ta
ge o
f A lle
lic F
re qu
en cy
Percentage of Allelic Variation CYP2C9 Across Different Ethnicities
CYP2C9*2 CYP2C9 Allelic Mutations
CYP2C9*3
Caucasians Africans Asians
Figure 8–6. Percentage distribution of individuals across ethnicities exhibiting polymorphism in CYP2C9.
120
100
80
60
40
20
0
Pe rc
en ta
ge o
f A lle
lic F
re qu
en cy
Percentage of Allelic Variation VKORC1 Across Different Ethnicities
VKORC1 Allelic Variant (–1639) VKORC1
Caucasians Africans Asians
Figure 8–7. Percentage distribution of individuals across ethnicities showing variation in VKORC1.
3827_Ch08_103-114 01/07/15 12:37 PM Page 110
P-GLYCOPROTEIN
111
Parent Drug
CYP3A4
Metabolite
P-Glycoprotein
Intestinal WallSmall Intestine Enteric Blood Flow
Figure 8–8. Drug–metabolism interactions.
CLINICAL IMPLICATIONS OF PHARMACOGENOMICS
Adverse Drug Reactions
Warfarin
Pharmacogenetic Testing Prior to Prescribing
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112
Table 8–6 U.S. Food and Drug Administration Positions on Necessity of Pharmacogenetic Testing as Indicated on Drug Labeling
Pharmacogenetic Biomarker Drug
Test Required
Test Recommended
Information Only
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SUMMARY
REFERENCES
113
Table 8–7 FDA-Approved Diagnostic Test Commercially Available for Commonly Prescribed Pharmacologic Therapies
Genetic Test Drug Benefit of Genetic Test
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114
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115
Teri Moser Woo
NUTRIENTDRUG INTERACTIONS, 115 Influence of Diet on the Pharmacokinetics of Drugs
Drug-Induced Nutrient Depletion
Outcomes of Nutrient–Drug Interactions
NUTRITIONAL MANAGEMENT, 118
NUTRACEUTICALS, 119 Fiber
Vitamins and Minerals
Fatty Acids
Plant Sterols
Pre-, Pro-, and Symbiotics
E
NUTRIENT–DRUG INTERACTIONS
Influence of Diet on the Pharmacokinetics of Drugs Drug Absorption
CHAPTER 9
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Drug Metabolism
116
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Drug Excretion
Drug-Induced Nutrient Depletion
Outcomes of Nutrient–Drug Interactions Clinical Decision Making
117
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NUTRITIONAL MANAGEMENT
118
Table 9–1 Vitamin K Content in Common Foods
Food Serving Size Daily Value (%)
Foods High in Vitamin K (more than Eat No More Than 1 Serving per Day or equal to 200% DV)
Foods Moderately High in Vitamin K Eat No More Than 2 Servings per Day (60% to 199% DV)
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NUTRACEUTICALS
Fiber
119
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Vitamins and Minerals
Vitamin A
120
Table 9–2 Recommended Fiber Intake
Gender/Age Fiber (g/d)
Table 9–3 Recommended Reference Intakes of Vitamins and Minerals
Nutrient Age RDA Food Sources
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121
Table 9–3 Recommended Reference Intakes of Vitamins and Minerals—cont’d
Nutrient Age RDA Food Sources
Vitamin B1
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Vitamin B2
Vitamin B3
Vitamin B6
Vitamin B12
Vitamin C
122
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Vitamin D
Vitamin K
Folate
123
Table 9–4 Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health*
ng/mL** nmol/L** Health Status
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Calcium
Iron
Fatty Acids
124
BOX 9–1 MEDICATIONS INTERFERING WITH FOLATE UTILIZATION
Antiepileptic drugs (phenytoin, primidone) Metformin Sulfasalazine Triamterene Methotrexate Barbiturates Trimethoprim Pyrimethamine Isoniazid Oral contraceptives
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Plant Sterols
Pre-, Pro-, and Symbiotics
125
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REFERENCES
126
BOX 9–2 RESOURCES
American Dietetic Association http://www.eatright.org
Drugs.com Drug Interaction Checker http://www.drugs.com/drug_interactions.php
Food and Medication Interactions http://www.foodmedinteractions.com
Medscape Drug Interaction Checker www.medscape.com
National Institutes of Health Office of Dietary Supplements http://ods.od.nih.gov/Health_Information/Health_ Information.aspx
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127
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128
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129
CHAPTER 10
Fujio McPherson
Ayurvedic Herbs
Herbs for Common Disorders
HERBAL PREPARATIONS, 147
CONSIDERATIONS FOR THE APN PRESCRIBER, 147
SUGGESTED READING, 148 Western Herbs
Chinese Medicine
Ayurvedic Medicine
General Recommendations
P
OVERVIEW OF HERBAL MEDICINE, 130
DEFINITIONS, 130 Western Herbal Medicine
Traditional Chinese Medicine
Ayurvedic Medicine
HERBAL SAFETY, 133 Evidence Grading
Matrix for Evidence Grading
Challenges to Using an Evidence-Based Method
COMMON HERBS, 138 Western Herbs
Traditional Chinese Herbs
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OVERVIEW OF HERBAL MEDICINE
DEFINITIONS
130
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Western Herbal Medicine
Traditional Chinese Medicine
131
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Ayurvedic Medicine
132
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133
HERBAL SAFETY
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Evidence Grading
Natural Standard
Healthnotes
Rakel Evidence Versus Harm Scale
Cochrane Database of Systematic Reviews
German Commission E Monographs
134
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Matrix for Evidence Grading
135
Hypertension
CAM Therapy Natural Standard Healthnotes Rakel WHO Commission- E
Cochrane Summary:
Clinical Implications for Practice: Hypertension
Herb/Supplement Indications Contraindications Dose Rakel Harm Scale
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136
Hypertension Commentary
Hyperlipidemia
CAM Therapy Natural Standard Healthnotes Rakel WHO Commission- E
Cochrane Summary:
Clinical Implications for Practice: Hyperlipidemia
Herb/Supplement Indications Contraindications Dose Rakel Harm Scale
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Hyperlipidemia Commentary
Challenges to Using an Evidenced- Based Model
137
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COMMON HERBS
Western Herbs Mental Health Symptoms
138
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139
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140
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141
3827_Ch10_129-150 01/07/15 12:34 PM Page 141
Traditional Chinese Herbs
The Four Energies
142
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The Five Flavors
The Four Movements
Meridian Routes
Actions
Herbal Formulas
How to Take Chinese Herbs
Rules for Taking a Formula
143
3827_Ch10_129-150 01/07/15 12:34 PM Page 143
Insomnia
Heart–Spleen Deficiency
144
CLINICAL PEARL
TCM diagnosis Although this text does not cover TCM diagnosis or an explanation of the disorder mentioned (e.g., spleen de- ficiency, heart fire, etc.), the general purpose of includ- ing the differential diagnosis is to demonstrate how diverse TCM diagnosis is and how it applies to the choice of herbal medicine prescribed. Please refer to TCM textbooks to further understand TCM diagnosis.
3827_Ch10_129-150 01/07/15 12:34 PM Page 144
Ayurvedic Herbs
Additional Approach to Choosing
Digestive Disorders
Rejuvenative Disorders
145
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Herbs for Common Disorders
146
Table 10–1 Selective Herbal Agents Used for Common Conditions
Condition Treatment
Pain
3827_Ch10_129-150 01/07/15 12:34 PM Page 146
HERBAL PREPARATIONS
CONSIDERATIONS FOR THE APRN PRESCRIBER
147
BOX 10–1 WEB-BASED RESOURCES FOR HERBS AND ALTERNATIVE THERAPIES
• American Botanical Council, http://www .herbalgram.org
• American Herbalist Guild, http://www .americanherbalistsguild.com
• Biofeedback Certification Institute of America, http://www.bcia.org
• National Center for Complementary and Alternative Medicine, http://nccam.nih.gov
• Natural Standard: The Authority on Integrative Medicine, http://www.naturalstandard.com/
• Cochrane Database of Systematic Reviews, http:// www.cochran.org
3827_Ch10_129-150 01/07/15 12:34 PM Page 147
SUGGESTED READING
Western Herbs
Chinese Medicine
Ayurvedic Medicine
General Recommendations
REFERENCES
148
BOX 10–2 HERBAL RESOURCES
East West School of Herbology
P.O. Box 275 Ben Lomond, CA 95005 1-800-717-5010 [email protected] or www
.planetherbs.com Sponsor of planetary herbal formulas that supplies
Western, Eastern, and Ayurvedic herbs.
Herb Pharm
Box 116 Williams, OR 97544 1-800-348-4372 Specializing in herbal tinctures. www.herb-pharm.com
Spring Wind Herb Company
2325 4th Street #6 Berkeley, CA 94710 Good source for Chinese herbs.
Banyan Botanical
6705 Eagle Rock Ave, NE Albuquerque, NM 87113 1-800-953-6424 www.banyanbotanicals.com Good source for Ayurvedic herbs.
Mountain Rose Herbs
P.O. Box 50220 Eugene, OR 97405 1-800-879-3337 www.mountainroseherbs.com Large selection of bulk organic herbs, spices, teas, es-
sential oils, and bulk ingredients.
The Tao of Tea
3430 SE Belmont Street Portland OR 97214 1-503-736-0198 www.taooftea.com Good selection of herbal teas.
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149
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150
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151
CHAPTER 11
Jane M. Carrington
MEDICATION RECONCILIATION, 154
PATIENT PRIVACY, 155
PATIENT EDUCATION, 155
QUALITY IMPROVEMENT, 156
CONCLUSION, 157
OVERVIEW INTRODUCTION
OVERVIEW, 151
INTRODUCTION, 151
THE ELECTRONIC HEALTH RECORD, 152 Information Storage and Exchange
Computerized Provider Order Entry
CLINICAL DECISION SUPPORT SYSTEMS, 154
PATIENT SAFETY, 154
3827_Ch11_151-158 01/07/15 12:58 PM Page 151
THE ELECTRONIC HEALTH RECORD
152
Information Storage and Exchange
Table 11–1 Core Elements for Meaningful Use for Providers
Associated with Core Element Measures Pharmacotherapeutics
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Computerized Provider Order Entry
153
Table 11–2 Advantages and Disadvantages of Computerized Provider Order Entry
Resource Advantages Resource Advantages
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CLINICAL DECISION SUPPORT SYSTEMS
PATIENT SAFETY
MEDICATION RECONCILIATION
154
3827_Ch11_151-158 01/07/15 12:58 PM Page 154
PATIENT PRIVACY
PATIENT EDUCATION
155
3827_Ch11_151-158 01/07/15 12:58 PM Page 155
QUALITY IMPROVEMENT
156
Table 11–3 Suggestions for Screening Web Sites
Web Site/Source Screening Suggestions
3827_Ch11_151-158 01/07/15 12:58 PM Page 156
CONCLUSION
REFERENCES
157
BOX 11–1 SAMPLE QUESTIONS FOR QUALITY IMPROVEMENT
1. In this practice, are we consistent in ordering specific laboratory tests at specific time intervals for patients on medication XXX with a diagnosis of XXX?
2. Are patients who take medication XXX receiving education about nutrition, what to exclude from a diet?
3. For this diagnosis, are patients avoiding readmission with XXX medication?
4. In this practice, are we consistent in how we educate patients about medication XXX?
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158
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159
CHAPTER 12
Teri Moser Woo
APPLYING PHARMACOECONOMICS TO PRACTICE, 163 Prescribing Generic Versus Brand-Name Medications
Medicare Part D
CONCLUSION, 164
T
PHARMACOECONOMIC STUDIES
PHARMACOECONOMIC STUDIES, 159 Components of Well-Designed Studies
Cost-of-Illness Analysis
Cost-Minimization Analysis
Cost-Effectiveness Analysis
Cost-Benefit Analysis
Cost-Utility Analysis
IMPACT OF GENERIC DRUGS ON DRUG THERAPY, 162 Generic Substitution
Generic Bioequivalence
3827_Ch12_159-164 01/07/15 12:57 PM Page 159
Components of Well-Designed Studies
160
Table 12–1 Factors Influencing Pharmacoeconomic Outcomes
Research Type
Table 12–2 Commonly Used Pharmacoeconomic Research Methodologies
Method Outcome Examples
3827_Ch12_159-164 01/07/15 12:57 PM Page 160
Cost-of-Illness Analysis
Cost-Minimization Analysis
Cost-Effectiveness Analysis
Cost-Benefit Analysis
Cost-Utility Analysis
161
3827_Ch12_159-164 01/07/15 12:57 PM Page 161
IMPACT OF GENERIC DRUGS ON DRUG THERAPY Generic Substitution
Generic Bioequivalence
162
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163
Pharmaceutical Equivalents
Therapeutic Equivalents
Bioequivalence
APPLYING PHARMACOECONOMICS TO PRACTICE
Prescribing Generic Versus Brand-Name Medications
Medicare Part D
3827_Ch12_159-164 01/07/15 12:57 PM Page 163
CONCLUSION
REFERENCES
164
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165
CHAPTER 13
Teri Moser Woo
ABUSE OF OTC MEDICATIONS, 168
PATIENT EDUCATION REGARDING OTC MEDICATIONS, 168
SUMMARY, 169
P
OVER-THE-COUNTER MEDICATIONS
OVERTHECOUNTER MEDICATIONS, 165
OTC MEDICATION SALES, 166
SELFPRESCRIBING OF OTC MEDICATIONS, 166
HAZARDS OF OTC SELFMEDICATION, 167
ADVERSE EFFECTS OF OTC SELFMEDICATION, 167 Adverse Effects
Drug Interactions
3827_Ch13_165-170 01/07/15 12:57 PM Page 165
OTC MEDICATION SALES
166
SELF-PRESCRIBING OTC MEDICATIONS
Table 13–1 Conditions for Which OTC Drugs Are Marketed
3827_Ch13_165-170 01/07/15 12:57 PM Page 166
HAZARDS OF OTC SELF-MEDICATION
ADVERSE EFFECTS OF OTC SELF-MEDICATION
Adverse Effects
167
Table 13–2 Over-the-Counter Medications That May Impair Driving or Operating Machinery
Medication OTC Products
3827_Ch13_165-170 01/07/15 12:57 PM Page 167
Drug Interactions
Antacids
Anticholinergics
Central Nervous System Depressants
NSAIDS and Aspirin
ABUSE OF OTC MEDICATIONS
PATIENT EDUCATION REGARDING OTC MEDICATIONS
168
3827_Ch13_165-170 01/07/15 12:57 PM Page 168
SUMMARY
REFERENCES
169
BOX 13–1 PATIENT EDUCATION REGARDING OTC MEDICATIONS
• Read the label of the medication to determine dose, duration of treatment, adverse effects, and drug interactions.
• If you do not understand the label information, ask a pharmacist or your health-care provider to clarify.
• Inform your provider and the pharmacist of any OTC medications you are taking, even medications you only take occasionally.
• Do not drive or operate machinery if you take sedating OTC medications. You may be charged with driving under the influence.
• Inform your provider if you have any adverse effects from the OTC medication.
BOX 13–2 OVER-THE-COUNTER MEDICATION RESOURCES
American College of Preventive Medicine Over the Counter Medications Time Tool http://www.acpm.org/?OTCMeds_ClinRef
Consumer Healthcare Products Association www.chpa.org http://otcsafety.org/
Scholastic OTC Literacy for Teachers http://www.scholastic.com/otcliteracy/
U.S. Food and Drug Administration Educational Resources: Understanding Over-the-
Counter Medicine http://www.fda.gov/Drugs/ResourcesForYou/
Consumers/
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170
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UNIT II
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173
T
CHAPTER 14
Tracy Scott
ADRENERGIC AGONISTS, 174
ALPHA2 AGONISTS: CENTRAL, 174 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ADRENERGIC ANTAGONISTS, 181
ALPHA1 ANTAGONISTS, 181 Nonselective Alpha Antagonists
Selective Alpha1 Antagonists
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
BETAADRENERGIC ANTAGONISTS BLOCKERS, 187 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
COMBINED ALPHA AND BETAADRENERGIC ANTAGONISTS, 196 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CHOLINERGIC AGONISTS, 200
MUSCARINIC AGONISTS, 200 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CHOLINESTERASE INHIBITORS, 202 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CHOLINERGIC BLOCKERS, 213 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
3827_Ch14_171-224 01/07/15 12:55 PM Page 173
ALPHA2 AGONISTS: CENTRAL
Pharmacodynamics
174
Resting activity
+–
+–
+–
Resting activity
PNS SNS
PNS SNS
PNS SNS
Resting activity
Figure 14–1. Resting activity and the autonomic nervous system.
ADRENERGIC AGONISTS
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175
Table 14–1 Actions of Autonomic Nervous System Based on Receptor
Organ or Tissue Receptor Adrenergic Effect Receptor Cholinergic Effect
3827_Ch14_171-224 01/07/15 12:55 PM Page 175
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
176
Table 14–1 Actions of Autonomic Nervous System Based on Receptor—cont’d
Organ or Tissue Receptor Adrenergic Effect Receptor Cholinergic Effect
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177
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Table 14–2 ! Pharmacokinetics: Selected Centrally Acting Alpha2 Agonists
Protein Drug Onset Peak Duration Binding Bioavailability Half-Life Elimination
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178
Table 14–3 " Drug Interactions: Centrally Acting Alpha2 Agonists
Drug Interacting Drug Possible Effect Implications
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179
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
3827_Ch14_171-224 01/07/15 12:55 PM Page 179
180
Table 14–4 # Schedule: Centrally Acting Alpha2 Agonists
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 180
ADRENERGIC ANTAGONISTS
ALPHA1 ANTAGONISTS
Nonselective Alpha Antagonists
Selective Alpha1 Antagonists
Pharmacodynamics
181
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Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
182
Table 14–5 Selected Alpha1-Adrenergic Antagonists
Protein Drug Onset Peak Duration Binding (%) Bioavailability (%) Half-Life Elimination
3827_Ch14_171-224 01/07/15 12:55 PM Page 182
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
183
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184
Table 14–6 # Dosage Schedule: Selected Alpha1-Adrenergic Antagonists
Drug Indication Form Initial Dose Maintenance Dose
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185
Table 14–7 " Drug Interactions: Selected Alpha1-Adrenergic Antagonists
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 185
Rational Drug Selection
Monitoring
Patient Education
186
3827_Ch14_171-224 01/07/15 12:55 PM Page 186
BETA-ADRENERGIC ANTAGONISTS (BLOCKERS)
Pharmacodynamics
Cardiovascular Effects
Renal Effects
Respiratory Effects
Ocular Effects
Metabolic and Endocrine Effects
187
3827_Ch14_171-224 01/07/15 12:55 PM Page 187
Effects on Other Systems
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
188
Table 14–8 ! Pharmacokinetics: Selected Beta Blockers
Protein Drug Onset Peak Duration Binding (%) Bioavailability (%) Half-Life Elimination
3827_Ch14_171-224 01/07/15 12:55 PM Page 188
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
189
3827_Ch14_171-224 01/07/15 12:55 PM Page 189
Drug, Food, and Laboratory Test Interactions
190
CLINICAL PEARL
For patients with diabetes who must take a beta blocker, the diaphoresis associated with hypoglycemia is not masked by these drugs. Patients should be taught to recognize this indication of possible hypo- glycemia and test their blood glucose levels whenever unexplained diaphoresis occurs.
Table 14–9 " Drug Interactions: Selected Beta Blockers
Drug Interacting Drug Possible Effect Implications
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191
Table 14–9 " Drug Interactions: Selected Beta Blockers—cont’d
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 191
Clinical Use and Dosing
192
3827_Ch14_171-224 01/07/15 12:55 PM Page 192
Rational Drug Selection
Monitoring
Patient Education
193
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194
Table 14–10 # Dosage Schedule: Selected Beta Blockers
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 194
195
Table 14–10 # Dosage Schedule: Selected Beta Blockers—cont’d
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 195
COMBINED ALPHA- AND BETA-ADRENERGIC ANTAGONISTS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
196
3827_Ch14_171-224 01/07/15 12:55 PM Page 196
Adverse Drug Reactions
Drug, Food, and Laboratory Test Interactions
197
Table 14–11 ! Pharmacokinetics: Combined Alpha-Beta Blockers
Protein Drug Onset Peak Duration Binding Bioavailability Half-Life Elimination
3827_Ch14_171-224 01/07/15 12:55 PM Page 197
Clinical Use and Dosing
198
Table 14–12 " Drug Interactions: Combined Alpha-Beta Blockers
Drug Interacting Drug* Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 198
199
Table 14–13 # Dosage Schedule: Combined Alpha-Beta Blockers
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 199
Monitoring
Patient Education
CHOLINERGIC AGONISTS
MUSCARINIC AGONISTS
Pharmacodynamics
200
3827_Ch14_171-224 01/07/15 12:55 PM Page 200
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
201
3827_Ch14_171-224 01/07/15 12:55 PM Page 201
Clinical Use and Dosing
Patient Education
CHOLINESTERASE INHIBITORS
Pharmacodynamics
202
3827_Ch14_171-224 01/07/15 12:55 PM Page 202
Pharmacokinetics Absorption and Distribution
203
Table 14–14 ! Pharmacokinetics: Selected Acetylcholinesterase Inhibitors
Protein Drug Onset Peak Duration Binding (%) Bioavailability Half-Life Elimination
3827_Ch14_171-224 01/07/15 12:55 PM Page 203
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
204
3827_Ch14_171-224 01/07/15 12:55 PM Page 204
Adverse Drug Reactions
Drug Interactions
205
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206
Table 14–15 " Drug Interactions: Selected Acetylcholinesterase Inhibitors
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 206
207
Table 14–15 " Drug Interactions: Selected Acetylcholinesterase Inhibitors—cont’d
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 207
Clinical Use and Dosing
208
3827_Ch14_171-224 01/07/15 12:55 PM Page 208
Rational Drug Selection
209
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210
Table 14–16 # Dosage Schedule: Acetylcholinesterase Inhibitors
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 210
Monitoring
211
Table 14–16 # Dosage Schedule: Acetylcholinesterase Inhibitors—cont’d
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 211
Patient Education
212
Table 14–17 ! Pharmacokinetics: Selected Cholinergic Blockers
Drug Onset Peak Duration Half-Life Elimination
3827_Ch14_171-224 01/07/15 12:55 PM Page 212
CHOLINERGIC BLOCKERS
Pharmacodynamics
213
3827_Ch14_171-224 01/07/15 12:55 PM Page 213
Cardiovascular Effects
Respiratory Effects
Exocrine Gland Effects
Urinary and Gastrointestinal Effects
Central Nervous System Effects
Optic Effects
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
214
3827_Ch14_171-224 01/07/15 12:55 PM Page 214
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions Drug Interactions
215
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216
Table 14–18 " Drug Interactions: Selected Cholinergic Blockers
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 216
Clinical Use and Dosing
217
Table 14–18 " Drug Interactions: Selected Cholinergic Blockers—cont’d
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 217
218
Table 14–19 # Dosage Schedule: Selected Cholinergic Blockers
Drug Indication Form Initial Dose Maintenance and Maximum Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 218
219
Table 14–19 # Dosage Schedule: Selected Cholinergic Blockers—cont’d
Drug Indication Form Initial Dose Maintenance and Maximum Dose
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220
3827_Ch14_171-224 01/07/15 12:55 PM Page 220
Rational Drug Selection
221
3827_Ch14_171-224 01/07/15 12:55 PM Page 221
Monitoring
Patient Education
REFERENCES
222
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223
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224
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225
T
CHAPTER 15
Teri Moser Woo
ANOREXIANTS
ANTICONVULSANTS, 228 HYDANTOINS
IMINOSTILBENES
SUCCINIMIDES
DRUGS THAT AFFECT GABA
LEVETIRACETAM
LAMOTRIGINE
ANTIDEPRESSANTS, 245 TRICYCLIC ANTIDEPRESSANTS TCAs
MONOAMINE OXIDASE INHIBITORS MAOIs
SELECTIVE SEROTONIN REUPTAKE INHIBITORS SSRIs
SEROTONINNOREPINEPHRINE REUPTAKE INHIBITORS SNRIs
ANTIPSYCHOTICS APs, 255 TYPICAL ANTIPSYCHOTICS
ATYPICAL ANTIPSYCHOTICS
DOPAMINERGICS
ANXIOLYTICS ANTIANXIETY AND HYPNOTICS, 267 BENZODIAZEPINES
SEROTONERGIC ANXIOLYTICS
BARBITURATES
SEDATIVEHYPNOTICS
BENZODIAZEPINE HYPNOTICS
NONBENZODIAZEPINE HYPNOTICS
MOOD STABILIZERS, 276 LITHIUM
VALPROATES
NONCLASSIFIED MOOD STABILIZERS
MUSCLE RELAXANTS AND ANTISPASMOTICS, 281 CENTRALLY ACTING MUSCLE RELAXANTS
DIRECTACTING ANTISPASMOTICS
OPIOID ANALGESICS AND THEIR ANTAGONISTS
STIMULANTS
3827_Ch15_225-294 02/07/15 2:48 PM Page 225
ANOREXIANTS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
226
Table 15–1 ! Pharmacokinetics: Anorexiants
Drug Onset Peak Duration Half-Life Excretion
3827_Ch15_225-294 02/07/15 2:48 PM Page 226
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
ANTICONVULSANTS
227
Table 15–2 " Drug Interactions: Anorexiants
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 227
HYDANTOINS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Pharmacotherapeutics Precautions and Contraindications
228
Table 15–3 # Dosage Schedule: Anorexiants
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 228
229
Table 15–4 ! Pharmacokinetics: Antiepileptic Drugs
Drug Onset Peak Duration Half-Life Excretion
Adverse Drug Reactions
3827_Ch15_225-294 02/07/15 2:48 PM Page 229
Drug Interactions
230
Possible Effect Implications
Table 15–5 " Drug Interactions: Hydantoins (Anticonvulsants
Drug Interacting Drug
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231
Table 15–5 " Drug Interactions: Hydantoins (Anticonvulsants)—cont’d
Drug Interacting Drug Possible Effect Implications
Clinical Use and Dosing
Rational Drug Selection
Monitoring Patient Education
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232
Table 15–6 # Dosage Schedule: Selected Anticonvulsants
Drug Indications Dosage Available Dosage Forms
Drugs That Affect GABA
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233
Table 15–6 # Dosage Schedule: Selected Anticonvulsants—cont’d
Drug Indications Dosage Available Dosage Forms
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234
Table 15–6 # Dosage Schedule: Selected Anticonvulsants—cont’d
Drug Indications Dosage Available Dosage Forms
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IMINOSTILBENES
Pharmacodynamics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
235
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Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
236
Table 15–7 " Drug Interactions: Carbamazepine and Oxcarbazepine (Anticonvulsants)
Drug Interacting Drug Possible Effect Implications
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237
Table 15–8 # Dosage Schedule: Carbamazepine and Oxcarbazepine (Anticonvulsants)
Drug Indications Dosage Available Dosage Forms
Patient Education
SUCCINIMIDES
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion.
3827_Ch15_225-294 02/07/15 2:48 PM Page 237
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
DRUGS THAT AFFECT GABA
Pharmacodynamics
238
Table 15–9 # Dosage Schedule: Succinimides (Anticonvulsants)
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 238
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
239
Table 15–10 ! Pharmacokinetics: Tricyclic Antidepressants
Drug Onset Peak Duration Half-Life Excretion
3827_Ch15_225-294 02/07/15 2:48 PM Page 239
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
240
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Rational Drug Selection
Monitoring
Patient Education
LEVETIRACETAM
Pharmacodynamics
241
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Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
242
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LAMOTRIGINE
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
243
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
244
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Rational Drug Selection
Monitoring
Patient Education
ANTIDEPRESSANTS
TRICYCLIC ANTIDEPRESSANTS TCAs
245
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Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
246
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247
Table 15–11 " Drug Interactions: Tricyclic Antidepressants
Drug Interacting Drug Possible Effect Implications
Table 15–12 # Dosage Schedule: Tricyclic Antidepressants
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 247
Rational Drug Selection
Monitoring
Patient Education
MONOAMINE OXIDASE INHIBITORS MAOIs
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Onset, Peak, and Duration
Pharmacotherapeutics Precautions and Contraindications
248
Table 15–12 # Dosage Schedule: Tricyclic Antidepressants—cont’d
Drug Indications Dosage Available Dosage Forms
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Adverse Drug Reactions
Clinical Use and Dosing
Drug and Food Interactions
Rational Drug Selection
Monitoring
Patient Education
SELECTIVE SEROTONIN REUPTAKE INHIBITORS SSRIs
249
Table 15–13 " Drug Interactions: Monoamine Oxidase Inhibitors
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 249
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
250
Table 15–14 ! Pharmacokinetics: SNRIs, SSRIs, and Other Antidepressants
Drug Peak Half-Life Excretion
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosages
Rational Drug Selection
Monitoring
Patient Education
251
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252
Table 15–15 " Drug Interactions: Selective Serotonin Reuptake Inhibitors (SSRIs)
Drug Interacting Drug Possible Effect Implications
Table 15–16 # Dosage Schedule: Non-TCA Antidepressants
Drug Indications Neurotransmitters Affected Dosage
Available Dosage Forms
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253
Table 15–16 # Dosage Schedule: Non-TCA Antidepressants—cont’d
Drug Indications Neurotransmitters Affected Dosage
Available Dosage Forms
SEROTONINNOREPINEPHRINE REUPTAKE INHIBITORS SNRIs
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Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
254
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Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
ANTIPSYCHOTICS (APS)
255
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TYPICAL ANTIPSYCHOTICS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
256
Table 15–17 ! Pharmacokinetics: Typical Antipsychotics
Drug Onset Peak Duration Half-Life Excretion
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Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
257
Table 15–18 " Drug Interactions: Typical Antipsychotics
Drug Interacting Drug Possible Effect Implications
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258
Table 15–19 # Dosage Schedule: Typical Antipsychotics
Drug Indications* Available Dosage FormsDosage
3827_Ch15_225-294 02/07/15 2:48 PM Page 258
Patient Education
ATYPICAL ANTIPSYCHOTICS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
259
Table 15–20 Abnormal Involuntary Movement Scale (AIMS) Checklist
Abnormal Involuntary Movement Scale Notes
3827_Ch15_225-294 02/07/15 2:48 PM Page 259
Metabolism and Excretion
Onset, Peak, and Duration
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
260
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261
Table 15–21 " Drug Interactions: Atypical Antipsychotics
Drug Interacting Drug Possible Effect Implications
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262
Table 15–22 # Dosage Schedule: Atypical Antipsychotics
Drug Indications Dosage Available Dosage Forms
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263
Table 15–22 # Dosage Schedule: Atypical Antipsychotics—cont’d
Available Dosage Drug Indications Dosage Forms
Monitoring
Patient Education
3827_Ch15_225-294 02/07/15 2:48 PM Page 263
DOPAMINERGICS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
264
Table 15–23 ! Pharmacokinetics: Dopaminergics
Drug Onset Peak Duration Half-Life Excretion
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265
Table 15–24 " Food and Drug Interactions: Dopaminergics
Drug Interacting Drug or Food Possible Effect Implications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
3827_Ch15_225-294 02/07/15 2:48 PM Page 265
266
Table 15–25 # Dosage Schedule: Dopaminergics
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 266
Patient Education
ANXIOLYTICS (ANTIANXIETY) AND HYPNOTICS
BENZODIAZEPINES
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
267
3827_Ch15_225-294 02/07/15 2:48 PM Page 267
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
268
Table 15–26 ! Pharmacokinetics: Benzodiazepines
Drug Onset Peak Duration Half-Life Excretion
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269
Table 15–27 " Drug Interactions: Benzodiazepines
Drug Interacting Drug Possible Effect Implications
SEROTONERGIC ANXIOLYTICS
Pharmacodynamics Pharmacokinetics Absorption and Distribution
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270
Table 15–28 # Dosage Schedule: Benzodiazepines
Drugs Indications Dosage Available Dosage Forms
Metabolism and Excretion
Onset, Peak, and Duration
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reaction
3827_Ch15_225-294 02/07/15 2:48 PM Page 270
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
BARBITURATES
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
271
3827_Ch15_225-294 02/07/15 2:48 PM Page 271
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
272
Table 15–29 ! Pharmacokinetics: Barbiturates
Drug Onset Peak Duration Half-Life Excretion
Table 15–30 " Drug Interactions: Barbiturates
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 272
Rational Drug Selection
273
Table 15–31 # Dosage Schedule: Barbiturates
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 273
Monitoring
Sedative-Hypnotics
BENZODIAZEPINE HYPNOTICS
NONBENZODIAZEPINE HYPNOTICS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
274
3827_Ch15_225-294 02/07/15 2:48 PM Page 274
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
275
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MOOD STABILIZERS
LITHIUM
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Onset, Peak, and Duration
Pharmacotherapeutics Precautions and Contraindications
276
3827_Ch15_225-294 02/07/15 2:48 PM Page 276
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
277
Table 15–32 " Drug Interactions: Lithium
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 277
Monitoring
Patient Education
VALPROATES
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Onset, Peak, and Duration
Pharmacotherapeutics Precautions and Contraindications
278
Table 15–33 # Dosage Schedule: Lithium
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 278
Adverse Drug Reactions
Drug Interactions
Clinical Uses and Dosages
Rational Drug Selection
279
Table 15–34 " Drug Interactions: Valproates
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 279
Monitoring
Patient Education
NONCLASSIFIED MOOD STABILIZERS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
280
Table 15–35 # Dosage Schedule: Valproates
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 280
Drug Interactions
Clinical Use and Dosing
Rationale Drug Selection
Monitoring
Patient Education
MUSCLE RELAXANTS AND ANTISPASMOTICS
CENTRALLY ACTING MUSCLE RELAXANTS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
281
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Adverse Drug Reactions
282
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Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
283
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Monitoring
Patient Education
DIRECTACTING ANTISPASMOTICS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
284
3827_Ch15_225-294 02/07/15 2:48 PM Page 284
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
OPIOID ANALGESICS AND THEIR ANTAGONISTS
Pharmacodynamics
285
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Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
286
Table 15–36 ! Pharmacokinetics: Opioid Analgesics and Antagonists
Drug Onset Peak Duration Half-Life Excretion
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
287
Table 15–37 " Drug Interactions: Opioid Analgesics and Antagonists
Drug Interacting Drug Possible Effect Implications
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288
Table 15–38 # Dosage Schedule: Opioid Analgesics and Antagonists
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 288
Table 15–38 # Dosage Schedule: Opioid Analgesics and Antagonists—cont’d
Drug Indications Available Dosage Forms Dosage
289
3827_Ch15_225-294 02/07/15 2:48 PM Page 289
Monitoring
Patient Education
STIMULANTS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
290
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Table 15–40 " Drug Interactions: Stimulants
Drug Interacting Drug Possible Effect Implications
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
291
Table 15–39 ! Pharmacokinetics: Stimulants
Drug Onset Peak Duration Half-Life Excretion
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292
Table 15–41 # Dosage Schedule: Stimulants
Drug Indications Dosage Available Dosage Forms
Dosage
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293
Table 15–41 # Dosage Schedule: Stimulants—cont’d
Drug Indications Dosage Available Dosage Forms
Monitoring
Patient Education
REFERENCES
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294
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295
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS, ANGIOTENSIN II RECEPTOR BLOCKERS, AND DIRECT RENIN INHIBITORS
CHAPTER 16
Marylou V. Robinson
ANGIOTENSINCONVERTING ENZYME INHIBITORS, ANGIOTENSIN II RECEPTOR BLOCKERS, AND DIRECT RENIN INHIBITORS, 295 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CALCIUM CHANNEL BLOCKERS, 308 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CARDIAC GLYCOSIDES, 316 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ANTIARRHYTHMICS, 323 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
NITRATES, 333 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
PERIPHERAL VASODILATORS PADs, 338 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ANTILIPIDEMICS, 340 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
DIURETICS, 350 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
3827_Ch16_295-360 01/07/15 5:26 PM Page 295
Pharmacodynamics
296
Angiotensinogen
Renin
Angiotensin I
Potent vasoconstriction
Aldosterone
Sodium and water retention
Increased blood pressure
Adrenal gland
Angiotensin-converting enzyme
Kininogen
Kallikrein
Inactive fragments
Increased prostaglandin
synthesis
Vasodilation
Decreased blood pressure
Bradykinin Angiotensin II
Increased intravascular volume
Figure 16–1. Renin-angiotensin-aldosterone system. Renin acts on angiotensinogen to create the inactive decapeptide angiotensin I. Angiotensin I is then converted, primarily in the lung, to angiotensin II, a potent vasoconstrictor, through the activity of angiotensin-converting enzyme (ACE). Angiotensin II stimulates aldosterone secretion, causing retention of sodium and water and loss of potassium by the kidney. ACE is also involved in the inactivation of bradykinin, a vasodilator. Together, these systems help to control blood pressure.
3827_Ch16_295-360 01/07/15 5:26 PM Page 296
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
297
3827_Ch16_295-360 01/07/15 5:26 PM Page 297
298 Ta
b le
1 6–
1 !
P h
ar m
ac o
ki n
et ic
s: A
n g
io te
n si
n -C
o n
ve rt
in g
-E n
zy m
e In
h ib
it o
rs A
n g
io te
n si
n II
R ec
ep to
r B
lo ck
er s,
a n
d D
ir ec
t R
en in
In h
ib it
o rs
D u
ra ti
o n
P
ro te
in
B io
av ai
la b
il it
y Ef
fe ct
o f F
o o
d
A ct
iv e
D ru
g O
n se
t( h
) P
ea k
(h )
(h )
B in
d in
g (B
A )
o n
A b
so rp
ti o
n M
et ab
o li
te H
al f-
Li fe
(h )
El im
in at
io n
A C
E In
h ib
it o
rs
3827_Ch16_295-360 01/07/15 5:26 PM Page 298
299
A R
B s
D ir
ec t
R en
in In
h ib
it o
r
3827_Ch16_295-360 01/07/15 5:26 PM Page 299
300
Table 16–2 " Dosage Schedules: Angiotensin-Converting-Enzyme Inhibitors and Angiotensin II Receptor Blockers and Direct Renin Inhibitors
Drug Indication Dose Form Initial Dose Maintenance Dose
ACEI
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301
Table 16–2 " Dosage Schedules: Angiotensin-Converting-Enzyme Inhibitors and Angiotensin II Receptor Blockers and Direct Renin Inhibitors—cont’d
Drug Indication Dose Form Initial Dose Maintenance Dose
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302
Table 16–2 " Dosage Schedules: Angiotensin-Converting-Enzyme Inhibitors and Angiotensin II Receptor Blockers and Direct Renin Inhibitors—cont’d
Drug Indication Dose Form Initial Dose Maintenance Dose
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303
Table 16–2 " Dosage Schedules: Angiotensin-Converting-Enzyme Inhibitors and Angiotensin II Receptor Blockers and Direct Renin Inhibitors—cont’d
Drug Indication Dose Form Initial Dose Maintenance Dose
DRI
Drug Interactions
Table 16–3 # Drug Interactions: Angiotensin-Converting-Enzyme Inhibitors, Angiotensin II Receptor Antagonists, and Direct Renin Inhibitors
Drug Interacting Drug Possible Effect Implications
3827_Ch16_295-360 01/07/15 5:26 PM Page 303
Clinical Use and Dosing
304
Table 16–3 # Drug Interactions: Angiotensin-Converting-Enzyme Inhibitors, Angiotensin II Receptor Antagonists, and Direct Renin Inhibitors—cont’d
Drug Interacting Drug Possible Effect Implications
3827_Ch16_295-360 01/07/15 5:26 PM Page 304
305
Table 16–4 $ Indication and Dosage Forms: Selected ACEI and ARB Combinations
Drug Indication Dosage Form Initial Dosing Maintenance Dosing
ACEI
ARB
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306
Table 16–4 $ Indication and Dosage Forms: Selected ACEI and ARB Combinations—cont’d
Drug Indication Dosage Form Initial Dosing Maintenance Dosing
3827_Ch16_295-360 01/07/15 5:26 PM Page 306
Rational Drug Selection
Monitoring
307
CLINICAL PEARL
Many brand-name ACEIs have the same cost for dif- ferent strengths. It is possible to prescribe a high strength of the drug and have the patient halve it to achieve the desired dose, resulting in considerable cost savings.
CLINICAL PEARL
If you hear an abdominal bruit in a patient known to have vascular disease, give captopril, a short-acting ACEI, and measure serum creatinine prior to the dose and within 1 or 2 days after the dose. A rapid rise in the creatinine level suggests renal artery stenosis. A slower rise probably indicates a problem with poor hydration that can be corrected by rehydrating the patient and discontinuing or lowering the dose of any diuretics the patient is taking.
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Patient Education
CALCIUM CHANNEL BLOCKERS
Pharmacodynamics
308
CLINICAL PEARL
Patients should be monitored for indications of an- gioedema. Suspect angioedema in any patient who calls the next morning after taking the first dose and com- plains of voice changes or swollen lips or tongue. Stop the drug immediately. The symptoms recede as the drug is eliminated. Protection of the airway is rarely needed, but careful assessment of airway status is required.
3827_Ch16_295-360 01/07/15 5:26 PM Page 308
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
309
Ca2+ channels
Ca2+ channel blockers
Intracellular Ca2+ ATP
Beta2 agonists (+)
(+)
Calmodulin
Ca2+-calmodulin complex
MLCK Myosin-LC kinase MLCK-(PO4)2 Myosin
light chain
Myosin-LC-PO4 Myosin-LC
Actin
Relaxation
cAMP
Contraction
(–)
Figure 16–2. Control of smooth muscle contraction. Contraction is triggered by the influx of calcium (Ca) through transmembrane calcium channels. The calcium combines with calmodulin to form a complex that converts the enzyme myosin light-chain kinase (MLCK) to its active form. The latter phosphorylates the myosin light chains, initiating the interaction of myosin with actin that produces contraction. Relaxation begins with the reabsorption of calcium, removing it from interaction with the myosin system. Substances that increase cyclic adenosine monophosphate (cAMP), including beta agonists, may cause relaxation in smooth muscle by accelerating the inactivation of MLCK.
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310
Table 16–5 ! Pharmacokinetics: Calcium Channel Blockers
Onset Duration Protein Oral Drug (h) Peak (h) (h) Binding Bioavailability Half-Life (h) Elimination
Dihydropyridines
Type 1 CCB
Pharmacotherapeutics Precautions and Contraindications
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Adverse Drug Reactions Drug Interactions
311
Table 16–6 # Drug Interactions: Selected Calcium Channel Blockers
Drug Interacting Drug Possible Effect Implications
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312
Table 16–6 # Drug Interactions: Selected Calcium Channel Blockers—cont’d
Drug Interacting Drug Possible Effect Implications
Food Interactions
Clinical Use and Dosing
CLINICAL PEARL
Amlodipine can be crushed and put down a nasogas- tric (NG) tube, which is not possible with sustained- release preparations. This provides the clinical advantage of allowing amlodipine to act as if it were sustained-release with less venous pooling, less re- flex tachycardia, and once-daily dosing.
CLINICAL PEARL
Constipation is especially common with verapamil, with almost 100% of patients experiencing significant issues. Patients taking this drug should be encouraged to increase the fiber in their diet and may need to use a stool softener.
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313
Table 16–7 " Dosage Schedule: Selected Calcium Channel Blockers
Drug Indication Dosage Forms Starting Dose Maintenance Dose
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314
Table 16–7 " Dosage Schedule: Selected Calcium Channel Blockers—cont’d
Drug Indication Dosage Forms Starting Dose Maintenance Dose
3827_Ch16_295-360 01/07/15 5:26 PM Page 314
Rational Drug Selection
315
CLINICAL PEARL
The delivery system for nifedipine (Procardia XL) is excreted in the feces as a whole orange capsule. This does not mean that the liquid drug inside the capsule was not absorbed. To avoid alarm, the patient should be warned about this.
3827_Ch16_295-360 01/07/15 5:26 PM Page 315
Monitoring
Patient Education CARDIAC GLYCOSIDES
Pharmacodynamics Mechanical Effects on Heart Muscle
Electrical Effects on Heart Muscle
316
3827_Ch16_295-360 01/07/15 5:26 PM Page 316
Other Effects
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
317
1. Digoxin inhibits Na+/K+ pump
2. Na+ builds up in the cell
Cell membrane
4. Calcium ion increases in cell
3. Decreased gradient for Na+ to run Na+/Ca2+ transporterK
+
Na
Na
Di go
xi n
Ca pump
2Na pump
/K+
+ Na+
Na+
Na+ Na+
Na+ Ca2+ Ca2+
Ca2+
+ +
+
Figure 16–3. Effects of digoxin on the sodium–potassium pump. The sodium pump is the major determinant of the concentration of sodium in the cell. Inhibition of this pump results in sodium buildup inside the cell. The resultant decrease in sodium gradient reduces the sodium–calcium transport mechanism, and calcium ions also increase in- side the cell. The influx of sodium through voltage-gated channels is a major determinant in cardiac action poten- tials. This influx is reduced when the sodium gradient is decreased. Ultimately, contraction of cardiac muscle re- sults from the interaction of calcium with the actin–myosin system. Reduced extracellular calcium levels decrease this contraction.
Table 16–8 ! Pharmacokinetics: Cardiac Glycosides
Time to Protein Oral Steady Volume of
Drug Onset Peak Duration Binding Bioavailability Half-Life State Distribution Elimination
3827_Ch16_295-360 01/07/15 5:26 PM Page 317
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
318
3827_Ch16_295-360 01/07/15 5:26 PM Page 318
Drug Interactions
319
CLINICAL PEARL
A full neutralizing dose of Digibind is expensive (up to 20 vials at $750 per vial). This cost should be con- sidered in deciding to treat patients with suspected or non–life-threatening toxicity. It should also be re- membered that Digibind has a half-life of 2 to 6 hours, and during that time the rhythm disturbance for which the CG was given may recur and cannot be treated with a CG.
Table 16–9 # Drug Interactions: Cardiac Glycosides
Drug Interacting Drug Possible Effect Implications
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Clinical Use and Dosing
320
Table 16–9 # Drug Interactions: Cardiac Glycosides—cont’d
Drug Interacting Drug Possible Effect Implications
Food Interactions
Table 16–10 " Dosage Schedule: Cardiac Glycosides
Drug Form Indication Patient Status Digitalizing or Loading Dose Maintenance
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Rational Drug Selection
321
Table 16–10 " Dosage Schedule: Cardiac Glycosides—cont’d
Drug Form Indication Patient Status Digitalizing or Loading Dose Maintenance
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Monitoring
Patient Education
322
CLINICAL PEARL
Heart failure treatment 1. CGs should not be used unless there is clear evi-
dence of severe chronic systolic dysfunction or atrial fibrillation. In older adults, ankle edema is more often due to venous insufficiency than to heart failure. Even if it is related to heart failure, it is more often caused by diastolic dysfunction and better treated with diuretics or ACEIs.
2. Digoxin should not be discontinued unless a re- versible cause of the heart failure has been com- pletely corrected or there was no basis for the drug in the first place.
3. ST-T wave changes on the ECG do not correlate di- rectly with serum drug levels and should not be used as an indication of toxicity. Serum drug levels are needed.
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ANTIARRHYTHMICS Pharmacodynamics
323
P ha
se 0
M em
br an
e po
te nt
ia l (
m ill
iv ol
ts )
Time (milliseconds)
-100 0
ERP RRP
Phase 1
Phase 2
Phase 3
Phase 4
50 100 150 200 250
-80
-60
-40
-20
0
+20
+40
ERP: effective refractory period RRP: relative refractory period
TP: threshold potential RP: resting potential
TP
RP
Figure 16–4. Cardiac action potential: ventricles.
3827_Ch16_295-360 01/07/15 5:26 PM Page 323
Class I
Class II
Class III
324
Table 16–11 Mechanism of Action of Selected Antiarrhythmics
Effect on Effect on Effect Sinoatrial Sinoatrial Atrioventricular Node Effect on Effect on on QT Node
Drug Rate Refractory Period PR Interval QRS Duration Interval Automaticity
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Class IV
Pharmacokinetics Absorption and Distribution Metabolism and Excretion
325
Table 16–12 ! Pharmacokinetics: Selected Antiarrhythmics
Protein Active Drug Onset Peak Duration Bioavailability Binding Half-Life Metabolite Elimination
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Pharmacotherapeutics Precautions and Contraindications
326
CLINICAL PEARL
For patients with diabetes who must take a beta blocker, the diaphoresis associated with hypoglycemia is not masked by these drugs, and diabetics should be taught to recognize this indication of hypoglycemia.
3827_Ch16_295-360 01/07/15 5:26 PM Page 326
Adverse Drug Reactions Drug Interactions
327
Table 16–13 # Drug and Food Interactions: Selected Antiarrhythmics
Drug Interacting Drug/Food Possible Effect Implications
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328
Table 16–13 # Drug and Food Interactions: Selected Antiarrhythmics—cont’d
Drug Interacting Drug/Food Possible Effect Implications
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329
Table 16–13 # Drug and Food Interactions: Selected Antiarrhythmics—cont’d
Drug Interacting Drug/Food Possible Effect Implications
Clinical Use and Dosing
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Rational Drug Selection
Monitoring
330
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Patient Education
331
Table 16–14 Monitoring Parameters for Selected Antiarrhythmics
Drug Parameters Timing Comments
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332
Table 16–15 " Dosage Schedule for Selected Outpatient Labeled Uses: Selected Antiarrhythmics
Indication/Plasma Drug Concentration Dosage Forms Starting Dose Maintenance Dose
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NITRATES
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
333
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334
Nitrates Endothelial cells
Guanylyl cyclaseGuanylyl cyclase (activated)
cGMP
Myosin-LC
Relaxation
MLCK (activated)
Nitric oxide
GTP
Myosin-LC
Actin
Myosin-LC-PO4
Contraction
Figure 16–5. Action of substances that increase nitric oxide concentra- tion in smooth muscle cells. Nitrates, nitrites, and other substances that increase nitric oxide concentration in smooth muscle cells potentiate the activation of guanylyl cyclase. Acti- vated guanylyl cyclase then facilitates the production of cyclic guanosine monophosphate (cGMP). Through a series of not clearly known interme- diate steps, the cGMP facilitates the dephosphorylation of the myosin light chain, resulting in muscle relaxation.
Table 16–16 ! Pharmacokinetics: Selected Nitrates
Drug Onset Peak Duration Metabolite Half-Life Excretion
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Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
335
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336
Table 16–17 # Drug Interactions: Nitrates
Drug Interacting Drug Possible Effect Implications
Table 16–18 " Dosage Schedule: Selected Nitrates
Clinical Use Dosage Form Starting Dose Maintenance Dose
3827_Ch16_295-360 01/07/15 5:26 PM Page 336
Rational Drug Selection
Monitoring
337
CLINICAL PEARL
Patients with migraine headaches are especially at risk for nitrate headaches. Start them first on a beta blocker for migraine prophylaxis, and then add the nitrate to prevent the problem with chronic use.
3827_Ch16_295-360 01/07/15 5:26 PM Page 337
Patient Education
PERIPHERAL VASODILATORS (PADs)
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
338
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339
Table 16–19 ! Pharmacokinetics: Selected Peripheral Vasodilators
Drug Onset Peak Duration Protein Binding Bioavailability Half-Life Elimination
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Table 16–20 # Drug Interactions: Peripheral Vasodilators
Drug Interacting Drug Possible Effect Implications
3827_Ch16_295-360 01/07/15 5:26 PM Page 339
Rational Drug Selection
Monitoring
Patient Education ANTILIPIDEMICS
340
Table 16–21 " Dosage Schedule and Available Dosage Forms: Peripheral Vasodilators
Available Dosage Drug Indication Form Starting Dose Maintenance Dose
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341
On The Horizon CEPTS
Cholesterol ester transfer proteins (CEPTs) facilitate turning good HDL cholesterol into atherogenic VLDL/LDL particles. Drugs in the pipeline inhibit this protein and it is hoped that they will increase HDL levels. The REVEAL and ACELERATE clinical trials will not publish until 2016.
Pharmacodynamics
Resins
Hepatocyte Acetyl-CoA
HMG-CoA HMG-CoA reductase inhibitors
LDL
VLDL
Blood
R
Niacin Bile acids
Cholesterol
Gut
B-100
B- 10
0
Figure 16–6. Sites of action of antihyperlipidemics.
3827_Ch16_295-360 01/07/15 5:26 PM Page 341
Pharmacokinetics Absorption and Distribution
342
On The Horizon
PROPROTEIN CONVERTASE SUBTILISIN/ KESIN TYPE 9 INHIBITORS
A new biological drug class called proprotein convertase subtilisin/kesin type 9 inhibitors helps clear LDL. Studies done on statin-intolerant patients demonstrated over 50% of LDL reduction in just 12 weeks. These monoclonal antibodies do appear to have a neurological adverse side effect profile. Because they are just coming to market, they are not further covered in this chapter.
PHARMACOMETABOLICS
The new field of pharmacometabolics uses genetic and environ- mental data to inform treatment choices. The microbiome of the gut is being studied as the reason why some patients respond to statins and others do not. Bacteria modify the drug into its active metabolites. Poor responders do not have good levels of bile acids mediated by gut flora (Kaddurah-Daouk et al, 2011).
Metabolism and Excretion
On The Horizon
3827_Ch16_295-360 01/07/15 5:26 PM Page 342
343
Table 16–22 ! Pharmacokinetics: Selected Antilipidemics
Drug Onset Peak Duration Protein Binding Bioavailability Half-Life Elimination
Pharmacotherapeutics Precautions and Contraindications
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344
Table 16–23 # Drug Interactions: Selected Antilipidemics
Drug Interacting Drug Possible Effect Implications
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345
Table 16–23 # Drug Interactions: Selected Antilipidemics—cont’d
Drug Interacting Drug Possible Effect Implications
Adverse Drug Reactions
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Drug Interactions
Clinical Use and Dosing
346
Table 16–24 " Dosage Schedule: Selected Antilipidemics Labeled Uses
Drug Indication Dosage Form Starting Dose Maintenance Dose
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347
Table 16–24 " Dosage Schedule: Selected Antilipidemics Labeled Uses—cont’d
Drug Indication Dosage Form Starting Dose Maintenance Dose
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348
Table 16–24 " Dosage Schedule: Selected Antilipidemics Labeled Uses—cont’d
Drug Indication Dosage Form Starting Dose Maintenance Dose
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Rational Drug Selection
Monitoring
349
3827_Ch16_295-360 01/07/15 5:26 PM Page 349
Patient Education DIURETICS
Pharmacodynamics
350
3827_Ch16_295-360 01/07/15 5:26 PM Page 350
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
351
+
Na K2C
I
Na K2C
I
PROXIMAL CONVOLUTED TUBULE DISTAL CONVOLUTED TUBULE
Na
NaCl
Amino acids Glucose
HCO3– PO43 –
GLOMERULUS
NaCl
CORTEX
MEDULLA
Na+
PARS RECTA
Urea ASCENDING LIMB
ANP sensitive
Urea DESCENDING LIMB
H2O
H2O
Urea Passive
H2O (with ADH)
H2O no
ADH
Na KFurosemide sensitive
Aldosterone sensitive
THICK ASCENDING
LIMB
Thiazide sensitive
COLLECTING DUCT
H2O
H2O
(with ADH)
no ADH
Na
Passive
NaCl
NaCI
Organic acids
+
+
+
Figure 16–7. Sites of action of diuretics.
3827_Ch16_295-360 01/07/15 5:26 PM Page 351
Pharmacotherapeutics Precautions and Contradictions
Adverse Drug Reactions
352
Table 16–25 ! Pharmacokinetics: Selected Diuretics
Drug Onset (h) Peak (h) Duration (h) Protein Binding Bioavailability Half-Life (h) Elimination
Thiazide and Related Diuretics
Loop Diuretics
Potassium-Sparing Diuretics
3827_Ch16_295-360 01/07/15 5:26 PM Page 352
Table 16–26 # Drug Interactions: Selected Diuretics
Drug Interacting Drug Possible Effect Implications
Drug Interactions
353
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354
Table 16–26 # Drug Interactions: Selected Diuretics—cont’d
Drug Interacting Drug Possible Effect Implications
Clinical Use and Dosing
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355
Table 16–27 " Dosage Schedule: Selected Diuretics Labeled Use
Drug Indication Dosage Forms Starting Dose Maintenance Dose
3827_Ch16_295-360 01/07/15 5:26 PM Page 355
Rational Drug Selection
356
Table 16–27 " Dosage Schedule: Selected Diuretics Labeled Use—cont’d
Drug Indication Dosage Forms Starting Dose Maintenance Dose
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Monitoring
Patient Education
357
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REFERENCES
358
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359
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361
N
BRONCHODILATORS
BETA2-RECEPTOR AGONISTS
Pharmacodynamics
CHAPTER 17
Teri Moser Woo
BRONCHODILATORS, 361 BETA2RECEPTOR AGONISTS
XANTHINE DERIVATIVES
ANTICHOLINERGICS
LEUKOTRIENE MODIFIERS
RESPIRATORY INHALANTS, 384 CORTICOSTEROIDS
INHALED ANTIINFLAMMATORY AGENTS
INHALED ANTIHISTAMINES
OXYGEN
ALLERGY MEDICATIONS, 396 ANTIHISTAMINES
COUGH AND COLD MEDICATIONS, 404 DECONGESTANTS
ANTITUSSIVES
EXPECTORANTS
3827_Ch17_361-414 02/07/15 12:11 PM Page 361
Metabolism and Excretion
362
Pharmacokinetics Absorption and Distribution
3827_Ch17_361-414 02/07/15 12:11 PM Page 362
Pharmacotherapeutics Precautions and Contraindications
363
Table 17–1 ! Pharmacokinetics: Selected Bronchodilators
Drug Onset Peak Duration Half-Life Metabolism Elimination
Beta2 Agonists
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364
Table 17–1 ! Pharmacokinetics: Selected Bronchodilators—cont’d
Drug Onset Peak Duration Half-Life Metabolism Elimination
Anticholinergic
Xanthine Derivatives
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
365
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366
Table 17–2 " Drug Interactions: Selected Bronchodilators
Drug Interacting Drug Possible Effect Implications
Beta2 Agonists
3827_Ch17_361-414 02/07/15 12:11 PM Page 366
367
Table 17–2 " Drug Interactions: Selected Bronchodilators—cont’d
Drug Interacting Drug Possible Effect Implications
3827_Ch17_361-414 02/07/15 12:11 PM Page 367
368
Table 17–2 " Drug Interactions: Selected Bronchodilators—cont’d
Drug Interacting Drug Possible Effect Implications
Anticholinergics
Xanthine Derivatives
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369
3827_Ch17_361-414 02/07/15 12:11 PM Page 369
Rational Drug Selection
370
Table 17–3 # Dosage Schedule: Selected Bronchodilators
Drug Indication Dosage Form Dose Comments
Beta2 Agonists
INHALER
INHALATION SOLUTION
ORAL
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371
Table 17–3 # Dosage Schedule: Selected Bronchodilators—cont’d
Drug Indication Dosage Form Dose Comments
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372
Table 17–3 # Dosage Schedule: Selected Bronchodilators—cont’d
Drug Indication Dosage Form Dose Comments
Anticholinergics
Combination Medications
Xanthine Derivatives
IMMEDIATE-RELEASE
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Monitoring
Patient Education
373
Table 17–3 # Dosage Schedule: Selected Bronchodilators—cont’d
Drug Indication Dosage Form Dose Comments
TIMED-RELEASE
3827_Ch17_361-414 02/07/15 12:11 PM Page 373
XANTHINE DERIVATIVES
Pharmacodynamics
374
CLINICAL PEARL
Administering a medication via a nebulizer to an infant or toddler is, at times, a challenge. A pediatric mask may be used if the child tolerates it. One trick is to “blow” the nebulized medication into the patient’s face near the nose and mouth. This is achieved by occluding the mouthpiece end of the unit and aiming the “tail” end toward the patient’s nose and mouth. This is espe- cially effective if the child is sleeping and needs the medication. Another suggestion to parents of young children is to read a book to the child during the treat- ment or play an appropriate short video to make the time pass more quickly.
3827_Ch17_361-414 02/07/15 12:11 PM Page 374
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug and Food Interactions
375
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Clinical Use and Dosing
376
3827_Ch17_361-414 02/07/15 12:11 PM Page 376
Rational Drug Selection
Monitoring
Patient Education
ANTICHOLINERGICS
377
3827_Ch17_361-414 02/07/15 12:11 PM Page 377
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
378
3827_Ch17_361-414 02/07/15 12:11 PM Page 378
Drug Interactions
Clinical Use and Dosage
Rational Drug Selection
379
3827_Ch17_361-414 02/07/15 12:11 PM Page 379
Monitoring
Patient Education
LEUKOTRIENE MODIFIERS
Pharmacodynamics Leukotriene-Receptor Agonists
380
3827_Ch17_361-414 02/07/15 12:11 PM Page 380
5-Lipoxygenase Pathway Inhibitors
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
381
Table 17–4 ! Pharmacokinetics: Leukotriene Modifiers
Protein Drug Onset Peak Duration Binding Bioavailability Half-Life Metabolism Elimination
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Adverse Reactions
Drug Interactions
382
Table 17–5 " Drug Interactions: Leukotriene Modifiers
Drug Interacting Drug Possible Effect Implications
3827_Ch17_361-414 02/07/15 12:11 PM Page 382
Clinical Use and Dosing Rational Drug Selection
Monitoring
Patient Education
383
Table 17–5 " Drug Interactions: Leukotriene Modifiers—cont’d
Drug Interacting Drug Possible Effect Implications
Table 17–6 # Dosage Schedule: Leukotriene Modifiers
Drug Indication Dosage Form Dose Comments
3827_Ch17_361-414 02/07/15 12:11 PM Page 383
RESPIRATORY INHALANTS CORTICOSTEROIDS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
384
3827_Ch17_361-414 02/07/15 12:11 PM Page 384
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
385
Table 17–7 ! Pharmacokinetics: Respiratory Inhalants
Protein Drug Onset Peak Binding Bioavailability Half-Life Metabolism Elimination
Corticosteroids
Inhaled Antihistamine
Anti-Inflammatory Agents
3827_Ch17_361-414 02/07/15 12:11 PM Page 385
Adverse Reactions
Drug Interactions
Clinical Use and Dosing
386
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387
Table 17–8 " Drug Interactions: Respiratory Inhalants
Drug Interacting Drug Possible Effect Implications
Corticosteroids
Inhaled Antihistamines
Anti-Inflammatory Agents
Table 17–9 # Dosage Schedule: Respiratory Inhalants
Drug Indication Dosage Form Dose Comments
Corticosteroids
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388
Table 17–9 # Dosage Schedule: Respiratory Inhalants—cont’d
Drug Indication Dosage Form Dose Comments
3827_Ch17_361-414 02/07/15 12:11 PM Page 388
389
Table 17–9 # Dosage Schedule: Respiratory Inhalants—cont’d
Drug Indication Dosage Form Dose Comments
3827_Ch17_361-414 02/07/15 12:11 PM Page 389
390
Table 17–9 # Dosage Schedule: Respiratory Inhalants—cont’d
Drug Indication Dosage Form Dose Comments
Inhaled Antihistamine
Anti-Inflammatory Agents
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Rational Drug Selection
Monitoring
Patient Education
391
3827_Ch17_361-414 02/07/15 12:11 PM Page 391
INHALED ANTI-INFLAMMATORY AGENTS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Reactions
Drug Interactions
Clinical Use and Dosing
392
3827_Ch17_361-414 02/07/15 12:11 PM Page 392
Rational Drug Selection
Monitoring
Patient Education
INHALED ANTIHISTAMINES
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
393
3827_Ch17_361-414 02/07/15 12:11 PM Page 393
Adverse Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
OXYGEN
Pharmacodynamics
394
3827_Ch17_361-414 02/07/15 12:11 PM Page 394
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
395
3827_Ch17_361-414 02/07/15 12:11 PM Page 395
Monitoring
Patient Education
ALLERGY MEDICATIONS ANTIHISTAMINES
Pharmacodynamics
396
3827_Ch17_361-414 02/07/15 12:11 PM Page 396
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
397
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398
Table 17–10 ! Pharmacokinetics: Selected Antihistamines
Protein Drug Onset Peak Duration Binding Half-Life Metabolism Elimination
First-Generation Antihistamines
Second-Generation Antihistamines
3827_Ch17_361-414 02/07/15 12:11 PM Page 398
Adverse Drug Reactions
Drug Interactions
399
Table 17–11 " Drug Interactions: Selected Antihistamines
Drug Interacting Drug Possible Effect Implications
First-Generation Antihistamines
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400
Table 17–11 " Drug Interactions: Selected Antihistamines—cont’d
Drug Interacting Drug Possible Effect Implications
Second-Generation Antihistamines
3827_Ch17_361-414 02/07/15 12:11 PM Page 400
Clinical Use and Dosing
401
Table 17–11 " Drug Interactions: Selected Antihistamines—cont’d
Drug Interacting Drug Possible Effect Implications
Table 17–12 # Dosage Schedule: Selected Antihistamines
Drug Indication Dosage Form Dose Comments
First-Generation Antihistamines
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402
Table 17–12 # Dosage Schedule: Selected Antihistamines—cont’d
Drug Indication Dosage Form Dose Comments
Second-Generation Antihistamines
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403
Table 17–12 # Dosage Schedule: Selected Antihistamines—cont’d
Drug Indication Dosage Form Dose Comments
Rational Drug Selection
3827_Ch17_361-414 02/07/15 12:11 PM Page 403
Monitoring
Patient Education
COUGH AND COLD MEDICATIONS DECONGESTANTS
Pharmacodynamics
404
3827_Ch17_361-414 02/07/15 12:11 PM Page 404
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
405
Table 17–13 ! Pharmacokinetics: Selected Decongestants
Drug Onset Peak Duration Protein Binding Half-Life Metabolism Elimination
Systemic
Topical
3827_Ch17_361-414 02/07/15 12:11 PM Page 405
Drug Interactions
Clinical Use and Dosing
406
Table 17–14 " Drug Interactions: Selected Decongestants
Drug Interacting Drug Possible Effect Implications
Systemic
Topical
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407
Table 17–15 # Dosage Schedule: Selected Decongestants
Drug Indication Dosage Form Dose Comments
Systemic
Topical
3827_Ch17_361-414 02/07/15 12:11 PM Page 407
Rational Drug Selection
Monitoring
Patient Education
ANTITUSSIVES
Pharmacodynamics
408
3827_Ch17_361-414 02/07/15 12:11 PM Page 408
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Drug Interactions
409
Table 17–16 ! Pharmacokinetics: Selected Cough Preparations
Drug Onset Peak Duration Protein Binding Half-Life Metabolism Elimination
Expectorants
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Clinical Use and Dosing
Rational Drug Selection
Monitoring
410
Table 17–17 " Drug Interactions: Selected Cough Preparations
Drug Interacting Drug Possible Effect Implications
Antitussives
Expectorants
3827_Ch17_361-414 02/07/15 12:11 PM Page 410
Patient Education
EXPECTORANTS
411
Table 17–18 # Dosage Schedule: Selected Cough Preparations
Drug Indication Dosage Form Dose Comments
Antitussives
Expectorants
3827_Ch17_361-414 02/07/15 12:11 PM Page 411
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Effects
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
REFERENCES
412
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413
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415
CHAPTER 18
Teri Moser Woo • Kristen Osborne
ANTICOAGULANTS AND ANTIPLATELETS, 415 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
HEMATOPOIETIC GROWTH FACTORS, 430 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
IRON PREPARATIONS, 436 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
FOLIC ACID, 441 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
VITAMIN B12, 442 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
T
ANTICOAGULANTS AND ANTIPLATELETS
3827_Ch18_415_446 01/07/15 5:30 PM Page 415
416
Pharmacodynamics
Tissue factor pathway inhibitor (TFPI)
Factor VII (inhibited by oral anticoagulant
drugs, i.e., warfarin) plus tissue factor
Factor VIIa (inhibited by heparin) minus tissue factor
Factor XIa (downregulated by protein C act)
Factor IX (inhibited by oral anticoagulant
drugs, i.e., warfarin)
Factor IXa (inhibited by heparin)
Factor VIIIa (downregulated by protein C act)
Factor X (inhibited by oral anticoagulant drugs,
i.e., warfarin)
Factor Xa (inhibited by heparin)
Factor Va (downregulated by protein C act)
Factor II—Prothrombin (inhibited by oral anticoagulant
drugs, i.e., warfarin)
Factor IIa—Thrombin (inhibited by heparin)
Factor I—Fibrinogen Factor Ia—Fibrin clot
Figure 18–1. The clotting cascade.
On The Horizon IDRABIOTAPARINUX
Idraparinux is an analog of fondaparinux given once a week, but trials were discontinued due to excessive bleeding. Idra- biotaparinux is a biotinylated version of idraparinux that is currently being studied for treatment of pulmonary embolism and is as effective as warfarin with less bleeding (Büller et al. 2012). Idrabiotaparinux is also being studied for prophylaxis treatment of DVT (Equinox Investigators, 2011).
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Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
417
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418
Table 18–1 ! Pharmacokinetics: Selected Anticoagulants and Antiplatelets
Drug
Anticoagulants
Antiplatelets
Du ration Protein Binding
Bioavailability/ Volume of Distribution Half-Life EliminationPeakOnset
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Pharmacotherapeutics Precautions and Contraindications
419
3827_Ch18_415_446 01/07/15 5:30 PM Page 419
Adverse Drug Reactions
420
3827_Ch18_415_446 01/07/15 5:30 PM Page 420
Drug Interactions
421
CLINICAL PEARL
To maintain anticoagulation in patients with allergic reactions to warfarin, enoxaparin or fondaparinux can be given SC long term. The usual dose is 1 mg/kg.
Table 18–2 " Drug Interactions: Selected Anticoagulants and Antiplatelets
Drug Interacting Drug Possible Effect Implications
Anticoagulants
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422
Table 18–2 " Drug Interactions: Selected Anticoagulants and Antiplatelets—cont’d
Drug Interacting Drug Possible Effect Implications
Antiplatelets
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423
Table 18–2 " Drug Interactions: Selected Anticoagulants and Antiplatelets—cont’d
Drug Interacting Drug Possible Effect Implications
Clinical Use and Dosing
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424
3827_Ch18_415_446 01/07/15 5:30 PM Page 424
425
Table 18–3 # Dosage Schedule: Selected Anticoagulants and Antiplatelets
Drug Indication Dosage Form Initial Dose Maintenance Dose
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426
Table 18–3 # Dosage Schedule: Selected Anticoagulants and Antiplatelets—cont’d
Drug Indication Dosage Form Initial Dose Maintenance Dose
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427
Table 18–4 Recommended INR Values Based on Reason for Warfarin Use
Reason for Use INR range
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Rational Drug Selection
Monitoring
428
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Patient Education: Anticoagulants
429
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Patient Education: Antiplatelets
HEMATOPOIETIC GROWTH FACTORS
Pharmacodynamics
430
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Pharmacokinetics Absorption and Distribution
431
Myeloid stem cell
Megakaryoblast
Promegakaryocyte
Megakaryocyte
Monoblast
Promonocyte
Pronormoblast
Basophilic normoblast
Polychromatic normoblast
Orthochromatic normoblast
Red blood cell
Basophil precursor
Mature basophil
Monocyte
Myeloblast type I
Myeloblast type II
Eosinophil precursor
Promyelocyte Mature eosinophil
Neutrophil myelocyte
Neutrophil metamyelocyte
Neutrophil band
Segmented neutrophil
Granulocyte- macrophage colony-
stimulating factor (GM-CSF)
Erythropoietin
Granulocyte-macrophage colony-stimulating
factor (GM-CSF)
= Controlling factor in cell differentiation in each cell line
Thrombopoietin (Erythropoietin)
Granulocyte colony-stimulating factor (G-CSF)
Granulocyte-macrophage colony- stimulating factor (GM-CSF)
Figure 18–2. Development of blood cells.
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432
Table 18–5 ! Pharmacokinetics: Hematopoietic Growth Factors
Drug Onset Peak Duration Half-Life
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
433
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434
Table 18–6 " Drug Interactions: Hematopoietic Growth Factors
Drug Interacting Drug Possible Effect Implications
Table 18–7 # Dosage Schedule: Hematopoietic Growth Factors
Drug Indication Initial Dose Maintenance Dose
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435
Rational Drug Selection
Monitoring
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Patient Education
IRON PREPARATIONS
436
Table 18–8 $ Available Dosage Forms: Hematopoietic Growth Factors
Drug Dosage Form Other Forms Cost
3827_Ch18_415_446 01/07/15 5:30 PM Page 436
Pharmacodynamics
437
Mature erythrocytes (from the bone marrow)
Circulate in the blood- stream (about 120 days)
Aged, damaged, or abnormal erythrocytes (removed by the
macrophages of the mononuclear phagocyte system [MPS])
Macrophages of the MPS in the spleen, liver, and bone marrow
break down the erythrocytes
Hemoglobin
Heme
Iron
Iron released from the gastrointestinal epithelial cells
Circulates with its plasma carrier, transferrin
Returned directly to the bloodstream
Secreted with bile
Globin
Iron reused (to synthesize new hemoglobin) by the erythroblasts in the bone marrow
Bilirubin
Stored in the liver
Released from the liver into the bloodstream
Stored in the spleen
Released from the spleen into the bloodstream
Figure 18–3. The iron cycle.
On The Horizon
INTERLEUKIN-3, STEM CELL FACTOR, AND MONOCYTE-MACROPHAGE COLONY–STIMULATING FACTOR
IL-3, stem cell factor, and monocyte-macrophage colony– stimulating factor are currently in clinical trials. IL-3 would provide broad-based therapy because it is involved in the generation and stimulation of all progenitor cells. Stem cell factor would provide therapy at an even earlier stage in blood cell development. Monocyte-macrophage colony–stimulating factor would provide a targeted approach to patients who do not require such a broad stimulation of blood cell growth.
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Pharmacokinetics Absorption and Distribution
Metabolism, Storage, and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
438
3827_Ch18_415_446 01/07/15 5:30 PM Page 438
Rational Drug Selection
Monitoring
Patient Education
439
Table 18–9 " Drug Interactions: Iron
Drug Interacting Drug Possible Effect Implications
3827_Ch18_415_446 01/07/15 5:30 PM Page 439
440
Table 18–10 # Dosage Schedule: Iron
Drug Indication Dosage Form Maintenance Dose
3827_Ch18_415_446 01/07/15 5:30 PM Page 440
FOLIC ACID
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism, Storage, and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
441
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442
Table 18–11 " Drug Interactions: Folic Acid
Drug Interacting Drug Possible Effect Implications
Table 18–12 # Dosage Schedule: Folic Acid
Drug Indication Initial Dose Maintenance Dose
Rational Drug Selection
Monitoring
Patient Education
VITAMIN B12
Pharmacodynamics
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Pharmacokinetics Absorption and Distribution
Metabolism, Storage, and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
443
Table 18–13 $ Available Dosage Forms: Folic Acid
Drug Dosage Form Other Forms Cost
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444
Table 18–14 " Drug Interactions: Vitamin B12 Drug Interacting Drug Possible Effect Implications
Table 18–15 # Dosage Schedule: Vitamin B12 Drug Indication Initial Dose Maintenance Dose
3827_Ch18_415_446 01/07/15 5:30 PM Page 444
Rational Drug Selection
Monitoring
Patient Education
445
Table 18–16 $ Available Dosage Forms: Vitamin B12 Drug Dosage Form How Supplied Cost
3827_Ch18_415_446 01/07/15 5:30 PM Page 445
REFERENCES
446
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447
CHAPTER 19
Teri Moser Woo
IMMUNIZATIONS
ATTENUATED VACCINES, 448 INFLUENZA LIVE, ATTENUATED INFLUENZA VACCINE
MEASLES, MUMPS, AND RUBELLA VACCINE
MEASLES, MUMPS, RUBELLA, AND VARICELLA VACCINE
ORAL POLIOVIRUS VACCINE
ROTAVIRUS VACCINE
VARICELLA VIRUS VACCINE
ZOSTER VACCINE
ORAL TYPHOID VACCINE
YELLOW FEVER VACCINE
BACILLUS CALMETTEGUÉRIN VACCINE
INACTIVATED VACCINES, 471 DIPHTHERIA, TETANUS, AND PERTUSSIS VACCINE
B CONJUGATE VACCINE
INACTIVATED POLIOVIRUS VACCINE
HEPATITIS B VIRUS VACCINE
HEPATITIS A VIRUS VACCINE
HUMAN PAPILLOMAVIRUS VACCINE
INFLUENZA VACCINE
PNEUMOCOCCAL VACCINE
MENINGOCOCCAL VACCINE
LYME DISEASE VACCINE
TYPHOID VACCINE
CHOLERA VACCINE
JAPANESE ENCEPHALITIS VIRUS VACCINE
PLAGUE VACCINE
RABIES VACCINE
IMMUNE GLOBULIN SERUMS
DIAGNOSTIC BIOLOGICALS, 490 TUBERCULIN PURIFIED PROTEIN DERIVATIVE
IMMUNOMODULATORS
P
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448
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
IMMUNIZATIONS
ATTENUATED VACCINES INFLUENZA LIVE, ATTENUATED INFLUENZA VACCINE
Pharmacodynamics
3827_Ch19_447_496 02/07/15 12:05 PM Page 448
Clinical Use and Dosing
Monitoring
Patient Education
MEASLES, MUMPS, AND RUBELLA VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
449
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
450
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451
Fi gu
re 1
. R ec
om m
en de
d im
m un
iz at
io n
sc he
du le
fo r p
er so
ns a
ge d
0 th
ro ug
h 18
y ea
rs –
U ni
te d
St at
es , 2
01 5.
(F O
R TH
O SE
W H
O F
A LL
B EH
IN D
O R
ST A
RT L
AT E,
S EE
T H
E C
AT CH
-U P
SC H
ED U
LE [F
IG U
RE 2
]) .
Th es
e re
co m
m en
da tio
ns m
us t b
e re
ad w
ith th
e fo
ot no
te s
th at
fo llo
w . F
or th
os e
w ho
fa ll
be hi
nd o
r s ta
rt la
te , p
ro vi
de c
at ch
-u p
va cc
in at
io n
at th
e ea
rli es
t o pp
or tu
ni t y
a s
in di
ca te
d by
th e
gr ee
n ba
rs in
F ig
ur e
1.
To d
et er
m in
e m
in im
um in
te rv
al s
be tw
ee n
do se
s, s
ee th
e ca
tc h-
up s
ch ed
ul e
(F ig
ur e
2) . S
ch oo
l e nt
ry a
nd a
do le
sc en
t v ac
ci ne
a ge
g ro
up s
ar e
sh ad
ed .
N O
TE : T
he a
bo ve
re co
m m
en da
ti on
s m
us t b
e re
ad a
lo ng
w it
h th
e fo
ot no
te s
of th
is s
ch ed
ul e.
Th is
s ch
ed ul
e in
cl ud
es re
co m
m en
da tio
ns in
e ff
ec t a
s of
J an
ua ry
1 , 2
01 5.
A ny
d os
e no
t a dm
in is
te re
d at
th e
re co
m m
en de
d ag
e sh
ou ld
b e
ad m
in is
te re
d at
a s
ub se
qu en
t v is
it, w
he n
in di
ca te
d an
d fe
as ib
le . T
he u
se o
f a c
om b
in at
io n
va cc
in e
ge ne
ra lly
is p
re fe
rr ed
o ve
r s ep
ar at
e in
je ct
io ns
o f i
ts e
qu iv
al en
t c om
po ne
nt v
ac ci
ne s.
V ac
ci na
tio n
pr ov
id er
s sh
ou ld
c on
su lt
th e
re le
va nt
A dv
is or
y C
om m
itt ee
on
Im m
un iz
at io
n Pr
ac tic
es (A
C IP
) s ta
te m
en t f
or d
et ai
le d
re co
m m
en da
tio ns
, a va
ila bl
e on
lin e
at h
tt p:
// w
w w
.c dc
.g ov
/v ac
ci ne
s/ hc
p/ ac
ip -r
ec s/
in de
x. ht
m l.
C lin
ic al
ly s
ig ni
fic an
t a dv
er se
e ve
nt s
th at
fo llo
w
va cc
in at
io n
sh ou
ld b
e re
p or
te d
to th
e Va
cc in
e A
dv er
se E
ve nt
R ep
or tin
g Sy
st em
(V A
ER S)
o nl
in e
(h tt
p: //
w w
w .v
ae rs
.h hs
.g ov
) o r b
y te
le p
ho ne
(8 00
-8 22
-7 96
7) . S
us p
ec te
d ca
se s
of v
ac ci
ne -p
re ve
nt ab
le
di se
as es
s ho
ul d
be re
po rt
ed to
th e
st at
e or
lo ca
l h ea
lth d
ep ar
tm en
t. A
dd iti
on al
in fo
rm at
io n,
in cl
ud in
g pr
ec au
tio ns
a nd
c on
tr ai
nd ic
at io
ns fo
r v ac
ci na
tio n,
is a
va ila
bl e
fr om
C D
C o
nl in
e
(h tt
p: //
w w
w .c
dc .g
ov /v
ac ci
ne s/
re cs
/v ac
-a dm
in /c
on tr
ai nd
ic at
io ns
.h tm
) o r b
y te
le p
ho ne
(8 00
-C D
C -IN
FO [8
00 -2
32 -4
63 6]
). Th
is s
ch ed
ul e
is a
p p
ro ve
d by
th e
A dv
is or
y C
om m
itt ee
o n
Im m
un iz
at io
n Pr
ac tic
es (h
tt p/
/w w
w .c
dc .g
ov /v
ac ci
ne s/
ac ip
), th
e A
m er
ic an
A ca
de m
y of
P ed
ia tr
ic s
(h tt
p: //
w w
w .a
ap .o
rg ),
th e
A m
er ic
an A
ca de
m y
of
Fa m
ily P
hy si
ci an
s (h
tt p:
// w
w w
.a af
p. or
g) , a
nd th
e A
m er
ic an
C ol
le ge
o f O
b st
et ric
ia ns
a nd
G yn
ec ol
og is
ts (h
tt p:
// w
w w
.a co
g. or
g) .
N ot
ro ut
in el
y re
co m
m en
de d
Ra ng
e of
re co
m m
en de
d ag
es fo
r ce
rt ai
n hi
gh -r
is k
g ro
up s
Ra ng
e of
re co
m m
en de
d ag
es fo
r a ll
ch ild
re n
Ra ng
e of
re co
m m
en de
d ag
es
fo r c
at ch
-u p
im m
un iz
at io
n Ra
ng e
of re
co m
m en
de d
ag es
d ur
in g
w hi
ch c
at ch
-u p
is e
nc ou
ra ge
d an
d fo
r ce
rt ai
n hi
gh -r
is k
gr ou
p s
Va cc
in e
Bi rt
h 1
m o
2 m
os 4
m os
6 m
os 9
m os
12 m
os 15
m os
18 m
os 19
–2 3
m os
2- 3
yr s
4- 6
yr s
7- 10
y rs
11 -1
2 yr
s 13
–1 5
yr s
16 –1
8 yr
s
H ep
at iti
s B1
(H ep
B)
Ro ta
vi ru
s2 (R
V ) R
V1 (2
-d os
e se
rie s)
; R V5
(3 -d
os e
se rie
s)
D ip
ht he
ria , t
et an
us , &
a ce
llu la
r pe
rt us
si s3
(D Ta
P: <
7 yr
s)
Te ta
nu s,
di ph
th er
ia , &
a ce
llu la
r pe
rt us
si s4
(T da
p: >
7 yr
s)
ty pe
b 5
(H ib
)
Pn eu
m oc
oc ca
l c on
ju ga
te 6
(P C
V1 3)
Pn eu
m oc
oc ca
l p ol
ys ac
ch ar
id e6
(P
PS V2
3)
In ac
tiv at
ed p
ol io
vi ru
s7
(IP V:
< 18
y rs
)
8 ( IIV
; L A
IV )
2 do
se s
fo r
so m
e: S
ee fo
ot no
te 8
M ea
sl es
, m um
ps , r
ub el
la 9 (
M M
R)
Va ric
el la
10 (V
A R)
H ep
at iti
s A
11 (H
ep A
)
H um
an p
ap ill
om av
iru s1
2 ( H
PV 2:
fe
m al
es o
nl y;
H PV
4: m
al es
a nd
fe
m al
es )
M en
in go
co cc
al 13
(H ib
-M en
CY
> 6
w ee
ks ; M
en A
C W
Y- D
> 9
m os
; M
en A
C W
Y- CR
M ≥
2 m
os )
Bo os
te r
1s t d
os e
Se e
fo ot
no te
1 3
(3 -d
os e
se rie
s)
A nn
ua l v
ac ci
na tio
n (L
A IV
o r
IIV ) 1
o r 2
d os
es A
nn ua
l v ac
ci na
tio n
(II V
on ly
) 1 o
r 2 d
os es
(T da
p)
Se e
fo ot
no te
2 2n
d d os
e 1s
t d os
e
4t h d
os e
3r d d
os e
2n d d
os e
1s t d
os e
2- do
se s
er ie
s, S
ee fo
ot no
te 1
1
4t h d
os e
3r d d
os e
2n d
do se
1s t d
os e
2n d
do se
1s t d
os e
3r d o
r 4 th
d os
e,
Se e
fo ot
no te
5 Se
e fo
ot no
te 5
2n d
do se
1s t d
os e
2n d
do se
1s t d
os e
5t h d
os e
4t h d
os e
3r d d
os e
2n d d
os e
1s t d
os e
3r d d
os e
2n d d
os e
1s t d
os e
A nn
ua l v
ac ci
na tio
n (L
A IV
o r I
IV )
1 do
se o
nl y
Se e
fo ot
no te
9
Ta b
le 1
9– 1 !
R ec
o m
m en
d ed
Im m
u n
iz at
io n
S ch
ed u
le fo
r P
er so
n s
A g
ed 0
T h
ro u
g h
18 Y
ea rs
— U
n it
ed S
ta te
s, 2
01 5
3827_Ch19_447_496 02/07/15 12:05 PM Page 451
452 Ta
b le
1 9–
1 !
R ec
o m
m en
d ed
Im m
u n
iz at
io n
S ch
ed u
le fo
r P
er so
n s
A g
ed 0
T h
ro u
g h
18 Y
ea rs
— U
n it
ed S
ta te
s, 2
01 5—
co n
t’ d
Fo ot
no te
s —
R ec
om m
en de
d im
m un
iz at
io n
sc he
du le
fo r p
er so
ns a
ge d
0 th
ro ug
h 18
y ea
rs —
U ni
te d
St at
es , 2
01 5
Fo
r f ur
th er
g ui
da nc
e on
th e
us e
of th
e va
cc in
es m
en tio
ne d
be lo
w , s
ee : h
tt p:
// w
w w
.c dc
.g ov
/v ac
ci ne
s/ hc
p/ ac
ip -r
ec s/
in de
x. ht
m l.
Fo
r v ac
ci ne
re co
m m
en da
tio ns
fo r p
er so
ns 1
9 ye
ar s
of a
ge a
nd o
ld er
, s ee
th e
A du
lt Im
m un
iz at
io n
Sc he
du le
. A
d d
it io
na l i
nf or
m at
io n
• Fo
r c on
tr ai
nd ic
at io
ns a
nd p
re ca
ut io
ns to
u se
o f a
v ac
ci ne
a nd
fo r a
dd iti
on al
in fo
rm at
io n
re ga
rd in
g th
at v
ac ci
ne , v
ac ci
na tio
n pr
ov id
er s
sh ou
ld c
on su
lt th
e re
le va
nt A
C IP
s ta
te m
en t a
va ila
bl e
on lin
e at
ht
tp ://
w w
w .c
dc .g
ov /v
ac ci
ne s/
hc p/
ac ip
-r ec
s/ in
de x.
ht m
l. •
Fo r p
ur po
se s
of c
al cu
la tin
g in
te rv
al s
be tw
ee n
do se
s, 4
w ee
ks =
2 8
da ys
. I nt
er va
ls o
f 4 m
on th
s or
g re
at er
a re
d et
er m
in ed
b y
ca le
nd ar
m on
th s.
• Va
cc in
e do
se s
ad m
in is
te re
d 4
da ys
o r l
es s
be fo
re th
e m
in im
um in
te rv
al a
re c
on si
de re
d va
lid . D
os es
o f a
ny v
ac ci
ne a
dm in
is te
re d
≥ 5
da ys
e ar
lie r t
ha n
th e
m in
im um
in te
rv al
o r m
in im
um a
ge s
ho ul
d no
t be
c ou
nt ed
a s
va lid
d os
es a
nd s
ho ul
d be
re pe
at ed
a s
ag e-
ap pr
op ria
te . T
he re
pe at
d os
e sh
ou ld
b e
sp ac
ed a
ft er
th e
in va
lid d
os e
by th
e re
co m
m en
de d
m in
im um
in te
rv al
. F or
fu rt
he r d
et ai
ls , s
ee M
M W
R,
G en
er al
R ec
om m
en da
tio ns
o n
Im m
un iz
at io
n an
d Re
po rt
s / V
ol . 6
0 / N
o. 2
; T ab
le 1
. R ec
om m
en de
d an
d m
in im
um a
ge s a
nd in
te rv
al s b
et w
ee n
va cc
in e
do se
s a va
ila bl
e on
lin e
at
ht tp
:// w
w w
.c dc
.g ov
/m m
w r/
pd f/
rr /r
r6 00
2. pd
f. •
In fo
rm at
io n
on tr
av el
v ac
ci ne
re qu
ire m
en ts
a nd
re co
m m
en da
tio ns
is a
va ila
bl e
at h
tt p:
// w
w w
nc .c
dc .g
ov /t
ra ve
l/d es
tin at
io ns
/li st
. •
in G
en er
al R
ec om
m en
da tio
ns o
n Im
m un
iz at
io n
(A C
IP ),
av ai
la bl
e at
h tt
p: //
w w
w .c
dc .g
ov /m
m w
r/ pd
f/ rr
/r r6
00 2.
pd f.;
a nd
A m
er ic
an A
ca de
m y
of P
ed ia
tr ic
s. “I
m m
un iz
at io
n in
S pe
ci al
C lin
ic al
C irc
um st
an ce
s ,” in
P ic
ke rin
g LK
, B ak
er C
J, Ki
m be
rli n
D W
, L on
g SS
e ds
. R ed
B oo
k: 2
01 2
re po
rt o
f t he
C om
m itt
ee o
n In
fe ct
io us
D is
ea se
s. 29
th e
d. E
lk G
ro ve
V ill
ag e,
IL : A
m er
ic an
A ca
de m
y of
P ed
ia tr
ic s.
1.
H ep
at it
is B
(H ep
B) v
ac ci
ne . (
M in
im um
a ge
: b ir
th )
Ro ut
in e
va cc
in at
io n:
A
t b ir
th :
• A
dm in
is te
r m on
ov al
en t H
ep B
va cc
in e
to a
ll ne
w bo
rn s
be fo
re h
os pi
ta l d
is ch
ar ge
. •
Fo r i
nf an
ts b
or n
to h
ep at
iti s
B su
rf ac
e an
tig en
(H Bs
A g)
-p os
iti ve
m ot
he rs
, a dm
in is
te r H
ep B
va cc
in e
an d
0. 5
m L
of h
ep at
iti s
B im
m un
e gl
ob ul
in (H
BI G
) w ith
in 1
2 ho
ur s
of b
irt h.
T he
se in
fa nt
s sh
ou ld
b e
te st
ed
fo r H
Bs A
g an
d an
tib od
y to
H Bs
A g
(a nt
i-H Bs
) 1 to
2 m
on th
s af
te r c
om pl
et io
n of
th e
H ep
B se
rie s
at a
ge 9
th
ro ug
h 18
m on
th s
(p re
fe ra
bl y
at th
e ne
xt w
el l-c
hi ld
v is
it) .
• If
m ot
he r’s
H Bs
A g
st at
us is
u nk
no w
n, w
ith in
1 2
ho ur
s of
b irt
h ad
m in
is te
r H ep
B va
cc in
e re
ga rd
le ss
o f b
irt h
w ei
gh t.
Fo r i
nf an
ts w
ei gh
in g
le ss
th an
2 ,0
00 g
ra m
s, a
dm in
is te
r H BI
G in
a dd
iti on
to H
ep B
va cc
in e
w ith
in
12 h
ou rs
o f b
irt h.
D et
er m
in e
m ot
he r’s
H Bs
A g
st at
us a
s so
on a
s po
ss ib
le a
nd , i
f m ot
he r i
s H
Bs A
g- po
si tiv
e,
al so
a dm
in is
te r H
BI G
fo r i
nf an
ts w
ei gh
in g
2, 00
0 gr
am s
or m
or e
as s
oo n
as p
os si
bl e,
b ut
n o
la te
r t ha
n ag
e 7
da ys
. D
os es
fo llo
w in
g th
e bi
rt h
do se
: •
Th e
se co
nd d
os e
sh ou
ld b
e ad
m in
is te
re d
at a
ge 1
o r 2
m on
th s.
M on
ov al
en t H
ep B
va cc
in e
sh ou
ld b
e us
ed fo
r d os
es a
dm in
is te
re d
be fo
re a
ge 6
w ee
ks .
• In
fa nt
s w
ho d
id n
ot re
ce iv
e a
bi rt
h do
se s
ho ul
d re
ce iv
e 3
do se
s of
a H
ep B-
co nt
ai ni
ng v
ac ci
ne o
n a
sc he
du le
o f 0
, 1 to
2 m
on th
s, a
nd 6
m on
th s
st ar
tin g
as s
oo n
as fe
as ib
le . S
ee F
ig ur
e 2.
• th
e th
ird d
os e
at le
as t 8
w ee
ks a
ft er
th e
se co
nd d
os e
A N
D a
t l ea
st 1
6 w
ee ks
a ft
er th
e (t
hi rd
o r f
ou rt
h) d
os e
in th
e H
ep B
va cc
in e
se rie
s sh
ou ld
b e
ad m
in is
te re
d no
e ar
lie r t
ha n
ag e
24 w
ee ks
. •
A dm
in is
tr at
io n
of a
to ta
l o f 4
d os
es o
f H ep
B va
cc in
e is
p er
m itt
ed w
he n
a co
m bi
na tio
n va
cc in
e co
nt ai
ni ng
H
ep B
is a
dm in
is te
re d
af te
r t he
b irt
h do
se .
Ca tc
h- up
v ac
ci na
ti on
: •
U nv
ac ci
na te
d pe
rs on
s sh
ou ld
c om
pl et
e a
3- do
se s
er ie
s. •
A 2
-d os
e se
rie s
(d os
es s
ep ar
at ed
b y
at le
as t 4
m on
th s)
o f a
du lt
fo rm
ul at
io n
Re co
m bi
va x
H B
is li
ce ns
ed fo
r us
e in
c hi
ld re
n ag
ed 1
1 th
ro ug
h 15
y ea
rs .
• Fo
r o th
er c
at ch
-u p
gu id
an ce
, s ee
F ig
ur e
2. 2.
Ro
ta vi
ru s
(R V
) v ac
ci ne
s. (M
in im
um a
ge : 6
w ee
ks fo
r b ot
h RV
1 [R
ot ar
ix ] a
nd
RV 5
[R ot
aT eq
]) Ro
ut in
e va
cc in
at io
n: A
dm in
is te
r a s
er ie
s of
R V
va cc
in e
to a
ll in
fa nt
s as
fo llo
w s:
1.
I f R
ot ar
ix is
u se
d, a
dm in
is te
r a 2
-d os
e se
rie s
at 2
a nd
4 m
on th
s of
a ge
. 2.
I f R
ot aT
eq is
u se
d, a
dm in
is te
r a 3
-d os
e se
rie s
at a
ge s
2, 4
, a nd
6 m
on th
s.
3. I
f a ny
d os
e in
th e
se rie
s w
as R
ot aT
eq o
r v ac
ci ne
p ro
du ct
is u
nk no
w n
fo r a
ny d
os e
in th
e se
rie s,
a to
ta l o
f 3
do se
s of
R V
va cc
in e
sh ou
ld b
e ad
m in
is te
re d.
Ca
tc h-
up v
ac ci
na ti
on :
• fo
r i nf
an ts
a ge
d 15
w ee
ks , 0
d ay
s or
o ld
er .
• • Fo
r o th
er c
at ch
-u p
gu id
an ce
, s ee
F ig
ur e
2. 3.
D
ip ht
he ri
a an
d te
ta nu
s to
xo id
s an
d ac
el lu
la r p
er tu
ss is
(D Ta
P) v
ac ci
ne . (
M in
im um
ag
e: 6
w ee
ks . E
xc ep
ti on
: D Ta
P- IP
V [K
in ri
x] : 4
y ea
rs )
Ro ut
in e
va cc
in at
io n:
• A
dm in
is te
r a 5
-d os
e se
rie s
of D
Ta P
va cc
in e
at a
ge s
2, 4
, 6 , 1
5 th
ro ug
h 18
m on
th s,
a nd
4 th
ro ug
h 6
ye ar
s.
Th e
fo ur
th d
os e
m ay
b e
ad m
in is
te re
d as
e ar
ly a
s ag
e 12
m on
th s,
p ro
vi de
d at
le as
t 6 m
on th
s ha
ve e
la ps
ed
si nc
e th
e th
ird d
os e.
H ow
ev er
, t he
fo ur
th d
os e
of D
Ta P
ne ed
n ot
b e
re pe
at ed
if it
w as
a dm
in is
te re
d at
le
as t 4
m on
th s
af te
r t he
th ird
d os
e of
D Ta
P.
3.
D ip
ht he
ri a
an d
te ta
nu s
to xo
id s
an d
ac el
lu la
r p er
tu ss
is (D
Ta P)
v ac
ci ne
(c on
t’d )
Ca tc
h- up
v ac
ci na
ti on
: • •
Fo r o
th er
c at
ch -u
p gu
id an
ce , s
ee F
ig ur
e 2.
4.
Te ta
nu s
an d
di ph
th er
ia to
xo id
s an
d ac
el lu
la r p
er tu
ss is
(T da
p) v
ac ci
ne . (
M in
im um
ag
e: 1
0 ye
ar s
fo r b
ot h
Bo os
tr ix
a nd
A da
ce l)
Ro ut
in e
va cc
in at
io n:
•
A dm
in is
te r 1
d os
e of
T da
p va
cc in
e to
a ll
ad ol
es ce
nt s
ag ed
1 1
th ro
ug h
12 y
ea rs
. •
Td ap
m ay
b e
ad m
in is
te re
d re
ga rd
le ss
o f t
he in
te rv
al s
in ce
th e
la st
te ta
nu s
an d
di ph
th er
ia to
xo id
- co
nt ai
ni ng
v ac
ci ne
. •
A dm
in is
te r 1
d os
e of
T da
p va
cc in
e to
p re
gn an
t a do
le sc
en ts
d ur
in g
ea ch
p re
gn an
cy (p
re fe
rr ed
d ur
in g
27
th ro
ug h
36 w
ee ks
’ g es
ta tio
n) re
ga rd
le ss
o f t
im e
si nc
e pr
io r T
d or
T da
p va
cc in
at io
n.
Ca tc
h- up
v ac
ci na
ti on
: •
Pe rs
on s
ag ed
7 y
ea rs
a nd
o ld
er w
ho a
re n
ot fu
lly im
m un
iz ed
w ith
D Ta
P va
cc in
e sh
ou ld
re ce
iv e
Td ap
va cc
in e.
F or
c hi
ld re
n 7
th ro
ug h
10 y
ea rs
w ho
re ce
iv e
a do
se o
f T da
p as
p ar
t o f t
he c
at ch
-u p
se rie
s, a
n ad
ol es
ce nt
T da
p va
cc in
e do
se a
t a ge
1 1
th ro
ug h
12 y
ea rs
s ho
ul d
N O
T be
a dm
in is
te re
d. T
d sh
ou ld
b e
ad m
in is
te re
d in
st ea
d 10
y ea
rs a
ft er
th e
Td ap
d os
e. •
Pe rs
on s
ag ed
1 1
th ro
ug h
18 y
ea rs
w ho
h av
e no
t r ec
ei ve
d Td
ap v
ac ci
ne s
ho ul
d re
ce iv
e a
do se
fo llo
w ed
b y
te ta
nu s
an d
di ph
th er
ia to
xo id
(T d)
b oo
st er
d os
es e
ve ry
1 0
ye ar
s th
er ea
ft er
. •
In ad
ve rt
en t d
os es
o f D
Ta P
va cc
in e:
- If
ad m
in is
te re
d in
ad ve
rt en
tly to
a c
hi ld
a ge
d 7
th ro
ug h
10 y
ea rs
m ay
c ou
nt a
s pa
rt o
f t he
c at
ch -u
p se
rie s.
T hi
s do
se m
ay c
ou nt
a s
th e
ad ol
es ce
nt T
da p
do se
, o r t
he c
hi ld
c an
la te
r r ec
ei ve
a T
da p
bo os
te r
do se
a t a
ge 1
1 th
ro ug
h 12
y ea
rs .
- If
ad m
in is
te re
d in
ad ve
rt en
tly to
a n
ad ol
es ce
nt a
ge d
11 th
ro ug
h 18
y ea
rs , t
he d
os e
sh ou
ld b
e co
un te
d as
th e
ad ol
es ce
nt T
da p
bo os
te r.
• Fo
r o th
er c
at ch
-u p
gu id
an ce
, s ee
F ig
ur e
2. 5.
ty
pe b
(H ib
) c on
ju ga
te v
ac ci
ne .
(M in
im um
a ge
: 6
w ee
ks
fo r P
RP -T
[A C
TH IB
, D Ta
P- IP
V /H
ib (P
en ta
ce l)
an d
H ib
-M en
C Y
(M en
H ib
ri x)
], PR
P- O
M P
[P ed
va xH
IB o
r C O
M VA
X ],
12 m
on th
s fo
r P RP
-T [H
ib er
ix ])
Ro
ut in
e va
cc in
at io
n: •
A dm
in is
te r a
2 - o
r 3 -d
os e
H ib
v ac
ci ne
p rim
ar y
se rie
s an
d a
bo os
te r d
os e
(d os
e 3
or 4
d ep
en di
ng o
n va
cc in
e us
ed in
p rim
ar y
se rie
s) a
t a ge
1 2
th ro
ug h
15 m
on th
s to
c om
pl et
e a
fu ll
H ib
v ac
ci ne
s er
ie s.
• Th
e pr
im ar
y se
rie s
w ith
A ct
H IB
, M en
H ib
rix , o
r P en
ta ce
l c on
si st
s of
3 d
os es
a nd
s ho
ul d
be a
dm in
is te
re d
at
2, 4
, a nd
6 m
on th
s of
a ge
. T he
p rim
ar y
se rie
s w
ith P
ed va
xH ib
o r C
O M
VA X
co ns
is ts
o f 2
d os
es a
nd s
ho ul
d be
a dm
in is
te re
d at
2 a
nd 4
m on
th s
of a
ge ; a
d os
e at
a ge
6 m
on th
s is
n ot
in di
ca te
d. •
O ne
b oo
st er
d os
e (d
os e
3 or
4 d
ep en
di ng
o n
va cc
in e
us ed
in p
rim ar
y se
rie s)
o f a
ny H
ib v
ac ci
ne s
ho ul
d be
a dm
in is
te re
d at
a ge
1 2
th ro
ug h
15 m
on th
s. A
n ex
ce pt
io n
is H
ib er
ix v
ac ci
ne . H
ib er
ix s
ho ul
d on
ly b
e
pr io
r d os
e of
H ib
-c on
ta in
in g
va cc
in e.
• Fo
r r ec
om m
en da
tio ns
o n
th e
us e
of M
en H
ib rix
in p
at ie
nt s
at in
cr ea
se d
ris k
fo r m
en in
go co
cc al
d is
ea se
, pl
ea se
re fe
r t o
th e
m en
in go
co cc
al v
ac ci
ne fo
ot no
te s
an d
al so
to M
M W
R Fe
br ua
ry 2
8, 2
01 4
/ 6 3(
RR 01
);1 -
13 , a
va ila
bl e
at h
tt p:
// w
w w
.c dc
.g ov
/m m
w r/
PD F/
rr /r
r6 30
1. pd
f.
3827_Ch19_447_496 02/07/15 12:05 PM Page 452
453
5. ty
pe b
(H ib
) c on
ju ga
te v
ac ci
ne (c
on t’d
) Ca
tc h-
up v
ac ci
na ti
on :
• w
ee ks
a ft
er d
os e
1, re
ga rd
le ss
o f H
ib v
ac ci
ne u
se d
in th
e pr
im ar
y se
rie s.
•
th e
se co
nd d
os e.
•
w hi
ch ev
er is
la te
r. • •
Fo r u
nv ac
ci na
te d
ch ild
re n
ag ed
1 5
m on
th s
or o
ld er
, a dm
in is
te r o
nl y
1 do
se .
• Fo
r o th
er c
at ch
-u p
gu id
an ce
, s ee
F ig
ur e
2. F
or c
at ch
-u p
gu id
an ce
re la
te d
to M
en H
ib rix
, p le
as e
se e
th e
m en
in go
co cc
al v
ac ci
ne fo
ot no
te s
an d
al so
M M
W R
Fe br
ua ry
2 8,
2 01
4 / 6
3( RR
01 );1
-1 3,
a va
ila bl
e at
ht
tp ://
w w
w .c
dc .g
ov /m
m w
r/ PD
F/ rr
/r r6
30 1.
pd f.
Va cc
in at
io n
of p
er so
ns w
it h
hi gh
-r is
k co
nd it
io ns
: •
C hi
ld re
n ag
ed 1
2 th
ro ug
h 59
m on
th s
w ho
a re
a t i
nc re
as ed
ri sk
fo r H
ib d
is ea
se , i
nc lu
di ng
c he
m ot
he ra
py
re ci
pi en
ts a
nd th
os e
w ith
a na
to m
ic o
r f un
ct io
na l a
sp le
ni a
(in cl
ud in
g si
ck le
c el
l d is
ea se
), hu
m an
sh ou
ld re
ce iv
e 2
ad di
tio na
l d os
es o
f H ib
v ac
ci ne
8 w
ee ks
a pa
rt ; c
hi ld
re n
w ho
re ce
iv ed
2 o
r m or
e d
os es
o f
H ib
v ac
ci ne
b ef
or e
12 m
on th
s of
a ge
s ho
ul d
re ce
iv e
1 ad
di tio
na l d
os e.
• Fo
r p at
ie nt
s yo
un ge
r t ha
n 5
ye ar
s of
a ge
u nd
er go
in g
ch em
ot he
ra py
o r r
ad ia
tio n
tr ea
tm en
t w ho
re ce
iv ed
a
H ib
v ac
ci ne
d os
e( s)
w ith
in 1
4 da
ys o
f s ta
rt in
g th
er ap
y or
d ur
in g
th er
ap y,
re pe
at th
e do
se (s
) a t l
ea st
3
m on
th s
fo llo
w in
g th
er ap
y co
m pl
et io
n. •
Re ci
pi en
ts o
f h em
at op
oi et
ic s
te m
c el
l t ra
ns pl
an t (
H SC
T) s
ho ul
d be
re va
cc in
at ed
w ith
a 3
-d os
e re
gi m
en
of H
ib v
ac ci
ne s
ta rt
in g
6 to
1 2
m on
th s
af te
r s uc
ce ss
fu l t
ra ns
pl an
t, re
ga rd
le ss
o f v
ac ci
na tio
n hi
st or
y; d
os es
sh
ou ld
b e
ad m
in is
te re
d at
le as
t 4 w
ee ks
a pa
rt .
• A
s in
gl e
do se
o f a
ny H
ib -c
on ta
in in
g va
cc in
e sh
ou ld
b e
ad m
in is
te re
d to
u ni
m m
un iz
ed *
ch ild
re n
an d
ad ol
es ce
nt s
15 m
on th
s of
a ge
a nd
o ld
er u
nd er
go in
g an
e le
ct iv
e sp
le ne
ct om
y; if
p os
si bl
e, v
ac ci
ne s
ho ul
d be
a dm
in is
te re
d at
le as
t 1 4
da ys
b ef
or e
pr oc
ed ur
e. •
H ib
v ac
ci ne
is n
ot ro
ut in
el y
re co
m m
en de
d fo
r p at
ie nt
s 5
ye ar
s or
o ld
er . H
ow ev
er , 1
d os
e of
H ib
v ac
ci ne
sh
ou ld
b e
ad m
in is
te re
d to
u ni
m m
un iz
ed *
pe rs
on s
ag ed
5 y
ea rs
o r o
ld er
w ho
h av
e an
at om
ic o
r fu
nc tio
na l a
sp le
ni a
(in cl
ud in
g si
ck le
c el
l d is
ea se
) a nd
u nv
ac ci
na te
d pe
rs on
s 5
th ro
ug h
18 y
ea rs
o f a
ge
* Pa
tie nt
s w ho
h av
e no
t r ec
ei ve
d a
pr im
ar y
se rie
s a nd
b oo
st er
d os
e or
a t l
ea st
1 d
os e
of H
ib v
ac ci
ne a
ft er
1 4
m on
th s o
f a ge
a re
c on
si de
re d
un im
m un
iz ed
. 6.
Pn eu
m oc
oc ca
l v ac
ci ne
s. (M
in im
um a
ge : 6
w ee
ks fo
r P C
V 13
, 2 y
ea rs
fo r P
PS V
23 )
Ro ut
in e
va cc
in at
io n
w it
h PC
V 13
: •
A dm
in is
te r a
4 -d
os e
se rie
s of
P C
V1 3
va cc
in e
at a
ge s
2, 4
, a nd
6 m
on th
s an
d at
a ge
1 2
th ro
ug h
15 m
on th
s. •
Fo r c
hi ld
re n
ag ed
1 4
th ro
ug h
59 m
on th
s w
ho h
av e
re ce
iv ed
a n
ag e-
ap pr
op ria
te s
er ie
s of
7 -v
al en
t P C
V (P
C V7
), ad
m in
is te
r a s
in gl
e su
pp le
m en
ta l d
os e
of 1
3- va
le nt
P C
V (P
C V1
3) .
Ca tc
h- up
v ac
ci na
ti on
w it
h PC
V 13
: •
A dm
in is
te r 1
d os
e of
P C
V1 3
to a
ll he
al th
y ch
ild re
n ag
ed 2
4 th
ro ug
h 59
m on
th s
w ho
a re
n ot
c om
pl et
el y
va cc
in at
ed fo
r t he
ir ag
e. •
Fo r o
th er
c at
ch -u
p gu
id an
ce , s
ee F
ig ur
e 2.
Va
cc in
at io
n of
p er
so ns
w it
h hi
gh -r
is k
co nd
it io
ns w
it h
PC V
13 a
nd P
PS V
23 :
• A
ll re
co m
m en
de d
PC V1
3 do
se s
sh ou
ld b
e ad
m in
is te
re d
pr io
r t o
PP SV
23 v
ac ci
na tio
n if
po ss
ib le
. •
Fo r c
hi ld
re n
2 th
ro ug
h 5
ye ar
s of
a ge
w ith
a ny
o f t
he fo
llo w
in g
co nd
iti on
s: c
hr on
ic h
ea rt
d is
ea se
(p
ar tic
ul ar
ly c
ya no
tic c
on ge
ni ta
l h ea
rt d
is ea
se a
nd c
ar di
ac fa
ilu re
); ch
ro ni
c lu
ng d
is ea
se (i
nc lu
di ng
co ch
le ar
im pl
an t;
si ck
le c
el l d
is ea
se a
nd o
th er
h em
og lo
bi no
pa th
ie s;
a na
to m
ic o
r f un
ct io
na l a
sp le
ni a;
H
IV in
fe ct
io n;
c hr
on ic
re na
l f ai
lu re
; n ep
hr ot
ic s
yn dr
om e;
d is
ea se
s as
so ci
at ed
w ith
tr ea
tm en
t w ith
im
m un
os up
pr es
si ve
d ru
gs o
r r ad
ia tio
n th
er ap
y, in
cl ud
in g
m al
ig na
nt n
eo pl
as m
s, le
uk em
ia s,
ly m
ph om
as ,
1. A
dm in
is te
r 1
do se
o f P
C V1
3 if
an y
in co
m pl
et e
sc he
du le
o f 3
d os
es o
f P C
V (P
C V7
a nd
/o r
PC V1
3) w
er e
re ce
iv ed
p re
vi ou
sl y.
2. A
dm in
is te
r 2 d
os es
o f P
C V1
3 at
le as
t 8 w
ee ks
a pa
rt if
u nv
ac ci
na te
d or
a ny
in co
m pl
et e
sc he
du le
o f f
ew er
th
an 3
d os
es o
f P C
V (P
C V7
a nd
/o r P
C V1
3) w
er e
re ce
iv ed
p re
vi ou
sl y.
3. A
dm in
is te
r 1 s
up pl
em en
ta l d
os e
of P
C V1
3 if
4 do
se s
of P
C V7
o r o
th er
a ge
-a pp
ro pr
ia te
c om
pl et
e PC
V7
se rie
s w
as re
ce iv
ed p
re vi
ou sl
y. 4.
Th e
m in
im um
in te
rv al
b et
w ee
n do
se s
of P
C V
(P C
V7 o
r P C
V1 3)
is 8
w ee
ks .
5. Fo
r c hi
ld re
n w
ith n
o hi
st or
y of
P PS
V2 3
va cc
in at
io n,
a dm
in is
te r P
PS V2
3 at
le as
t 8 w
ee ks
a ft
er th
e m
os t
re ce
nt d
os e
of P
C V1
3.
6. Pn
eu m
oc oc
ca l v
ac ci
ne s
(c on
t’d )
• di
se as
e an
d ot
he r h
em og
lo bi
no pa
th ie
s; a
na to
m ic
o r f
un ct
io na
l a sp
le ni
a; c
on ge
ni ta
l o r a
cq ui
re d
w ith
tr ea
tm en
t w ith
im m
un os
up pr
es si
ve d
ru gs
o r r
ad ia
tio n
th er
ap y,
in cl
ud in
g m
al ig
na nt
n eo
pl as
m s,
le
uk em
ia s,
ly m
ph om
as , a
nd H
od gk
in ’s
di se
as e;
g en
er al
iz ed
m al
ig na
nc y;
s ol
id o
rg an
tr an
sp la
nt at
io n;
o r
m ul
tip le
m ye
lo m
a: 1.
If ne
ith er
P C
V1 3
no r P
PS V2
3 ha
s be
en re
ce iv
ed p
re vi
ou sl
y, a
dm in
is te
r 1 d
os e
of P
C V1
3 no
w a
nd 1
d os
e of
P PS
V2 3
at le
as t 8
w ee
ks la
te r.
2. If
PC V1
3 ha
s b ee
n re
ce iv
ed p
re vi
ou sl
y bu
t P PS
V2 3
ha s n
ot , a
dm in
is te
r 1 d
os e
of P
PS V2
3 at
le as
t 8 w
ee ks
af
te r t
he m
os t r
ec en
t d os
e of
P C
V1 3.
3. If
PP SV
23 h
as b
ee n
re ce
iv ed
b ut
P C
V1 3
ha s
no t,
ad m
in is
te r 1
d os
e of
P C
V1 3
at le
as t 8
w ee
ks a
ft er
th e
m os
t r ec
en t d
os e
of P
PS V2
3. •
Fo r c
hi ld
re n
ag ed
6 th
ro ug
h 18
y ea
rs w
ith c
hr on
ic h
ea rt
d is
ea se
(p ar
tic ul
ar ly
c ya
no tic
c on
ge ni
ta l h
ea rt
di
se as
e an
d ca
rd ia
c fa
ilu re
), ch
ro ni
c lu
ng d
is ea
se (i
nc lu
di ng
a st
hm a
if tr
ea te
d w
ith h
ig h-
do se
o ra
l co
rt ic
os te
ro id
th er
ap y)
, d ia
be te
s m
el lit
us , a
lc oh
ol is
m , o
r c hr
on ic
li ve
r d is
ea se
, w ho
h av
e no
t r ec
ei ve
d PP
SV 23
, a dm
in is
te r 1
d os
e of
P PS
V2 3.
If P
C V1
3 ha
s be
en re
ce iv
ed p
re vi
ou sl
y, th
en P
PS V2
3 sh
ou ld
b e
ad m
in is
te re
d at
le as
t 8 w
ee ks
a ft
er a
ny p
rio r P
C V1
3 do
se .
• si
ck le
c el
l d is
ea se
o r o
th er
h em
og lo
bi no
pa th
ie s;
a na
to m
ic o
r f un
ct io
na l a
sp le
ni a;
c on
ge ni
ta l o
r a cq
ui re
d
w ith
tr ea
tm en
t w ith
im m
un os
up pr
es si
ve d
ru gs
o r r
ad ia
tio n
th er
ap y,
in cl
ud in
g m
al ig
na nt
n eo
pl as
m s,
le
uk em
ia s,
ly m
ph om
as , a
nd H
od gk
in ’s
di se
as e;
g en
er al
iz ed
m al
ig na
nc y;
s ol
id o
rg an
tr an
sp la
nt at
io n;
o r
m ul
tip le
m ye
lo m
a. 7.
In ac
ti va
te d
po lio
vi ru
s va
cc in
e (IP
V ).
(M in
im um
a ge
: 6 w
ee ks
) Ro
ut in
e va
cc in
at io
n: •
se rie
s s ho
ul d
be a
dm in
ist er
ed o
n or
a fte
r t he
fo ur
th b
irt hd
ay a
nd a
t l ea
st 6
m on
th s a
fte r t
he p
re vi
ou s d
os e.
Ca tc
h- up
v ac
ci na
ti on
: •
of im
m in
en t e
xp os
ur e
to c
irc ul
at in
g po
lio vi
ru s (
i.e ., t
ra ve
l t o
a po
lio -e
nd em
ic re
gi on
o r d
ur in
g an
o ut
br ea
k) .
• If
4 or
m or
e do
se s a
re a
dm in
is te
re d
be fo
re a
ge 4
y ea
rs , a
n ad
di tio
na l d
os e
sh ou
ld b
e ad
m in
is te
re d
at a
ge 4
th
ro ug
h 6
ye ar
s a nd
a t l
ea st
6 m
on th
s a fte
r t he
p re
vi ou
s d os
e. •
A fo
ur th
d os
e is
n ot
n ec
es sa
ry if
th e
th ird
d os
e w
as a
dm in
is te
re d
at a
ge 4
y ea
rs o
r o ld
er a
nd a
t l ea
st 6
m on
th s
af te
r t he
p re
vi ou
s d os
e. •
If bo
th O
PV a
nd IP
V w
er e
ad m
in is
te re
d as
p ar
t o f a
se rie
s, a
to ta
l o f 4
d os
es sh
ou ld
b e
ad m
in is
te re
d, re
ga rd
le ss
of
th e
ch ild
’s cu
rr en
t a ge
. I PV
is n
ot ro
ut in
el y
re co
m m
en de
d fo
r U .S
. r es
id en
ts a
ge d
18 y
ea rs
o r o
ld er
. •
Fo r o
th er
c at
ch -u
p gu
id an
ce , s
ee F
ig ur
e 2.
8. In
flu en
za v
ac ci
ne s.
(M in
im um
a ge
: 6 m
on th
s fo
r i na
ct iv
at ed
in flu
en za
v ac
ci ne
[I IV
], 2
ye ar
s fo
r l iv
e, a
tt en
ua te
d in
flu en
za v
ac ci
ne [L
A IV
])
Ro ut
in e
va cc
in at
io n:
• no
np re
gn an
t p er
so ns
a ge
d 2
th ro
ug h
49 y
ea rs
, e ith
er L
A IV
o r I
IV m
ay b
e us
ed . H
ow ev
er , L
A IV
s ho
ul d
N O
T be
a dm
in is
te re
d to
s om
e pe
rs on
s, in
cl ud
in g
1) p
er so
ns w
ho h
av e
ex pe
rie nc
ed s
ev er
e al
le rg
ic re
ac tio
ns
17 y
ea rs
re ce
iv in
g as
pi rin
o r a
sp iri
n- co
nt ai
ni ng
p ro
du ct
s; 3
) p er
so ns
w ho
a re
a lle
rg ic
to e
gg s;
4 ) p
re gn
an t
w om
en ; 5
) i m
m un
os up
pr es
se d
pe rs
on s;
6 ) c
hi ld
re n
2 th
ro ug
h 4
ye ar
s of
a ge
w ith
a st
hm a
or w
ho h
ad
pr ev
io us
4 8
ho ur
s. F
or a
ll ot
he r c
on tr
ai nd
ic at
io ns
a nd
p re
ca ut
io ns
to u
se o
f L A
IV , s
ee M
M W
R A
ug us
t 1 5,
20
14 /
63 (3
2) ;6
91 -6
97 [4
0 pa
ge s]
a va
ila bl
e at
ht
tp ://
w w
w .c
dc .g
ov /m
m w
r/ pd
f/ w
k/ m
m 63
32 .p
df .
Fo r c
hi ld
re n
ag ed
6 m
on th
s th
ro ug
h 8
ye ar
s: •
Fo r t
he 2
01 4-
15 s
ea so
n, a
dm in
is te
r 2 d
os es
(s ep
ar at
ed b
y at
le as
t 4 w
ee ks
) t o
ch ild
re n
w ho
a re
re ce
iv in
g
va cc
in e
re co
m m
en da
tio ns
, M M
W R
A ug
us t 1
5, 2
01 4
/ 6 3(
32 );6
91 -6
97 [4
0 pa
ge s]
a va
ila bl
e at
h tt
p: //
w w
w .
cd c.
go v/
m m
w r/
pd f/
w k/
m m
63 32
.p df
. • Fo
r p er
so n
s ag
ed 9
y ea
rs a
n d
o ld
er :
• A
dm in
is te
r 1 d
os e.
Fo r f
ur th
er g
ui da
nc e
on th
e us
e of
th e
va cc
in es
m en
tio ne
d be
lo w
, s ee
: h tt
p: //
w w
w .c
dc .g
ov /v
ac ci
ne s/
hc p/
ac ip
-r ec
s/ in
de x.
ht m
l.
3827_Ch19_447_496 02/07/15 12:05 PM Page 453
454
Fo r f
ur th
er g
ui da
nc e
on th
e us
e of
th e
va cc
in es
m en
tio ne
d be
lo w
, s ee
: h tt
p: //
w w
w .c
dc .g
ov /v
ac ci
ne s/
hc p/
ac ip
-r ec
s/ in
de x.
ht m
l. 9.
M
ea sl
es , m
um ps
, a nd
ru be
lla (M
M R)
v ac
ci ne
. ( M
in im
um a
ge : 1
2 m
on th
s fo
r r ou
ti ne
va
cc in
at io
n) Ro
ut in
e va
cc in
at io
n: •
A dm
in is
te r a
2 -d
os e
se rie
s of
M M
R va
cc in
e at
a ge
s 12
th ro
ug h
15 m
on th
s an
d 4
th ro
ug h
6 ye
ar s.
Th e
do se
. •
A dm
in is
te r 1
d os
e of
M M
R va
cc in
e to
in fa
nt s
ag ed
6 th
ro ug
h 11
m on
th s
be fo
re d
ep ar
tu re
fr om
th e
U ni
te d
at a
ge 1
2 th
ro ug
h 15
m on
th s
(1 2
m on
th s
if th
e ch
ild re
m ai
ns in
a n
ar ea
w he
re d
is ea
se ri
sk is
h ig
h) , a
nd th
e se
co nd
d os
e at
le as
t 4 w
ee ks
la te
r. •
A dm
in is
te r 2
d os
es o
f M M
R va
cc in
e to
c hi
ld re
n ag
ed 1
2 m
on th
s an
d ol
de r b
ef or
e de
pa rt
ur e
fr om
th e
th e
se co
nd d
os e
at le
as t 4
w ee
ks la
te r.
Ca tc
h- up
v ac
ci na
ti on
: •
En su
re th
at a
ll sc
ho ol
-a ge
d ch
ild re
n an
d ad
ol es
ce nt
s ha
ve h
ad 2
d os
es o
f M M
R va
cc in
e; th
e m
in im
um
in te
rv al
b et
w ee
n th
e 2
do se
s is
4 w
ee ks
. 10
. Va
ri ce
lla (V
A R)
v ac
ci ne
. ( M
in im
um a
ge : 1
2 m
on th
s)
Ro ut
in e
va cc
in at
io n:
• A
dm in
is te
r a 2
-d os
e se
rie s
of V
A R
va cc
in e
at a
ge s
12 th
ro ug
h 15
m on
th s
an d
4 th
ro ug
h 6
ye ar
s. T
he
se co
nd d
os e
m ay
b e
ad m
in is
te re
d be
fo re
a ge
4 y
ea rs
, p ro
vi de
d at
le as
t 3 m
on th
s ha
ve e
la ps
ed s
in ce
th e
va lid
. Ca
tc h-
up v
ac ci
na ti
on :
• En
su re
th at
a ll
pe rs
on s
ag ed
7 th
ro ug
h 18
y ea
rs w
ith ou
t e vi
de nc
e of
im m
un ity
(s ee
M M
W R
20 07
/ 56
[N o.
RR
-4 ],
av ai
la bl
e at
h tt
p: //
w w
w .c
dc .g
ov /m
m w
r/ pd
f/ rr
/r r5
60 4.
pd f )
h av
e 2
do se
s of
v ar
ic el
la v
ac ci
ne .
Fo r
ch ild
re n
ag ed
7 th
ro ug
h 12
y ea
rs , t
he re
co m
m en
de d
m in
im um
in te
rv al
b et
w ee
n do
se s
is 3
m on
th s
(if
pe rs
on s
ag ed
1 3
ye ar
s an
d ol
de r,
th e
m in
im um
in te
rv al
b et
w ee
n do
se s
is 4
w ee
ks .
11 .
H ep
at it
is A
(H ep
A ) v
ac ci
ne . (
M in
im um
a ge
: 1 2
m on
th s)
Ro ut
in e
va cc
in at
io n:
• In
iti at
e th
e 2-
do se
H ep
A v
ac ci
ne s
er ie
s at
1 2
th ro
ug h
23 m
on th
s; s
ep ar
at e
th e
2 do
se s
by 6
to 1
8 m
on th
s. •
C hi
ld re
n w
ho h
av e
re ce
iv ed
1 d
os e
of H
ep A
v ac
ci ne
b ef
or e
ag e
24 m
on th
s sh
ou ld
re ce
iv e
a se
co nd
d os
e
• Fo
r a ny
p er
so n
ag ed
2 y
ea rs
a nd
o ld
er w
ho h
as n
ot a
lre ad
y re
ce iv
ed th
e H
ep A
v ac
ci ne
s er
ie s,
2 d
os es
o f
H ep
A v
ac ci
ne s
ep ar
at ed
b y
6 to
1 8
m on
th s
m ay
b e
ad m
in is
te re
d if
im m
un ity
a ga
in st
h ep
at iti
s A
v iru
s in
fe ct
io n
is d
es ire
d.
Ca tc
h- up
v ac
ci na
ti on
: •
Th e
m in
im um
in te
rv al
b et
w ee
n th
e tw
o do
se s
is 6
m on
th s.
Sp
ec ia
l p op
ul at
io ns
: •
A dm
in is
te r 2
d os
es o
f H ep
A v
ac ci
ne a
t l ea
st 6
m on
th s
ap ar
t t o
pr ev
io us
ly u
nv ac
ci na
te d
pe rs
on s
w ho
liv
e in
a re
as w
he re
v ac
ci na
tio n
pr og
ra m
s ta
rg et
o ld
er c
hi ld
re n,
o r w
ho a
re a
t i nc
re as
ed ri
sk fo
r i nf
ec tio
n.
Th is
in cl
ud es
p er
so ns
tr av
el in
g to
o r w
or ki
ng in
c ou
nt rie
s th
at h
av e
hi gh
o r i
nt er
m ed
ia te
e nd
em ic
ity o
f in
fe ct
io n;
m en
h av
in g
se x
w ith
m en
; u se
rs o
f i nj
ec tio
n an
d no
n- in
je ct
io n
ill ic
it dr
ug s;
p er
so ns
w ho
w or
k w
ith H
AV -in
fe ct
ed p
rim at
es o
r w ith
H AV
in a
re se
ar ch
la bo
ra to
ry ; p
er so
ns w
ith c
lo tt
in g-
fa ct
or d
is or
de rs
; pe
rs on
s w
ith c
hr on
ic li
ve r d
is ea
se ; a
nd p
er so
ns w
ho a
nt ic
ip at
e cl
os e
pe rs
on al
c on
ta ct
(e .g
., ho
us eh
ol d
so on
a s
th e
ad op
tio n
is p
la nn
ed , i
de al
ly 2
o r m
or e
w ee
ks b
ef or
e th
e ar
riv al
o f t
he a
do pt
ee .
12 .
H um
an p
ap ill
om av
ir us
(H PV
) v ac
ci ne
s. (
M in
im um
a ge
: 9
ye ar
s fo
r H PV
2 [C
er va
ri x]
an
d H
PV 4
[G ar
da si
l])
Ro ut
in e
va cc
in at
io n:
• A
dm in
is te
r a 3
-d os
e se
rie s
of H
PV v
ac ci
ne o
n a
sc he
du le
o f 0
, 1 -2
, a nd
6 m
on th
s to
a ll
ad ol
es ce
nt s
ag ed
1 1
th ro
ug h
12 y
ea rs
. E ith
er H
PV 4
or H
PV 2
m ay
b e
us ed
fo r f
em al
es , a
nd o
nl y
H PV
4 m
ay b
e us
ed fo
r m al
es .
• Th
e va
cc in
e se
rie s
m ay
b e
st ar
te d
at a
ge 9
y ea
rs .
• Ca tc
h- up
v ac
ci na
ti on
: •
A dm
in is
te r t
he v
ac ci
ne s
er ie
s to
fe m
al es
(e ith
er H
PV 2
or H
PV 4)
a nd
m al
es (H
PV 4)
a t a
ge 1
3 th
ro ug
h 18
ye
ar s
if no
t p re
vi ou
sl y
va cc
in at
ed .
• U
se re
co m
m en
de d
ro ut
in e
do si
ng in
te rv
al s
(s ee
R ou
tin e
va cc
in at
io n
ab ov
e) fo
r v ac
ci ne
s er
ie s
ca tc
h- up
.
13 .
M en
in go
co cc
al c
on ju
ga te
v ac
ci ne
s. (M
in im
um a
ge : 6
w ee
ks fo
r H ib
-M en
C Y
[M en
H ib
ri x]
, 9 m
on th
s fo
r M en
A C
W Y-
D [M
en ac
tr a]
, 2 m
on th
s fo
r M en
A C
W Y-
C RM
[M
en ve
o] )
Ro ut
in e
va cc
in at
io n:
• A
dm in
is te
r a s
in gl
e do
se o
f M en
ac tr
a or
M en
ve o
va cc
in e
at a
ge 1
1 th
ro ug
h 12
y ea
rs , w
ith a
b oo
st er
d os
e at
a ge
1 6
ye ar
s. •
re ce
iv e
a 2-
do se
p rim
ar y
se rie
s of
M en
ac tr
a or
M en
ve o
w ith
a t l
ea st
8 w
ee ks
b et
w ee
n do
se s.
• Fo
r c hi
ld re
n ag
ed 2
m on
th s
th ro
ug h
18 y
ea rs
w ith
h ig
h- ris
k co
nd iti
on s,
s ee
b el
ow .
Ca tc
h- up
v ac
ci na
ti on
: •
A dm
in is
te r M
en ac
tr a
or M
en ve
o va
cc in
e at
a ge
1 3
th ro
ug h
18 y
ea rs
if n
ot p
re vi
ou sl
y va
cc in
at ed
. •
16 th
ro ug
h 18
y ea
rs w
ith a
m in
im um
in te
rv al
o f a
t l ea
st 8
w ee
ks b
et w
ee n
do se
s. • •
Fo r o
th er
c at
ch -u
p gu
id an
ce , s
ee F
ig ur
e 2.
Va cc
in at
io n
of p
er so
ns w
it h
hi gh
-r is
k co
nd it
io ns
a nd
o th
er p
er so
ns a
t i nc
re as
ed ri
sk o
f d is
ea se
: •
C hi
ld re
n w
ith a
na to
m ic
o r f
un ct
io na
l a sp
le ni
a (in
cl ud
in g
si ck
le c
el l d
is ea
se ):
1. M
en ve
o
o Ch
ild re
n w
ho in
iti at
e v ac
ci na
tio n
at 8
w ee
ks th
ro ug
h 6
m on
th s:
A dm
in is
te r d
os es
a t 2
, 4 , 6
, a nd
1 2
m on
th s
of a
ge .
o U
nv ac
ci na
te d
ch ild
re n
7 th
ro ug
h 23
m on
th s:
A dm
in is
te r 2
d os
es , w
ith th
e se
co nd
d os
e at
le as
t 1 2
w ee
ks
o Ch
ild re
n 24
m on
th s
an d
ol de
r w ho
h av
e no
t r ec
ei ve
d a
co m
pl et
e se
rie s:
A dm
in is
te r 2
p rim
ar y
do se
s at
le
as t 8
w ee
ks a
pa rt
. 2.
M en
H ib
rix o
Ch ild
re n
6 w
ee ks
th ro
ug h
18 m
on th
s: A
dm in
is te
r d os
es a
t 2 , 4
, 6 , a
nd 1
2 th
ro ug
h 15
m on
th s
of a
ge .
o at
le as
t 8 w
ee ks
a pa
rt to
e ns
ur e
pr ot
ec tio
n ag
ai ns
t s er
og ro
up s
C a
nd Y
m en
in go
co cc
al d
is ea
se .
3. M
en ac
tr a
o Ch
ild re
n 24
m on
th s a
nd o
ld er
w ho
h av
e no
t r ec
ei ve
d a
co m
pl et
e se
rie s:
A dm
in is
te r 2
p rim
ar y
do se
s at
le
as t 8
w ee
ks a
pa rt
. I f M
en ac
tr a
is a
dm in
is te
re d
to a
c hi
ld w
ith a
sp le
ni a
(in cl
ud in
g si
ck le
c el
l d is
ea se
), do
n ot
a dm
in is
te r M
en ac
tr a
un til
2 y
ea rs
o f a
ge a
nd a
t l ea
st 4
w ee
ks a
ft er
th e
co m
pl et
io n
of a
ll PC
V1 3
do se
s. •
1. M
en ve
o o
Ch ild
re n
w ho
in iti
at e v
ac ci
na tio
n at
8 w
ee ks
th ro
ug h
6 m
on th
s: A
dm in
is te
r d os
es a
t 2 , 4
, 6 , a
nd 1
2 m
on th
s of
a ge
. o
U nv
ac ci
na te
d ch
ild re
n 7
th ro
ug h
23 m
on th
s: A
dm in
is te
r 2 d
os es
, w ith
th e
se co
nd d
os e
at le
as t 1
2 w
ee ks
o Ch
ild re
n 24
m on
th s a
nd o
ld er
w ho
h av
e no
t r ec
ei ve
d a
co m
pl et
e se
rie s:
A dm
in is
te r 2
p rim
ar y
do se
s at
le
as t 8
w ee
ks a
pa rt
. 2.
M en
H ib
rix o
Ch ild
re n
6 w
ee ks
th ro
ug h
18 m
on th
s: A
dm in
is te
r d os
es a
t 2 , 4
, 6 , a
nd 1
2 th
ro ug
h 15
m on
th s
of a
ge .
o at
le as
t 8 w
ee ks
a pa
rt to
e ns
ur e
pr ot
ec tio
n ag
ai ns
t s er
og ro
up s
C a
nd Y
m en
in go
co cc
al d
is ea
se .
3. M
en ac
tr a
o Ch
ild re
n 9
th ro
ug h
23 m
on th
s: A
dm in
is te
r 2 p
rim ar
y do
se s
at le
as t 1
2 w
ee ks
a pa
rt .
o Ch
ild re
n 24
m on
th s
an d
ol de
r w ho
h av
e no
t r ec
ei ve
d a
co m
pl et
e se
rie s:
A dm
in is
te r 2
p rim
ar y
do se
s at
le
as t 8
w ee
ks a
pa rt
. •
Fo r c
hi ld
re n
w ho
tr av
el to
o r r
es id
e in
c ou
nt rie
s in
w hi
ch m
en in
go co
cc al
d is
ea se
is h
yp er
en de
m ic
o r
ep id
em ic
, i nc
lu di
ng c
ou nt
rie s
in th
e A
fr ic
an m
en in
gi tis
b el
t o r t
he H
aj j,
ad m
in is
te r a
n ag
e- ap
pr op
ria te
fo
rm ul
at io
n an
d se
rie s
of M
en ac
tr a
or M
en ve
o fo
r p ro
te ct
io n
ag ai
ns t s
er og
ro up
s A
a nd
W m
en in
go co
cc al
be ca
us e
it do
es n
ot c
on ta
in s
er og
ro up
s A
o r W
. •
Fo r c
hi ld
re n
at ri
sk d
ur in
g a
co m
m un
ity o
ut br
ea k
at tr
ib ut
ab le
to a
v ac
ci ne
s er
og ro
up , a
dm in
is te
r o r
co m
pl et
e an
a ge
- a nd
fo rm
ul at
io n-
ap pr
op ria
te s
er ie
s of
M en
H ib
rix , M
en ac
tr a,
o r M
en ve
o. •
Fo r b
oo st
er d
os es
a m
on g
pe rs
on s
w ith
h ig
h- ris
k co
nd iti
on s,
re fe
r t o
M M
W R
20 13
/ 62
(R R0
2) ;1
-2 2,
av
ai la
bl e
at h
tt p:
// w
w w
.c dc
.g ov
/m m
w r/
pr ev
ie w
/m m
w rh
tm l/r
r6 20
2a 1.
ht m
.
Fo r o
th er
c at
ch -u
p re
co m
m en
da tio
ns fo
r t he
se p
er so
ns , a
nd c
om pl
et e
in fo
rm at
io n
on u
se o
f m
en in
go co
cc al
v ac
ci ne
s, in
cl ud
in g
gu id
an ce
re la
te d
to v
ac ci
na tio
n of
p er
so ns
a t i
nc re
as ed
ri sk
o f i
nf ec
tio n,
se
e M
M W
R M
ar ch
2 2,
2 01
3 / 6
2( RR
02 );1
-2 2,
a va
ila bl
e at
h tt
p: //
w w
w .c
dc .g
ov /m
m w
r/ pd
f/ rr
/r r6
20 2.
pd f.
C S
24 40
83 -B
Ta b
le 1
9– 1 !
R ec
o m
m en
d ed
Im m
u n
iz at
io n
S ch
ed u
le fo
r P
er so
n s
A g
ed 0
T h
ro u
g h
18 Y
ea rs
— U
n it
ed S
ta te
s, 2
01 5—
co n
t’ d
3827_Ch19_447_496 02/07/15 12:05 PM Page 454
455 Ta
b le
1 9–
2 !
C at
ch -U
p Im
m u
n iz
at io
n S
ch ed
u le
fo r
P er
so n
s A
g ed
4 M
o n
th s
Th ro
u g
h 1
8 Y
ea rs
W h
o S
ta rt
L at
e o
r W
h o
A re
M o
re
Th an
1 M
o n
th B
eh in
d –
U n
it ed
S ta
te s,
2 01
5
FI G
U RE
2 . C
at ch
-u p
im m
un iz
at io
n sc
he du
le fo
r p er
so ns
a ge
d 4
m on
th s
th ro
ug h
18 y
ea rs
w ho
s ta
rt la
te o
r w ho
a re
m or
e th
an 1
m on
th b
eh in
d —
U ni
te d
St at
es , 2
01 5.
ap pr
op ria
te fo
r t he
c hi
ld ’s
ag e.
A lw
ay s
us e
th is
ta bl
e in
c on
ju nc
tio n
w ith
F ig
ur e
1 an
d th
e fo
ot no
te s
th at
fo llo
w .
Ch ild
re n
ag e
4 m
on th
s th
ro ug
h 6
ye ar
s
Va cc
in e
M in
im um
A
ge fo
r D
os e
1
M in
im um
In te
rv al
B et
w ee
n D
os es
D os
e 1
to D
os e
2 D
os e
2 to
D os
e 3
D os
e 3
to D
os e
4 D
os e
4 to
D os
e 5
H ep
at iti
s B1
Bi rt
h 4
w ee
ks 8
w ee
ks
an d
.
Ro ta
vi ru
s2 6
w ee
ks 4
w ee
ks 4
w ee
ks 2
D ip
ht he
ria , t
et an
us , a
nd a
ce l-
lu la
r p er
tu ss
is 3
6 w
ee ks
4 w
ee ks
4 w
ee ks
6 m
on th
s 6
m on
th s3
ty
p e
b 5
6 w
ee ks
4 w
ee ks
st
b ir
th da
y.
N o
fu rt
he r d
os es
n ee
de d
m on
th s
or o
ld er
.
4 w
ee ks
5 if
cu rr
en t a
ge is
y ou
ng er
th an
1 2
m on
th s
an d
yo un
ge r t
ha n
ag e
7 m
on th
s, a
n d
a t l
ea st
1 p
re vi
ou s
do se
w as
P RP
-T (A
ct H
ib ,
Pe nt
ac el
) o r u
nk no
w n.
8 w
ee ks
an
d 5
• if
cu rr
en t a
ge is
y ou
ng er
th an
1 2
m on
th s
an
d
O R
• if
cu rr
en t a
ge is
1 2
th ro
ug h
59 m
on th
s
an d
st b
ir th
da y,
a n
d s
ec on
d do
se
ad m
in is
te re
d at
y ou
ng er
th an
1 5
m on
th s;
O
R •
if b
ot h
do se
s w
er e
PR P-
O M
P (P
ed va
xH IB
; C om
va x)
an
d w
er e
ad m
in is
te re
d b
ef or
e th
e 1s
t b ir
th da
y.
N o
fu rt
he r d
os es
n ee
de d
if pr
ev io
us d
os e
w as
a dm
in is
te re
d at
a ge
1 5
m on
th s
or o
ld er
.
Th is
d os
e on
ly n
ec es
sa ry
fo r c
hi ld
re n
ag e
12 th
ro ug
h 59
m on
th s
w ho
re ce
iv ed
3 d
os es
b ef
or e
th e
1s t b
ir th
da y.
Pn eu
m oc
oc ca
l6 6
w ee
ks
4 w
ee ks
st
b ir
th da
y.
st b
ir th
da y
or a
ft er
.
N o
fu rt
he r d
os es
n ee
de d
ol de
r.
4 w
ee ks
if
cu rr
en t a
ge is
y ou
ng er
th an
1 2
m on
th s
an d
pr ev
io us
d os
e gi
ve n
at <
7m on
th s
ol d.
if pr
ev io
us d
os e
gi ve
n be
tw ee
n 7-
11 m
on th
s (w
ai t u
nt il
at le
as t 1
2 m
on th
s ol
d) ;
O R
if cu
rr en
t a ge
is 1
2 m
on th
s or
o ld
er a
nd a
t l ea
st 1
d os
e w
as g
iv en
b ef
or e
ag e
12 m
on th
s.
N o
fu rt
he r d
os es
n ee
de d
fo r h
ea lth
y ch
ild re
n if
p re
vi ou
s do
se a
dm in
is te
re d
at
ag e
24 m
on th
s or
o ld
er .
Th is
d os
e on
ly n
ec es
sa ry
fo r c
hi ld
re n
ag ed
1 2
th ro
ug h
59 m
on th
s w
ho re
ce iv
ed 3
d os
es b
ef or
e ag
e 12
m on
th s
or fo
r c hi
ld re
n at
h ig
h ris
k w
ho re
ce iv
ed 3
d os
es a
t a ny
a ge
.
In ac
tiv at
ed p
ol io
vi ru
s7 6
w ee
ks 4
w ee
ks 7
4 w
ee ks
7 6
m on
th s7
M en
in go
co cc
al 13
6 w
ee ks
8 w
ee ks
13 Se
e fo
ot no
te 1
3 Se
e fo
ot no
te 1
3
M ea
sl es
, m um
p s,
ru b
el la
9 12
m on
th s
4 w
ee ks
Va ric
el la
10 12
m on
th s
3 m
on th
s
H ep
at iti
s A
11 12
m on
th s
6 m
on th
s
C h
ild re
n a
n d
a d
ol es
ce nt
s ag
e 7
th ro
ug h
1 8
ye ar
s
Te ta
nu s,
d ip
ht he
ria ; t
et an
us ,
di p
ht he
ria , a
nd a
ce llu
la r
p er
tu ss
is 4
7 ye
ar s4
4 w
ee ks
4 w
ee ks
st b
irt hd
ay .
st b
ir th
da y.
6 m
on th
s st
b ir
th da
y.
H um
an p
ap ill
om av
iru s1
2 9
ye ar
s Ro
ut in
e do
si ng
in te
rv al
s ar
e re
co m
m en
de d.
12
H ep
at iti
s A
11 N
ot
ap p
lic ab
le (N
/A )
6 m
on th
s
H ep
at iti
s B1
N /A
4 w
ee ks
8 w
ee ks
a n
d
In ac
tiv at
ed p
ol io
vi ru
s7 N
/A 4
w ee
ks 4
w ee
ks 7
6 m
on th
s7
M en
in go
co cc
al 13
N /A
8 w
ee ks
13
M ea
sl es
, m um
p s,
ru b
el la
9 N
/A 4
w ee
ks
Va ric
el la
10 N
/A 3
m on
th s
if yo
un ge
r t ha
n ag
e 13
y ea
rs .
4 w
ee ks
if a
ge 1
3 ye
ar s
or o
ld er
.
N O
TE : T
he a
bo ve
re co
m m
en da
ti on
s m
us t b
e re
ad a
lo ng
w it
h th
e fo
ot no
te s
of th
is s
ch ed
ul e.
3827_Ch19_447_496 02/07/15 12:05 PM Page 455
456 Ta
b le
1 9–
2 !
C at
ch -U
p Im
m u
n iz
at io
n S
ch ed
u le
fo r
P er
so n
s A
g ed
4 M
o n
th s
Th ro
u g
h 1
8 Y
ea rs
W h
o S
ta rt
L at
e o
r W
h o
A re
M o
re
Th an
1 M
o n
th B
eh in
d –
U n
it ed
S ta
te s,
2 01
5— co
n t’
d
Fo ot
no te
s —
R ec
om m
en de
d im
m un
iz at
io n
sc he
du le
fo r p
er so
ns a
ge d
0 th
ro ug
h 18
y ea
rs —
U ni
te d
St at
es , 2
01 5
Fo
r f ur
th er
g ui
da nc
e on
th e
us e
of th
e va
cc in
es m
en tio
ne d
be lo
w , s
ee : h
tt p:
// w
w w
.c dc
.g ov
/v ac
ci ne
s/ hc
p/ ac
ip -r
ec s/
in de
x. ht
m l.
Fo
r v ac
ci ne
re co
m m
en da
tio ns
fo r p
er so
ns 1
9 ye
ar s
of a
ge a
nd o
ld er
, s ee
th e
A du
lt Im
m un
iz at
io n
Sc he
du le
. A
d d
it io
na l i
nf or
m at
io n
• Fo
r c on
tr ai
nd ic
at io
ns a
nd p
re ca
ut io
ns to
u se
o f a
v ac
ci ne
a nd
fo r a
dd iti
on al
in fo
rm at
io n
re ga
rd in
g th
at v
ac ci
ne , v
ac ci
na tio
n pr
ov id
er s
sh ou
ld c
on su
lt th
e re
le va
nt A
C IP
s ta
te m
en t a
va ila
bl e
on lin
e at
ht
tp ://
w w
w .c
dc .g
ov /v
ac ci
ne s/
hc p/
ac ip
-r ec
s/ in
de x.
ht m
l. •
Fo r p
ur po
se s
of c
al cu
la tin
g in
t e rv
al s
be tw
ee n
do se
s, 4
w ee
ks =
2 8
da ys
. I nt
er va
ls o
f 4 m
on th
s or
g re
at er
a re
d et
er m
in ed
b y
ca le
nd ar
m on
th s.
• Va
cc in
e do
se s
ad m
in is
te re
d 4
da ys
o r l
es s
be fo
re th
e m
in im
um in
te rv
al a
re c
on si
de re
d va
lid . D
os es
o f a
ny v
ac ci
ne a
dm in
is te
re d
≥ 5
da ys
e ar
lie r t
ha n
th e
m in
im um
in te
rv al
o r m
in im
um a
ge s
ho ul
d no
t be
c ou
nt ed
a s
va lid
d os
es a
nd s
ho ul
d be
re pe
at ed
a s
ag e-
ap pr
op ria
te . T
he re
pe at
d os
e sh
ou ld
b e
sp ac
ed a
ft er
th e
in va
lid d
os e
by th
e re
co m
m en
de d
m in
im um
in te
rv al
. F or
fu rt
he r d
et ai
ls , s
ee M
M W
R,
G en
er al
R ec
om m
en da
tio ns
o n
Im m
un iz
at io
n an
d Re
po rt
s / V
ol . 6
0 / N
o. 2
; T ab
le 1
. R ec
om m
en de
d an
d m
in im
um a
ge s a
nd in
te rv
al s b
et w
ee n
va cc
in e
do se
s a va
ila bl
e on
lin e
at
ht tp
:// w
w w
.c dc
.g ov
/m m
w r/
pd f/
rr /r
r6 00
2. pd
f. •
In f o
rm at
io n
on tr
av el
v ac
ci ne
re qu
ire m
en ts
a nd
re co
m m
en da
tio ns
is a
va ila
bl e
at h
tt p:
// w
w w
nc .c
dc .g
ov /t
ra ve
l/d es
tin at
io ns
/li st
. •
in G
en er
al R
ec om
m en
da tio
ns o
n Im
m un
iz at
io n
(A C
IP ),
av ai
la bl
e at
h tt
p: //
w w
w .c
dc .g
ov /m
m w
r/ pd
f/ rr
/r r6
00 2.
pd f.;
a nd
A m
er ic
an A
ca de
m y
of P
ed ia
tr ic
s. “I
m m
un iz
at io
n in
S pe
ci al
C lin
ic al
C irc
um st
an ce
s,” in
P ic
ke rin
g LK
, B ak
er C
J, Ki
m be
rli n
D W
, L on
g SS
e ds
. R ed
B oo
k: 2
01 2
re po
rt o
f t he
C om
m itt
ee o
n In
fe ct
io us
D is
ea se
s. 29
th e
d. E
lk G
ro ve
V ill
ag e,
IL : A
m er
ic an
A ca
de m
y of
P ed
ia tr
ic s.
1.
H ep
at it
is B
(H ep
B) v
ac ci
ne . (
M in
im um
a ge
: b ir
th )
Ro ut
in e
va cc
in at
io n:
A
t b ir
th :
• A
dm in
is te
r m on
ov al
en t H
ep B
va cc
in e
to a
ll ne
w bo
rn s
be fo
re h
os pi
ta l d
is ch
ar ge
. •
Fo r i
nf an
ts b
or n
to h
ep at
iti s
B su
rf ac
e an
tig en
(H Bs
A g)
-p os
iti ve
m ot
he rs
, a dm
in is
te r H
ep B
va cc
in e
an d
0. 5
m L
of h
ep at
iti s
B im
m un
e gl
ob ul
in (H
BI G
) w ith
in 1
2 ho
ur s
of b
irt h.
T he
se in
fa nt
s sh
ou ld
b e
te st
ed
fo r H
Bs A
g an
d an
tib od
y to
H Bs
A g
(a nt
i-H Bs
) 1 to
2 m
on th
s af
te r c
om pl
et io
n of
th e
H ep
B se
rie s
at a
ge 9
th
ro ug
h 18
m on
th s
(p re
fe ra
bl y
at th
e ne
xt w
el l-c
hi ld
v is
it) .
• If
m ot
he r’s
H Bs
A g
st at
us is
u nk
no w
n, w
ith in
1 2
ho ur
s of
b irt
h ad
m in
is te
r H ep
B va
cc in
e re
ga rd
le ss
o f b
irt h
w ei
gh t.
Fo r i
nf an
ts w
ei gh
in g
le ss
th an
2 ,0
00 g
ra m
s, a
dm in
is te
r H BI
G in
a dd
iti on
to H
ep B
va cc
in e
w ith
in
12 h
ou rs
o f b
irt h.
D et
er m
in e
m ot
he r’s
H Bs
A g
st at
us a
s so
on a
s po
ss ib
le a
nd , i
f m ot
he r i
s H
Bs A
g- po
si tiv
e,
al so
a dm
in is
te r H
BI G
fo r i
nf an
ts w
ei gh
in g
2, 00
0 gr
am s
or m
or e
as s
oo n
as p
os si
bl e,
b ut
n o
la te
r t ha
n ag
e 7
da ys
. D
os es
fo llo
w in
g th
e bi
rt h
do se
: •
Th e
se co
nd d
os e
sh ou
ld b
e ad
m in
is te
re d
at a
ge 1
o r 2
m on
th s.
M on
ov al
en t H
ep B
va cc
in e
sh ou
ld b
e us
ed fo
r d os
es a
dm in
is te
re d
be fo
re a
ge 6
w ee
ks .
• In
fa nt
s w
ho d
id n
ot re
ce iv
e a
bi rt
h do
se s
ho ul
d re
ce iv
e 3
do se
s of
a H
ep B-
co nt
ai ni
ng v
ac ci
ne o
n a
sc he
du le
o f 0
, 1 to
2 m
on th
s, a
nd 6
m on
th s
st ar
tin g
as s
oo n
as fe
as ib
le . S
ee F
ig ur
e 2.
• th
e th
ird d
os e
at le
as t 8
w ee
ks a
ft er
th e
se co
nd d
os e
A N
D a
t l ea
st 1
6 w
ee ks
a ft
er th
e (t
hi rd
o r f
ou rt
h) d
os e
in th
e H
ep B
va cc
in e
se rie
s sh
ou ld
b e
ad m
in is
te re
d no
e ar
lie r t
ha n
ag e
24 w
ee ks
. •
A dm
in is
tr at
io n
of a
to ta
l o f 4
d os
es o
f H ep
B va
cc in
e is
p er
m itt
ed w
he n
a co
m bi
na tio
n va
cc in
e co
nt ai
ni ng
H
ep B
is a
dm in
is te
re d
af te
r t he
b irt
h do
se .
Ca tc
h- up
v ac
ci na
ti on
: •
U nv
ac ci
na te
d pe
rs on
s sh
ou ld
c om
pl et
e a
3- do
se s
er ie
s. •
A 2
-d os
e se
rie s
(d os
es s
ep ar
at ed
b y
at le
as t 4
m on
th s)
o f a
du lt
fo rm
ul at
io n
Re co
m bi
va x
H B
is li
ce ns
ed fo
r us
e in
c hi
ld re
n ag
ed 1
1 th
ro ug
h 15
y ea
rs .
• Fo
r o th
er c
at ch
-u p
gu id
an ce
, s ee
F ig
ur e
2. 2.
Ro
ta vi
ru s
(R V
) v ac
ci ne
s. (M
in im
um a
ge : 6
w ee
ks fo
r b ot
h RV
1 [R
ot ar
ix ] a
nd
RV 5
[R ot
aT eq
]) Ro
ut in
e va
cc in
at io
n: A
dm in
is te
r a s
er ie
s of
R V
va cc
in e
to a
ll in
fa nt
s as
fo llo
w s:
1.
I f R
ot ar
ix is
u se
d, a
dm in
is te
r a 2
-d os
e se
rie s
at 2
a nd
4 m
on th
s of
a ge
. 2.
I f R
ot aT
eq is
u se
d, a
dm in
is te
r a 3
-d os
e se
rie s
at a
ge s
2, 4
, a nd
6 m
on th
s.
3. I
f a ny
d os
e in
th e
se rie
s w
as R
ot aT
eq o
r v ac
ci ne
p ro
du ct
is u
nk no
w n
fo r a
ny d
os e
in th
e se
rie s,
a to
ta l o
f 3
do se
s of
R V
va cc
in e
sh ou
ld b
e ad
m in
is te
re d.
Ca
tc h-
up v
ac ci
na ti
on :
• fo
r i nf
an ts
a ge
d 15
w ee
ks , 0
d ay
s or
o ld
er .
• • Fo
r o th
er c
at ch
-u p
gu id
an ce
, s ee
F ig
ur e
2. 3.
D
ip ht
he ri
a an
d te
ta nu
s to
xo id
s an
d ac
el lu
la r p
er tu
ss is
(D Ta
P) v
ac ci
ne . (
M in
im um
ag
e: 6
w ee
ks . E
xc ep
ti on
: D Ta
P- IP
V [K
in ri
x] : 4
y ea
rs )
Ro ut
in e
va cc
in at
io n:
• A
dm in
is te
r a 5
-d os
e se
rie s
of D
Ta P
va cc
in e
at a
ge s
2, 4
, 6 , 1
5 th
ro ug
h 18
m on
th s,
a nd
4 th
ro ug
h 6
ye ar
s.
Th e
fo ur
th d
os e
m ay
b e
ad m
in is
te re
d as
e ar
ly a
s ag
e 12
m on
th s,
p ro
vi de
d at
le as
t 6 m
on th
s ha
ve e
la ps
ed
si nc
e th
e th
ird d
os e.
H ow
ev er
, t he
fo ur
th d
os e
of D
Ta P
ne ed
n ot
b e
re pe
at ed
if it
w as
a dm
in is
te re
d at
le
as t 4
m on
th s
af te
r t he
th ird
d os
e of
D Ta
P.
3.
D ip
ht he
ri a
an d
te ta
nu s
to xo
id s
an d
ac el
lu la
r p er
tu ss
is (D
Ta P)
v ac
ci ne
(c on
t’d )
Ca tc
h- up
v ac
ci na
ti on
: • •
Fo r o
th er
c at
ch -u
p gu
id an
ce , s
ee F
ig ur
e 2.
4.
Te ta
nu s
an d
di ph
th er
ia to
xo id
s an
d ac
el lu
la r p
er tu
ss is
(T da
p) v
ac ci
ne . (
M in
im um
ag
e: 1
0 ye
ar s
fo r b
ot h
Bo os
tr ix
a nd
A da
ce l)
Ro ut
in e
va cc
in at
io n:
•
A dm
in is
te r 1
d os
e of
T da
p va
cc in
e to
a ll
ad ol
es ce
nt s
ag ed
1 1
th ro
ug h
12 y
ea rs
. •
Td ap
m ay
b e
ad m
in is
te re
d re
ga rd
le ss
o f t
he in
te rv
al s
in ce
th e
la st
te ta
nu s
an d
di ph
th er
ia to
xo id
- co
nt ai
ni ng
v ac
ci ne
. •
A dm
in is
te r 1
d os
e of
T da
p va
cc in
e to
p re
gn an
t a do
le sc
en ts
d ur
in g
ea ch
p re
gn an
cy (p
re fe
rr ed
d ur
in g
27
th ro
ug h
36 w
ee ks
’ g es
ta tio
n) re
ga rd
le ss
o f t
im e
si nc
e pr
io r T
d or
T da
p va
cc in
at io
n.
Ca tc
h- up
v ac
ci na
ti on
: •
Pe rs
on s
ag ed
7 y
ea rs
a nd
o ld
er w
ho a
re n
ot fu
lly im
m un
iz ed
w ith
D Ta
P va
cc in
e sh
ou ld
re ce
iv e
Td ap
va cc
in e.
F or
c hi
ld re
n 7
th ro
ug h
10 y
ea rs
w ho
re ce
iv e
a do
se o
f T da
p as
p ar
t o f t
he c
at ch
-u p
se rie
s, a
n ad
ol es
ce nt
T da
p va
cc in
e do
se a
t a ge
1 1
th ro
ug h
12 y
ea rs
s ho
ul d
N O
T be
a dm
in is
te re
d. T
d sh
ou ld
b e
ad m
in is
te re
d in
st ea
d 10
y ea
rs a
ft er
th e
Td ap
d os
e. •
Pe rs
on s
ag ed
1 1
th ro
ug h
18 y
ea rs
w ho
h av
e no
t r ec
ei ve
d Td
ap v
ac ci
ne s
ho ul
d re
ce iv
e a
do se
fo llo
w ed
b y
te ta
nu s
an d
di ph
th er
ia to
xo id
(T d)
b oo
st er
d os
es e
ve ry
1 0
ye ar
s th
er ea
ft er
. •
In ad
ve rt
en t d
os es
o f D
Ta P
va cc
in e:
- If
ad m
in is
te re
d in
ad ve
rt en
tly to
a c
hi ld
a ge
d 7
th ro
ug h
10 y
ea rs
m ay
c ou
nt a
s pa
rt o
f t he
c at
ch -u
p
se rie
s. T
hi s
do se
m ay
c ou
nt a
s th
e ad
ol es
ce nt
T da
p do
se , o
r t he
c hi
ld c
an la
te r r
ec ei
ve a
T da
p bo
os te
r do
se a
t a ge
1 1
th ro
ug h
12 y
ea rs
. -
If ad
m in
is te
re d
in ad
ve rt
en tly
to a
n ad
ol es
ce nt
a ge
d 11
th ro
ug h
18 y
ea rs
, t he
d os
e sh
ou ld
b e
co un
te d
as th
e ad
ol es
ce nt
T da
p bo
os te
r. •
Fo r o
th er
c at
ch -u
p gu
id an
ce , s
ee F
ig ur
e 2.
5.
ty pe
b (H
ib ) c
on ju
ga te
v ac
ci ne
. (M
in im
um a
ge :
6 w
ee ks
fo
r P RP
-T [A
C TH
IB , D
Ta P-
IP V
/H ib
(P en
ta ce
l) an
d H
ib -M
en C
Y (M
en H
ib ri
x) ],
PR P-
O M
P [P
ed va
xH IB
o r C
O M
VA X
], 12
m on
th s
fo r P
RP -T
[H ib
er ix
])
Ro ut
in e
va cc
in at
io n:
• A
dm in
is te
r a 2
- o r 3
-d os
e H
ib v
ac ci
ne p
rim ar
y se
rie s
an d
a bo
os te
r d os
e (d
os e
3 or
4 d
ep en
di ng
o n
va cc
in e
us ed
in p
rim ar
y se
rie s)
a t a
ge 1
2 th
ro ug
h 15
m on
th s
to c
om pl
et e
a fu
ll H
ib v
ac ci
ne s
er ie
s. •
Th e
pr im
ar y
se rie
s w
ith A
ct H
IB , M
en H
ib rix
, o r P
en ta
ce l c
on si
st s
of 3
d os
es a
nd s
ho ul
d be
a dm
in is
te re
d at
2,
4 , a
nd 6
m on
th s
of a
ge . T
he p
rim ar
y se
rie s
w ith
P ed
va xH
ib o
r C O
M VA
X co
ns is
ts o
f 2 d
os es
a nd
s ho
ul d
be a
dm in
is te
re d
at 2
a nd
4 m
on th
s of
a ge
; a d
os e
at a
ge 6
m on
th s
is n
ot in
di ca
te d.
• O
ne b
oo st
er d
os e
(d os
e 3
or 4
d ep
en di
ng o
n va
cc in
e us
ed in
p rim
ar y
se rie
s) o
f a ny
H ib
v ac
ci ne
s ho
ul d
be a
dm in
is te
re d
at a
ge 1
2 th
ro ug
h 15
m on
th s.
A n
ex ce
pt io
n is
H ib
er ix
v ac
ci ne
. H ib
er ix
s ho
ul d
on ly
b e
pr io
r d os
e of
H ib
-c on
ta in
in g
va cc
in e.
• Fo
r r ec
om m
en da
tio ns
o n
th e
us e
of M
en H
ib rix
in p
at ie
nt s
at in
cr ea
se d
ris k
fo r m
en in
go co
cc al
d is
ea se
, pl
ea se
re fe
r t o
th e
m en
in go
co cc
al v
ac ci
ne fo
ot no
te s
an d
al so
to M
M W
R Fe
br ua
ry 2
8, 2
01 4
/ 6 3(
RR 01
);1 -
13 , a
va ila
bl e
at h
tt p:
// w
w w
.c dc
.g ov
/m m
w r/
PD F/
rr /r
r6 30
1. pd
f.
3827_Ch19_447_496 02/07/15 12:05 PM Page 456
457
5.
ty pe
b (H
ib ) c
on ju
ga te
v ac
ci ne
(c on
t’d )
Ca tc
h- up
v ac
ci na
ti on
: •
w ee
ks a
ft er
d os
e 1,
re ga
rd le
ss o
f H ib
v ac
ci ne
u se
d in
th e
pr im
ar y
se rie
s. •
th e
se co
nd d
os e.
•
w hi
ch ev
er is
la te
r. • •
Fo r u
nv ac
ci na
te d
ch ild
re n
ag ed
1 5
m on
th s
or o
ld er
, a dm
in is
te r o
nl y
1 do
se .
• Fo
r o th
er c
at ch
-u p
gu id
an ce
, s ee
F ig
ur e
2. F
or c
at ch
-u p
gu id
an ce
re la
te d
to M
en H
ib rix
, p le
as e
se e
th e
m en
in go
co cc
al v
ac ci
ne fo
ot no
te s
an d
al so
M M
W R
Fe br
ua ry
2 8,
2 01
4 / 6
3( RR
01 );1
-1 3,
a va
ila bl
e at
ht
tp ://
w w
w .c
dc .g
ov /m
m w
r/ PD
F/ rr
/r r6
30 1.
pd f.
Va c c
in at
io n
of p
er so
ns w
it h
hi gh
-r is
k co
nd it
io ns
: •
C hi
ld re
n ag
ed 1
2 th
ro ug
h 59
m on
th s
w ho
a re
a t i
nc re
as ed
ri sk
fo r H
ib d
is ea
se , i
nc lu
di ng
c he
m ot
he ra
py
re ci
pi en
ts a
nd th
os e
w ith
a na
to m
ic o
r f un
ct io
na l a
sp le
ni a
(in cl
ud in
g si
ck le
c el
l d is
ea se
), hu
m an
sh ou
ld re
ce iv
e 2
ad di
tio na
l d os
es o
f H ib
v ac
ci ne
8 w
ee ks
a pa
rt ; c
hi ld
re n
w ho
re ce
iv ed
2 o
r m or
e d
os es
o f
H ib
v ac
ci ne
b ef
or e
12 m
on th
s of
a ge
s ho
ul d
re ce
iv e
1 ad
di tio
na l d
os e.
• Fo
r p at
ie nt
s yo
un ge
r t ha
n 5
ye ar
s of
a ge
u nd
er go
in g
ch em
ot he
ra py
o r r
ad ia
tio n
tr ea
tm en
t w ho
re ce
iv ed
a
H ib
v ac
ci ne
d os
e( s)
w ith
in 1
4 da
ys o
f s ta
rt in
g th
er ap
y or
d ur
in g
th er
ap y,
re pe
at th
e do
se (s
) a t l
ea st
3
m on
th s
fo llo
w in
g th
er ap
y co
m pl
et io
n. •
Re ci
pi en
ts o
f h em
at op
oi et
ic s
te m
c el
l t ra
ns pl
an t (
H SC
T) s
ho ul
d be
re va
cc in
at ed
w ith
a 3
-d os
e re
gi m
en
of H
ib v
ac ci
ne s
ta rt
in g
6 to
1 2
m on
th s
af te
r s uc
ce ss
fu l t
ra ns
pl an
t, re
ga rd
le ss
o f v
ac ci
na tio
n hi
st or
y; d
os es
sh
ou ld
b e
ad m
in is
te re
d at
le as
t 4 w
ee ks
a pa
rt .
• A
s in
gl e
do se
o f a
ny H
ib -c
on ta
in in
g va
cc in
e sh
ou ld
b e
ad m
in is
te re
d to
u ni
m m
un iz
ed *
ch ild
re n
an d
ad ol
es ce
nt s
15 m
on th
s of
a ge
a nd
o ld
er u
nd er
go in
g an
e le
ct iv
e sp
le ne
ct om
y; if
p os
si bl
e, v
ac ci
ne s
ho ul
d be
a dm
in is
te re
d at
le as
t 1 4
da ys
b ef
or e
pr oc
ed ur
e. •
H ib
v ac
ci ne
is n
ot ro
ut in
el y
re co
m m
en de
d fo
r p at
ie nt
s 5
ye ar
s or
o ld
er . H
ow ev
er , 1
d os
e of
H ib
v ac
ci ne
sh
ou ld
b e
ad m
in is
te re
d to
u ni
m m
un iz
ed *
pe rs
on s
ag ed
5 y
ea rs
o r o
ld er
w ho
h av
e an
at om
ic o
r fu
nc tio
na l a
sp le
ni a
(in cl
ud in
g si
ck le
c el
l d is
ea se
) a nd
u nv
ac ci
na te
d pe
rs on
s 5
th ro
ug h
18 y
ea rs
o f a
ge
* Pa
tie nt
s w ho
h av
e no
t r ec
ei ve
d a
pr im
ar y
se rie
s a nd
b oo
st er
d os
e or
a t l
ea st
1 d
os e
of H
ib v
ac ci
ne a
ft er
1 4
m on
th s o
f a ge
a re
c on
si de
re d
un im
m un
iz ed
. 6.
Pn
eu m
oc oc
ca l v
ac ci
ne s.
(M in
im um
a ge
: 6 w
ee ks
fo r P
C V
13 , 2
y ea
rs fo
r P PS
V 23
) Ro
ut in
e va
cc in
at io
n w
it h
PC V
13 :
• A
dm in
is te
r a 4
-d os
e se
rie s
of P
C V1
3 va
cc in
e at
a ge
s 2,
4 , a
nd 6
m on
th s
an d
at a
ge 1
2 th
ro ug
h 15
m on
th s.
• Fo
r c hi
ld re
n ag
ed 1
4 th
ro ug
h 59
m on
th s
w ho
h av
e re
ce iv
ed a
n ag
e- ap
pr op
ria te
s er
ie s
of 7
-v al
en t P
C V
(P C
V7 ),
ad m
in is
te r a
s in
gl e
su pp
le m
en ta
l d os
e of
1 3-
va le
nt P
C V
(P C
V1 3)
. Ca
tc h-
up v
ac ci
na ti
on w
it h
PC V
13 :
• A
dm in
is te
r 1 d
os e
of P
C V1
3 to
a ll
he al
th y
ch ild
re n
ag ed
2 4
th ro
ug h
59 m
on th
s w
ho a
re n
ot c
om pl
et el
y va
cc in
at ed
fo r t
he ir
ag e.
• Fo
r o th
er c
at ch
-u p
gu id
an ce
, s ee
F ig
ur e
2.
Va cc
in at
io n
of p
er so
ns w
it h
hi gh
-r is
k co
nd it
io ns
w it
h PC
V 13
a nd
P PS
V 23
: •
A ll
re co
m m
en de
d PC
V1 3
do se
s sh
ou ld
b e
ad m
in is
te re
d pr
io r t
o PP
SV 23
v ac
ci na
tio n
if po
ss ib
le .
• Fo
r c hi
ld re
n 2
th ro
ug h
5 ye
ar s
of a
ge w
ith a
ny o
f t he
fo llo
w in
g co
nd iti
on s:
c hr
on ic
h ea
rt d
is ea
se
(p ar
tic ul
ar ly
c ya
no tic
c on
ge ni
ta l h
ea rt
d is
ea se
a nd
c ar
di ac
fa ilu
re );
ch ro
ni c
lu ng
d is
ea se
(i nc
lu di
ng
co ch
le ar
im pl
an t;
si ck
le c
el l d
is ea
se a
nd o
th er
h em
og lo
bi no
pa th
ie s;
a na
to m
ic o
r f un
ct io
na l a
sp le
ni a;
H
IV in
fe ct
io n;
c hr
on ic
re na
l f ai
lu re
; n ep
hr ot
ic s
yn dr
om e;
d is
ea se
s as
so ci
at ed
w ith
tr ea
tm en
t w ith
im
m un
os up
pr es
si ve
d ru
gs o
r r ad
ia tio
n th
er ap
y, in
cl ud
in g
m al
ig na
nt n
eo pl
as m
s, le
uk em
ia s,
ly m
ph om
as ,
1. A
dm in
is te
r 1
do se
o f P
C V1
3 if
an y
in co
m pl
et e
sc he
du le
o f 3
d os
es o
f P C
V (P
C V7
a nd
/o r
PC V1
3) w
er e
re ce
iv ed
p re
vi ou
sl y.
2. A
dm in
is te
r 2 d
os es
o f P
C V1
3 at
le as
t 8 w
ee ks
a pa
rt if
u nv
ac ci
na te
d or
a ny
in co
m pl
et e
sc he
du le
o f f
ew er
th
an 3
d os
es o
f P C
V (P
C V7
a nd
/o r P
C V1
3) w
er e
re ce
iv ed
p re
vi ou
sl y.
3. A
dm in
is te
r 1 s
up pl
em en
ta l d
os e
of P
C V1
3 if
4 do
se s
of P
C V7
o r o
th er
a ge
-a pp
ro pr
ia te
c om
pl et
e PC
V7
se rie
s w
as re
ce iv
ed p
re vi
ou sl
y. 4.
T he
m in
im um
in te
rv al
b et
w ee
n do
se s
of P
C V
(P C
V7 o
r P C
V1 3)
is 8
w ee
ks .
5. F
or c
hi ld
re n
w ith
n o
hi st
or y
of P
PS V2
3 va
cc in
at io
n, a
dm in
is te
r P PS
V2 3
at le
as t 8
w ee
ks a
ft er
th e
m os
t re
ce nt
d os
e of
P C
V1 3.
6.
Pn eu
m oc
oc ca
l v ac
ci ne
s (c
on t’d
) •
di se
as e
an d
ot he
r h em
og lo
bi no
pa th
ie s;
a na
to m
ic o
r f un
ct io
na l a
sp le
ni a;
c on
ge ni
ta l o
r a cq
ui re
d
w ith
tr ea
tm en
t w ith
im m
un os
up pr
es si
ve d
ru gs
o r r
ad ia
tio n
th er
ap y,
in cl
ud in
g m
al ig
na nt
n eo
pl as
m s,
le
uk em
ia s,
ly m
ph om
as , a
nd H
od gk
in ’s
di se
as e;
g en
er al
iz ed
m al
ig na
nc y;
s ol
id o
rg an
tr an
sp la
nt at
io n;
o r
m ul
tip le
m ye
lo m
a: 1.
I f n
ei th
er P
C V1
3 no
r P PS
V2 3
ha s
be en
re ce
iv ed
p re
vi ou
sl y,
a dm
in is
te r 1
d os
e of
P C
V1 3
no w
a nd
1 d
os e
of P
PS V2
3 at
le as
t 8 w
ee ks
la te
r. 2.
I f P
C V1
3 ha
s b ee
n re
ce iv
ed p
re vi
ou sl
y bu
t P PS
V2 3
ha s n
ot , a
dm in
is te
r 1 d
os e
of P
PS V2
3 at
le as
t 8 w
ee ks
af
te r t
he m
os t r
ec en
t d os
e of
P C
V1 3.
3. I
f P PS
V2 3
ha s
be en
re ce
iv ed
b ut
P C
V1 3
ha s
no t,
ad m
in is
te r 1
d os
e of
P C
V1 3
at le
as t 8
w ee
ks a
ft er
th e
m os
t r ec
en t d
os e
of P
PS V2
3. •
Fo r c
hi ld
re n
ag ed
6 th
ro ug
h 18
y ea
rs w
ith c
hr on
ic h
ea rt
d is
ea se
(p ar
tic ul
ar ly
c ya
no tic
c on
ge ni
ta l h
ea rt
di
se as
e an
d ca
rd ia
c fa
ilu re
), ch
ro ni
c lu
ng d
is ea
se (i
nc lu
di ng
a st
hm a
if tr
ea te
d w
ith h
ig h-
do se
o ra
l co
rt ic
os te
ro id
th er
ap y)
, d ia
be te
s m
el lit
us , a
lc oh
ol is
m , o
r c hr
on ic
li ve
r d is
ea se
, w ho
h av
e no
t r ec
ei ve
d PP
SV 23
, a dm
in is
te r 1
d os
e of
P PS
V2 3.
If P
C V1
3 ha
s be
en re
ce iv
ed p
re vi
ou sl
y, th
en P
PS V2
3 sh
ou ld
b e
ad m
in is
te re
d at
le as
t 8 w
ee ks
a ft
er a
ny p
rio r P
C V1
3 do
se .
• si
ck le
c el
l d is
ea se
o r o
th er
h em
og lo
bi no
pa th
ie s;
a na
to m
ic o
r f un
ct io
na l a
sp le
ni a;
c on
ge ni
ta l o
r a cq
ui re
d
w ith
tr ea
tm en
t w ith
im m
un os
up pr
es si
ve d
ru gs
o r r
ad ia
tio n
th er
ap y,
in cl
ud in
g m
al ig
na nt
n eo
pl as
m s,
le
uk em
ia s,
ly m
ph om
as , a
nd H
od gk
in ’s
di se
as e;
g en
er al
iz ed
m al
ig na
nc y;
s ol
id o
rg an
tr an
sp la
nt at
io n;
o r
m ul
tip le
m ye
lo m
a. 7.
In
ac ti
va te
d po
lio vi
ru s
va cc
in e
(IP V
). (M
in im
um a
ge : 6
w ee
ks )
Ro ut
in e
va cc
in at
io n:
• se
rie s s
ho ul
d be
a dm
in ist
er ed
o n
or a
fte r t
he fo
ur th
b irt
hd ay
a nd
a t l
ea st
6 m
on th
s a fte
r t he
p re
vi ou
s d os
e. Ca
tc h-
up v
ac ci
na ti
on :
• of
im m
in en
t e xp
os ur
e to
c irc
ul at
in g
po lio
vi ru
s ( i.e
., t ra
ve l t
o a
po lio
-e nd
em ic
re gi
on o
r d ur
in g
an o
ut br
ea k)
. •
If 4
or m
or e
do se
s a re
a dm
in is
te re
d be
fo re
a ge
4 y
ea rs
, a n
ad di
tio na
l d os
e sh
ou ld
b e
ad m
in is
te re
d at
a ge
4
th ro
ug h
6 ye
ar s a
nd a
t l ea
st 6
m on
th s a
fte r t
he p
re vi
ou s d
os e.
• A
fo ur
th d
os e
is n
ot n
ec es
sa ry
if th
e th
ird d
os e
w as
a dm
in is
te re
d at
a ge
4 y
ea rs
o r o
ld er
a nd
a t l
ea st
6 m
on th
s af
te r t
he p
re vi
ou s d
os e.
• If
bo th
O PV
a nd
IP V
w er
e ad
m in
is te
re d
as p
ar t o
f a se
rie s,
a to
ta l o
f 4 d
os es
sh ou
ld b
e ad
m in
is te
re d,
re ga
rd le
ss
of th
e ch
ild ’s
cu rr
en t a
ge . I
PV is
n ot
ro ut
in el
y re
co m
m en
de d
fo r U
.S . r
es id
en ts
a ge
d 18
y ea
rs o
r o ld
er .
• Fo
r o th
er c
at ch
-u p
gu id
an ce
, s ee
F ig
ur e
2. 8.
In
flu en
za v
ac ci
ne s.
(M in
im um
a ge
: 6 m
on th
s fo
r i na
ct iv
at ed
in flu
en za
v ac
ci ne
[I IV
], 2
ye ar
s fo
r l iv
e, a
tt en
ua te
d in
flu en
za v
ac ci
ne [L
A IV
])
Ro ut
in e
va cc
in at
io n:
• no
np re
gn an
t p er
so ns
a ge
d 2
th ro
ug h
49 y
ea rs
, e ith
er L
A IV
o r I
IV m
ay b
e us
ed . H
ow ev
er , L
A IV
s ho
ul d
N O
T be
a dm
in is
te re
d to
s om
e pe
rs on
s, in
cl ud
in g
1) p
er so
ns w
ho h
av e
ex pe
rie nc
ed s
ev er
e al
le rg
ic re
ac tio
ns
17 y
ea rs
re ce
iv in
g as
pi rin
o r a
sp iri
n- co
nt ai
ni ng
p ro
du ct
s; 3
) p er
so ns
w ho
a re
a lle
rg ic
to e
gg s;
4 ) p
re gn
an t
w om
en ; 5
) i m
m un
os up
pr es
se d
pe rs
on s;
6 ) c
hi ld
re n
2 th
ro ug
h 4
ye ar
s of
a ge
w ith
a st
hm a
or w
ho h
ad
pr ev
io us
4 8
ho ur
s. F
or a
ll ot
he r c
on tr
ai nd
ic at
io ns
a nd
p re
ca ut
io ns
to u
se o
f L A
IV , s
ee M
M W
R A
ug us
t 1 5,
20
14 /
63 (3
2) ;6
91 -6
97 [4
0 pa
ge s]
a va
ila bl
e at
ht
tp ://
w w
w .c
dc .g
ov /m
m w
r/ pd
f/ w
k/ m
m 63
32 .p
df .
F o r c
hi ld
re n
ag ed
6 m
on th
s th
ro ug
h 8
ye ar
s: •
Fo r t
he 2
01 4-
15 s
ea so
n, a
dm in
is te
r 2 d
os es
(s ep
ar at
ed b
y at
le as
t 4 w
ee ks
) t o
ch ild
re n
w ho
a re
re ce
iv in
g
va cc
in e
re co
m m
en da
tio ns
, M M
W R
A ug
us t 1
5, 2
01 4
/ 6 3(
32 );6
91 -6
97 [4
0 pa
ge s]
a va
ila bl
e at
h tt
p: //
w w
w .
cd c.
go v/
m m
w r/
pd f/
w k/
m m
63 32
.p df
. • Fo
r p er
so n
s ag
ed 9
y ea
rs a
n d
o ld
er :
• A
dm in
is te
r 1 d
os e.
Fo r f
ur th
er g
ui da
nc e
on th
e us
e of
th e
va cc
in es
m en
tio ne
d be
lo w
, s ee
: h tt
p: //
w w
w .c
dc .g
ov /v
ac ci
ne s/
hc p/
ac ip
-r ec
s/ in
de x.
ht m
l.
3827_Ch19_447_496 02/07/15 12:05 PM Page 457
458
Fo r f
ur th
er g
ui da
nc e
on th
e us
e of
th e
va cc
in es
m en
tio ne
d b
el ow
, s ee
: h tt
p: //
w w
w .c
dc .g
ov /v
ac ci
ne s/
hc p/
ac ip
-r ec
s/ in
de x.
ht m
l. 9.
M
ea sl
es , m
um ps
, a nd
ru be
lla (M
M R)
v ac
ci ne
. ( M
in im
um a
ge : 1
2 m
on th
s fo
r r ou
ti ne
va
cc in
at io
n) Ro
ut in
e va
cc in
at io
n: •
A dm
in is
te r a
2 -d
os e
se rie
s of
M M
R va
cc in
e at
a ge
s 12
th ro
ug h
15 m
on th
s an
d 4
th ro
ug h
6 ye
ar s.
Th e
do se
. •
A dm
in is
te r 1
d os
e of
M M
R va
cc in
e to
in fa
nt s
ag ed
6 th
ro ug
h 11
m on
th s
be fo
re d
ep ar
tu re
fr om
th e
U ni
te d
at a
ge 1
2 th
ro ug
h 15
m on
th s
(1 2
m on
th s
if th
e ch
ild re
m ai
ns in
a n
ar ea
w he
re d
is ea
se ri
sk is
h ig
h) , a
nd th
e se
co nd
d os
e at
le as
t 4 w
ee ks
la te
r. •
A dm
in is
te r 2
d os
es o
f M M
R va
cc in
e to
c hi
ld re
n ag
ed 1
2 m
on th
s an
d ol
de r b
ef or
e de
pa rt
ur e
fr om
th e
th e
se co
nd d
os e
at le
as t 4
w ee
ks la
te r.
Ca tc
h- up
v ac
ci na
ti on
: •
En su
re th
at a
ll sc
ho ol
-a ge
d ch
ild re
n an
d ad
ol es
ce nt
s ha
ve h
ad 2
d os
es o
f M M
R va
cc in
e; th
e m
in im
um
in te
rv al
b et
w ee
n th
e 2
do se
s is
4 w
ee ks
. 10
. Va
ri ce
lla (V
A R)
v ac
ci ne
. ( M
in im
um a
ge : 1
2 m
on th
s)
Ro ut
in e
va cc
in at
io n:
• A
dm in
is te
r a 2
-d os
e se
rie s
of V
A R
va cc
in e
at a
ge s
12 th
ro ug
h 15
m on
th s
an d
4 th
ro ug
h 6
ye ar
s. T
he
se co
nd d
os e
m ay
b e
ad m
in is
te re
d be
fo re
a ge
4 y
ea rs
, p ro
vi de
d at
le as
t 3 m
on th
s ha
ve e
la ps
ed s
in ce
th e
va lid
. Ca
tc h-
up v
ac ci
na ti
on :
• En
su re
th at
a ll
pe rs
on s
ag ed
7 th
ro ug
h 18
y ea
rs w
ith ou
t e vi
de nc
e of
im m
un ity
(s ee
M M
W R
20 07
/ 56
[N o.
RR
-4 ],
av ai
la bl
e at
h tt
p: //
w w
w .c
dc .g
ov /m
m w
r/ pd
f/ rr
/r r5
60 4.
pd f )
h av
e 2
do se
s of
v ar
ic el
la v
ac ci
ne .
Fo r
ch ild
r e n
ag ed
7 th
ro ug
h 12
y ea
rs , t
he re
co m
m en
de d
m in
im um
in te
rv al
b et
w ee
n do
se s
is 3
m on
th s
(if
pe rs
on s
ag ed
1 3
ye ar
s an
d ol
de r,
th e
m in
im um
in te
rv al
b et
w ee
n do
se s
is 4
w ee
ks .
11 .
H ep
at it
is A
(H ep
A ) v
ac ci
ne . (
M in
im um
a ge
: 1 2
m on
th s)
Ro ut
in e
va cc
in at
io n:
• In
iti at
e th
e 2-
do se
H ep
A v
ac ci
ne s
er ie
s at
1 2
th ro
ug h
23 m
on th
s; s
ep ar
at e
th e
2 do
se s
by 6
to 1
8 m
on th
s. •
C hi
ld re
n w
ho h
av e
re ce
iv ed
1 d
os e
of H
ep A
v ac
ci ne
b ef
or e
ag e
24 m
on th
s sh
ou ld
re ce
iv e
a se
co nd
d os
e
• Fo
r a ny
p er
so n
ag ed
2 y
ea rs
a nd
o ld
er w
ho h
as n
ot a
lre ad
y re
ce iv
ed th
e H
ep A
v ac
ci ne
s er
ie s,
2 d
os es
o f
H ep
A v
ac ci
ne s
ep ar
at ed
b y
6 to
1 8
m on
th s
m ay
b e
ad m
in is
te re
d if
im m
un ity
a ga
in st
h ep
at iti
s A
v iru
s in
fe ct
io n
is d
es ire
d.
Ca tc
h- up
v ac
ci na
ti on
: •
Th e
m in
im um
in te
rv al
b et
w ee
n th
e tw
o do
se s
is 6
m on
th s.
Sp
ec ia
l p op
ul at
io ns
: •
A dm
in is
te r 2
d os
es o
f H ep
A v
ac ci
ne a
t l ea
st 6
m on
th s
ap ar
t t o
pr ev
io us
ly u
nv ac
ci na
te d
pe rs
on s
w ho
liv
e in
a re
as w
he re
v ac
ci na
tio n
pr og
ra m
s ta
rg et
o ld
er c
hi ld
re n,
o r w
ho a
re a
t i nc
re as
ed ri
sk fo
r i nf
ec tio
n.
Th is
in cl
ud es
p er
so ns
tr av
el in
g to
o r w
or ki
ng in
c ou
nt rie
s th
at h
av e
hi gh
o r i
nt er
m ed
ia te
e nd
em ic
ity o
f in
fe ct
io n;
m en
h av
in g
se x
w ith
m en
; u se
rs o
f i nj
ec tio
n an
d no
n- in
je ct
io n
ill ic
it dr
ug s;
p er
so ns
w ho
w or
k w
ith H
AV -in
fe ct
ed p
rim at
es o
r w ith
H AV
in a
re se
ar ch
la bo
ra to
ry ; p
er so
ns w
ith c
lo tt
in g-
fa ct
or d
is or
de rs
; pe
rs on
s w
ith c
hr on
ic li
ve r d
is ea
se ; a
nd p
er so
ns w
ho a
nt ic
ip at
e cl
os e
pe rs
on al
c on
ta ct
(e .g
., ho
us eh
ol d
so on
a s
th e
ad op
tio n
is p
la nn
ed , i
de al
ly 2
o r m
or e
w ee
ks b
ef or
e th
e ar
riv al
o f t
he a
do pt
ee .
12 .
H um
an p
ap ill
om av
ir us
(H PV
) v ac
ci ne
s. (
M in
im um
a ge
: 9
ye ar
s fo
r H PV
2 [C
er va
ri x]
an
d H
PV 4
[G ar
da si
l])
Ro ut
in e
va cc
in at
io n:
• A
dm in
is te
r a 3
-d os
e se
rie s
of H
PV v
ac ci
ne o
n a
sc he
du le
o f 0
, 1 -2
, a nd
6 m
on th
s to
a ll
ad ol
es ce
nt s
ag ed
1 1
th ro
ug h
12 y
ea rs
. E ith
er H
PV 4
or H
PV 2
m ay
b e
us ed
fo r f
em al
es , a
nd o
nl y
H PV
4 m
ay b
e us
ed fo
r m al
es .
• Th
e va
cc in
e se
rie s
m ay
b e
st ar
te d
at a
ge 9
y ea
rs .
• Ca tc
h- up
v ac
ci na
ti on
: •
A dm
in is
te r t
he v
ac ci
ne s
er ie
s to
fe m
al es
(e ith
er H
PV 2
or H
PV 4)
a nd
m al
es (H
PV 4)
a t a
ge 1
3 th
ro ug
h 18
ye
ar s
if no
t p re
vi ou
sl y
va cc
in at
ed .
• U
se re
co m
m en
de d
ro ut
in e
do si
ng in
te rv
al s
(s ee
R ou
tin e
va cc
in at
io n
ab ov
e) fo
r v ac
ci ne
s er
ie s
ca tc
h- up
.
13 .
M en
in go
co cc
al c
on ju
ga te
v ac
ci ne
s. (M
in im
um a
ge : 6
w ee
ks fo
r H ib
-M en
C Y
[M en
H ib
ri x]
, 9 m
on th
s fo
r M en
A C
W Y-
D [M
en ac
tr a]
, 2 m
on th
s fo
r M en
A C
W Y-
C RM
[M
en ve
o] )
Ro ut
in e
va cc
in at
io n:
• A
dm in
is te
r a s
in gl
e do
se o
f M en
ac tr
a or
M en
ve o
va cc
in e
at a
ge 1
1 th
ro ug
h 12
y ea
rs , w
ith a
b oo
st er
d os
e at
a ge
1 6
ye ar
s. •
re ce
iv e
a 2-
do se
p rim
ar y
se rie
s of
M en
ac tr
a or
M en
ve o
w ith
a t l
ea st
8 w
ee ks
b et
w ee
n do
se s.
• Fo
r c hi
ld re
n ag
ed 2
m on
th s
th ro
ug h
18 y
ea rs
w ith
h ig
h- ris
k co
nd iti
on s,
s ee
b el
ow .
Ca tc
h- up
v ac
ci na
ti on
: •
A dm
in is
te r M
en ac
tr a
or M
en ve
o va
cc in
e at
a ge
1 3
th ro
ug h
18 y
ea rs
if n
ot p
re vi
ou sl
y va
cc in
at ed
. •
16 th
ro ug
h 18
y ea
rs w
ith a
m in
im um
in te
rv al
o f a
t l ea
st 8
w ee
ks b
et w
ee n
do se
s. • •
Fo r o
th er
c at
ch -u
p gu
id an
ce , s
ee F
ig ur
e 2.
Va cc
in at
io n
of p
er so
ns w
it h
hi gh
-r is
k co
nd it
io ns
a nd
o th
er p
er so
ns a
t i nc
re as
ed ri
sk o
f d is
ea se
: •
C hi
ld re
n w
ith a
na to
m ic
o r f
un ct
io na
l a sp
le ni
a (in
cl ud
in g
si ck
le c
el l d
is ea
se ):
1. M
en ve
o
o Ch
ild re
n w
ho in
iti at
e v ac
ci na
tio n
at 8
w ee
ks th
ro ug
h 6
m on
th s:
A dm
in is
te r d
os es
a t 2
, 4 , 6
, a nd
1 2
m on
th s
of a
ge .
o U
nv ac
ci na
te d
ch ild
re n
7 th
ro ug
h 23
m on
th s:
A dm
in is
te r 2
d os
es , w
ith th
e se
co nd
d os
e at
le as
t 1 2
w ee
ks
o Ch
ild re
n 24
m on
th s
an d
ol de
r w ho
h av
e no
t r ec
ei ve
d a
co m
pl et
e se
rie s:
A dm
in is
te r 2
p rim
ar y
do se
s at
le
as t 8
w ee
ks a
pa rt
. 2.
M en
H ib
rix o
Ch ild
re n
6 w
ee ks
th ro
ug h
18 m
on th
s: A
dm in
is te
r d os
es a
t 2 , 4
, 6 , a
nd 1
2 th
ro ug
h 15
m on
th s
of a
ge .
o at
le as
t 8 w
ee ks
a pa
rt to
e ns
ur e
pr ot
ec tio
n ag
ai ns
t s er
og ro
up s
C a
nd Y
m en
in go
co cc
al d
is ea
se .
3. M
en ac
tr a
o Ch
ild re
n 24
m on
th s a
nd o
ld er
w ho
h av
e no
t r ec
ei ve
d a
co m
pl et
e se
rie s:
A dm
in is
te r 2
p rim
ar y
do se
s at
le
as t 8
w ee
ks a
pa rt
. I f M
en ac
tr a
is a
dm in
is te
re d
to a
c hi
ld w
ith a
sp le
ni a
(in cl
ud in
g si
ck le
c el
l d is
ea se
), do
n ot
a dm
in is
te r M
en ac
tr a
un til
2 y
ea rs
o f a
ge a
nd a
t l ea
st 4
w ee
ks a
ft er
th e
co m
pl et
io n
of a
ll PC
V1 3
do se
s. •
1. M
en ve
o o
Ch ild
re n
w ho
in iti
at e v
ac ci
na tio
n at
8 w
ee ks
th ro
ug h
6 m
on th
s: A
dm in
is te
r d os
es a
t 2 , 4
, 6 , a
nd 1
2 m
on th
s of
a ge
. o
U nv
ac ci
na te
d ch
ild re
n 7
th ro
ug h
23 m
on th
s: A
dm in
is te
r 2 d
os es
, w ith
th e
se co
nd d
os e
at le
as t 1
2 w
ee ks
o Ch
ild re
n 24
m on
th s a
nd o
ld er
w ho
h av
e no
t r ec
ei ve
d a
co m
pl et
e se
rie s:
A dm
in is
te r 2
p rim
ar y
do se
s at
le
as t 8
w ee
ks a
pa rt
. 2.
M en
H ib
rix o
Ch ild
re n
6 w
ee ks
th ro
ug h
18 m
on th
s: A
dm in
is te
r d os
es a
t 2 , 4
, 6 , a
nd 1
2 th
ro ug
h 15
m on
th s
of a
ge .
o at
le as
t 8 w
ee ks
a pa
rt to
e ns
ur e
pr ot
ec tio
n ag
ai ns
t s er
og ro
up s
C a
nd Y
m en
in go
co cc
al d
is ea
se .
3. M
en ac
tr a
o Ch
ild re
n 9
th ro
ug h
23 m
on th
s: A
dm in
is te
r 2 p
rim ar
y do
se s
at le
as t 1
2 w
ee ks
a pa
rt .
o Ch
ild re
n 24
m on
th s
an d
ol de
r w ho
h av
e no
t r ec
ei ve
d a
co m
pl et
e se
rie s:
A dm
in is
te r 2
p rim
ar y
do se
s at
le
as t 8
w ee
ks a
pa rt
. •
Fo r c
hi ld
re n
w ho
tr av
el to
o r r
es id
e in
c ou
nt rie
s in
w hi
ch m
en in
go co
cc al
d is
ea se
is h
yp er
en de
m ic
o r
ep id
em ic
, i nc
lu di
ng c
ou nt
rie s
in th
e A
fr ic
an m
en in
gi tis
b el
t o r t
he H
aj j,
ad m
in is
te r a
n ag
e- ap
pr op
ria te
fo
rm ul
at io
n an
d se
rie s
of M
en ac
tr a
or M
en ve
o fo
r p ro
te ct
io n
ag ai
ns t s
er og
ro up
s A
a nd
W m
en in
go co
cc al
be ca
us e
it do
es n
ot c
on ta
in s
er og
ro up
s A
o r W
. •
Fo r c
hi ld
re n
at ri
sk d
ur in
g a
co m
m un
ity o
ut br
ea k
at tr
ib ut
ab le
to a
v ac
ci ne
s er
og ro
up , a
dm in
is te
r o r
co m
pl et
e an
a ge
- a nd
fo rm
ul at
io n-
ap pr
op ria
te s
er ie
s of
M en
H ib
rix , M
en ac
tr a,
o r M
en ve
o. •
Fo r b
oo st
er d
os es
a m
on g
pe rs
on s
w ith
h ig
h- ris
k co
nd iti
on s,
re fe
r t o
M M
W R
20 13
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3827_Ch19_447_496 02/07/15 12:05 PM Page 458
459
Table 19–3 Vaccine Information Statements
MEASLES, MUMPS, RUBELLA, AND VARICELLA VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Patient Education
ORAL POLIOVIRUS VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
460
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Patient Education
ROTAVIRUS VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
461
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Drug Interactions
Clinical Use and Dosing
Patient Education
VARICELLA VIRUS VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
462
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
463
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Monitoring
Patient Education
ZOSTER VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
464
CLINICAL PEARL
Administering Multiple Vaccines Currently a child from age 12 to 18 months should re- ceive six possible injections. This can be traumatic for patient and parent. Most public health officials recom- mend giving all the recommended vaccines at one visit; therefore, the child who is 15 months old could be getting as many as all six injections at that visit. Using combined vaccines is best (Pediarix, Pentacel) to decrease the number of injections or spread the administration of the vaccines over two or three visits. If it is necessary to give all the vaccines in one visit, as in the case of upcoming international travel or a history of unreliable attendance at well-child examinations, two people can administer the vaccines simultane- ously. Giving the vaccines simultaneously makes the process faster and simpler for the patient and the per- son administering the vaccine. The CDC guidelines for administering multiple injections to infants are located in Appendix D of the Pink Book at www.cdc.gov/ vaccines/pubs/pinkbook/index.html.
3827_Ch19_447_496 02/07/15 12:05 PM Page 464
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
ORAL TYPHOID VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
465
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466
*Covered by the Vaccine Injury Compensation Program
For all persons in this category who meet the age requirements and who lack documentation of vaccination or have no evidence of previous infection; zoster vaccine recommended regardless of prior episode of zoster
Recommended if some other risk factor is present (e.g., on the basis of medical, occupational, lifestyle, or other indication)
No recommendation
Recommended Adult Immunization Schedule—United States - 2015 Note: These recommendations must be read with the footnotes that follow
containing number of doses, intervals between doses, and other important information.
Figure 1. Recommended adult immunization schedule, by vaccine and age group1
report are available at www.vaers.hhs.gov or by telephone, 800-822-7967.
www.hrsa.gov/vaccinecompensation claim for vaccine injury, contact the U.S. Court of Federal Claims, 717 Madison Place, N.W., Washington, D.C. 20005; telephone, 202-357-6400.
Additional information about the vaccines in this schedule, extent of available data, and contraindications for vaccination is also available at www.cdc.gov/vaccines or from the CDC-INFO Contact Center at 800-CDC-INFO (800-232-4636) in English and Spanish, 8:00 a.m. - 8:00 p.m. Eastern Time, Monday - Friday, excluding holidays.
The recommendations in this schedule were approved by the Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP), the American Academy of Family Physicians (AAFP), the America College of Physicians (ACP), American College of Obstetricians and Gynecologists (ACOG) and American College of Nurse-Midwives (ACNM).
Figure 2. Vaccines that might be indicated for adults based on medical and other indications1
VACCINE AGE GROUP 19-21 years 22-26 years 27-49 years 50-59 years 60-64 years ≥ 65 years
3 doses
1 or 3 doses
2 doses
1 or more doses
1 dose1 or 2 doses
1 or 2 doses
1 dose
3 doses
2 doses
Substitute 1-time dose of Tdap for Td booster; then boost with Td every 10 yrs
1 dose annually
VACCINE INDICATION Pregnancy
Immuno- compromising
conditions (excluding human
virus [HIV]) 4,6,7,8,13
HIV infection CD4+ T lymphocyte
count 4,6,7,8,13 Men who have sex
with men (MSM)
Kidney failure, end-stage renal
disease, receipt of hemodialysis
Heart disease, chronic
lung disease, chronic
alcoholism
Asplenia (including elective splenectomy
and persistent complement component
8,12
Chronic liver
disease Diabetes Healthcare personnel
< 200 cells/ L
≥ 200 cells/ L
These schedules indicate the recommended age groups and medical indications for which administration of currently licensed vaccines is commonly recommended for adults ages 19 years and older, as of February 1, 2015. For all vaccines being recommended on the Adult Immunization Schedule: a vaccine series does not need to be restarted, regardless of the time that has elapsed between doses. Licensed combination vaccines may be used whenever any components of the combination are indicated and when the vaccine’s other components are not contraindicated. For detailed recommendations on all vaccines, including those used primarily for travelers or that are issued during the year, consult the manufacturers’ package inserts and the complete statements from the Advisory Committee on Immunization Practices (www.cdc.gov/vaccines/hcp/acip-recs/index.html imply endorsement by the U.S. Department of Health and Human Services.
3 doses
1 or 3 doses
2 doses
1 or more doses
1 dose
1 or 2 doses
1 or 2 dosesContraindicated
1 doseContraindicated
3 doses through age 21 yrs3 doses through age 26 yrs
3 doses through age 26 yrs3 doses through age 26 yrs
2 dosesContraindicated
Substitute 1-time dose of Tdap for Td booster; then boost with Td every 10 yrs
1 does IIV or LAIV annually1 dose IIV annually
1 dose IIV or LAIV annually
1 dose Tdap each pregnancy
1 dose IIV annually
post-HSCT recipients only
For all persons in this category who meet the age requirements and who lack documentation of vaccination or have no evidence of previous infection; zoster vaccine recommended regardless of prior episode of zoster
Recommended if some other risk factor is present (e.g., on the basis of medical, occupational, lifestyle, or other indications)
No recommendation*Covered by the Vaccine Injury Compensation Program
3 doses
1-time dose
Table 19–4 ! Recommended Adult Immunization Schedule – United States, 2015
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467
Table 19–4 ! Recommended Adult Immunization Schedule – United States, 2015—cont’d
1. Additional information • Additional guidance for the use of the vaccines described in this supplement is
available at www.cdc.gov/vaccines/hcp/acip-recs/index.html. • Information on vaccination recommendations when vaccination status is
unknown and other general immunization information can be found in the General Recommendations on Immunization at www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm.
• Information on travel vaccine requirements and recommendations (e.g., for hepatitis A and B, meningococcal, and other vaccines) is available at wwwnc.cdc.gov/travel/destinations/list.
• Additional information and resources regarding vaccination of pregnant women can be found at www.cdc.gov/vaccines/adults/rec-vac/pregnant.html.
2. Influenza vaccination •
months or older. • Persons aged 6 months or older, including pregnant women and persons with
age-appropriate IIV formulation should be used. •
(RIV) (FluBlok). RIV does not contain any egg protein and can be given to age- appropriate persons with egg allergy of any severity.
• Healthy, nonpregnant persons aged 2 to 49 years without high-risk medical conditions can receive either intranasally administered live, attenuated
• Health care personnel who care for severely immunocompromised persons who require care in a protected environment should receive IIV or RIV; health care personnel who receive LAIV should avoid providing care for severely immunosuppressed persons for 7 days after vaccination.
• The intramuscularly or intradermally administered IIV are options for adults aged 18 through 64 years.
• Adults aged 65 years or older can receive the standard-dose IIV or the high- dose IIV (Fluzone High-Dose).
• .
3. Tetanus, diphtheria, and acellular pertussis (Td/Tdap) vaccination • Administer 1 dose of Tdap vaccine to pregnant women during each pregnancy
(preferably during 27 to 36 weeks’ gestation) regardless of interval since prior Td or Tdap vaccination.
• Persons aged 11 years or older who have not received Tdap vaccine or for whom vaccine status is unknown should receive a dose of Tdap followed by tetanus and diphtheria toxoids (Td) booster doses every 10 years thereafter. Tdap can be administered regardless of interval since the most recent tetanus or diphtheria-toxoid containing vaccine.
• Adults with an unknown or incomplete history of completing a 3-dose primary vaccination series with Td-containing vaccines should begin or complete a primary vaccination series including a Tdap dose.
• the third dose 6 to 12 months after the second.
• For incompletely vaccinated (i.e., less than 3 doses) adults, administer remaining doses.
• Refer to the ACIP statement for recommendations for administering Td/Tdap as prophylaxis in wound management (see footnote 1).
4. Varicella vaccination •
receive 2 doses of single-antigen varicella vaccine or a second dose if they have received only 1 dose.
• Vaccination should be emphasized for those who have close contact with persons at high risk for severe disease (e.g., health care personnel and family contacts of persons with immunocompromising conditions) or are at high risk for exposure or transmission (e.g., teachers; child care employees;
institutions; college students; military personnel; adolescents and adults living in households with children; nonpregnant women of childbearing age; and international travelers).
• Pregnant women should be assessed for evidence of varicella immunity.
of varicella vaccine upon completion or termination of pregnancy and before discharge from the health care facility. The second dose should be administered
• Evidence of immunity to varicella in adults includes any of the following: documentation of 2 doses of varicella vaccine at least 4 weeks apart; U.S.-born before 1980, except health care personnel and pregnant women;
a health care provider;
disease by a health care provider; or
5. Human papillomavirus (HPV) vaccination • Two vaccines are licensed for use in females, bivalent HPV vaccine (HPV2) and
quadrivalent HPV vaccine (HPV4), and one HPV vaccine for use in males (HPV4). • For females, either HPV4 or HPV2 is recommended in a 3-dose series for routine
vaccination at age 11 or 12 years and for those aged 13 through 26 years, if not previously vaccinated.
• For males, HPV4 is recommended in a 3-dose series for routine vaccination at age 11 or 12 years and for those aged 13 through 21 years, if not previously vaccinated. Males aged 22 through 26 years may be vaccinated.
• HPV4 is recommended for men who have sex with men through age 26 years for those who did not get any or all doses when they were younger.
• Vaccination is recommended for immunocompromised persons (including those with HIV infection) through age 26 years for those who did not get any or all doses when they were younger.
• A complete series for either HPV4 or HPV2 consists of 3 doses. The second dose should be administered 4 to 8 weeks (minimum interval of 4 weeks) after the
and 16 weeks after the second dose (minimum interval of at least 12 weeks). • HPV vaccines are not recommended for use in pregnant women. However,
pregnancy testing is not needed before vaccination. If a woman is found to be pregnant after initiating the vaccination series, no intervention is needed; the remainder of the 3-dose series should be delayed until completion or termination of pregnancy.
6. Zoster vaccination • A single dose of zoster vaccine is recommended for adults aged 60 years
or older regardless of whether they report a prior episode of herpes zoster. Although the vaccine is licensed by the U.S. Food and Drug Administration for use among and can be administered to persons aged 50 years or older, ACIP recommends that vaccination begin at age 60 years.
• Persons aged 60 years or older with chronic medical conditions may be vaccinated unless their condition constitutes a contraindication, such as
7. Measles, mumps, rubella (MMR) vaccination • Adults born before 1957 are generally considered immune to measles and
mumps. All adults born in 1957 or later should have documentation of 1 or more doses of MMR vaccine unless they have a medical contraindication to the vaccine or laboratory evidence of immunity to each of the three diseases. Documentation of provider-diagnosed disease is not considered acceptable evidence of immunity for measles, mumps, or rubella.
Measles component: • A routine second dose of MMR vaccine, administered a minimum of 28 days
are students in postsecondary educational institutions, work in a health care facility, or plan to travel internationally.
• Persons who received inactivated (killed) measles vaccine or measles vaccine of unknown type during 1963–1967 should be revaccinated with 2 doses of MMR vaccine.
Mumps component: • A routine second dose of MMR vaccine, administered a minimum of 28 days
are students in a postsecondary educational institution, work in a health care facility, or plan to travel internationally.
• Persons vaccinated before 1979 with either killed mumps vaccine or mumps vaccine of unknown type who are at high risk for mumps infection (e.g., persons who are working in a health care facility) should be considered for revaccination with 2 doses of MMR vaccine.
Rubella component: • For women of childbearing age, regardless of birth year, rubella immunity
should be determined. If there is no evidence of immunity, women who are not pregnant should be vaccinated. Pregnant women who do not have evidence of immunity should receive MMR vaccine upon completion or termination of pregnancy and before discharge from the health care facility.
Health care personnel born before 1957: • For unvaccinated health care personnel born before 1957 who lack laboratory
evidence of measles, mumps, and/or rubella immunity or laboratory
personnel with 2 doses of MMR vaccine at the appropriate interval for measles and mumps or 1 dose of MMR vaccine for rubella.
8. Pneumococcal (13-valent pneumococcal conjugate vaccine [PCV13] and 23-valent pneumococcal polysaccharide vaccine [PPSV23]) vaccination • General information
When indicated, only a single dose of PCV13 is recommended for adults. No additional dose of PPSV23 is indicated for adults vaccinated with PPSV23 at or after age 65 years. When both PCV13 and PPSV23 are indicated, PCV13 should be
the same visit. When indicated, PCV13 and PPSV23 should be administered to adults whose pneumococcal vaccination history is incomplete or unknown.
• Adults aged 65 years or older who Have not received PCV13 or PPSV23: Administer PCV13 followed by PPSV23 in 6 to 12 months. Have not received PCV13 but have received a dose of PPSV23 at age 65 years or older: Administer PCV13 at least 1 year after the dose of PPSV23 received at age 65 years or older.
Footnotes—Recommended Immunization Schedule for Adults Aged 19 Years or Older: United States, 2015
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468
Table 19–4 ! Recommended Adult Immunization Schedule – United States, 2015—cont’d
8. Pneumococcal vaccination (continued) Have not received PCV13 but have received 1 or more doses of PPSV23
before age 65: Administer PCV13 at least 1 year after the most recent dose of PPSV23; administer a dose of PPSV23 6 to 12 months after PCV13, or as soon as possible if this time window has passed, and at least 5 years after the most recent dose of PPSV23.
Have received PCV13 but not PPSV23 before age 65 years: Administer PPSV23 6 to 12 months after PCV13 or as soon as possible if this time window has passed.
Have received PCV13 and 1 or more doses of PPSV23 before age 65 years: Administer PPSV23 6 to 12 months after PCV13, or as soon as possible if this time window has passed, and at least 5 years after the most recent dose of PPSV23.
• Adults aged 19 through 64 years with immunocompromising conditions or
Have not received PCV13 or PPSV23: Administer PCV13 followed by PPSV23 at least 8 weeks after PCV13; administer a second dose of PPSV23 at least 5
Have not received PCV13 but have received 1 dose of PPSV23: Administer PCV13 at least 1 year after the PPSV23; administer a second dose of PPSV23
PPSV23. Have not received PCV13 but have received 2 doses of PPSV23: Administer
PCV13 at least 1 year after the most recent dose of PPSV23. Have received PCV13 but not PPSV23: Administer PPSV23 at least 8 weeks
after PCV13; administer a second dose of PPSV23 at least 5 years after the
Have received PCV13 and 1 dose of PPSV23: Administer a second dose of
• implants: Administer PCV13 followed by PPSV23 at least 8 weeks after PCV13.
• Adults aged 19 through 64 years with chronic heart disease (including congestive heart failure and cardiomyopathies, excluding hypertension), chronic lung disease (including chronic obstructive lung disease, emphysema, and asthma), chronic liver disease (including cirrhosis), alcoholism, or diabetes mellitus: Administer PPSV23.
• Adults aged 19 through 64 years who smoke cigarettes or reside in nursing home or long-term care facilities: Administer PPSV23.
• Routine pneumococcal vaccination is not recommended for American Indian/ Alaska Native or other adults unless they have the indications as above; however, public health authorities may consider recommending the use of pneumococcal vaccines for American Indians/Alaska Natives or other adults who live in areas with increased risk for invasive pneumococcal disease.
• Immunocompromising conditions that are indications for pneumococcal
excluding chronic granulomatous disease), HIV infection, chronic renal failure, nephrotic syndrome, leukemia, lymphoma, Hodgkin disease, generalized malignancy, multiple myeloma, solid organ transplant, and iatrogenic immunosuppression (including long-term systemic corticosteroids and radiation therapy).
• Anatomical or functional asplenia that are indications for pneumococcal vaccination are: Sickle cell disease and other hemoglobinopathies, congenital or acquired asplenia, splenic dysfunction, and splenectomy. Administer pneumococcal vaccines at least 2 weeks before immunosuppressive therapy or an elective splenectomy, and as soon as possible to adults who are newly diagnosed with asymptomatic or symptomatic HIV infection.
9. Meningococcal vaccination • Administer 2 doses of quadrivalent meningococcal conjugate vaccine
(MenACWY [Menactra, Menveo]) at least 2 months apart to adults of all ages with anatomical or functional asplenia or persistent complement component
MenACWY. If an HIV-infected person of any age is vaccinated, 2 doses of MenACWY should be administered at least 2 months apart.
• Administer a single dose of meningococcal vaccine to microbiologists routinely exposed to isolates of Neisseria meningitidis, military recruits, persons at risk during an outbreak attributable to a vaccine serogroup, and persons who travel to or live in countries in which meningococcal disease is hyperendemic or epidemic.
• First-year college students up through age 21 years who are living in residence halls should be vaccinated if they have not received a dose on or after their 16th birthday.
• MenACWY is preferred for adults with any of the preceding indications who are aged 55 years or younger as well as for adults aged 56 years or older who a) were vaccinated previously with MenACWY and are recommended for revaccination, or b) for whom multiple doses are anticipated. Meningococcal polysaccharide vaccine (MPSV4 [Menomune]) is preferred for adults aged 56 years or older who have not received MenACWY previously and who require a single dose only (e.g., travelers).
• Revaccination with MenACWY every 5 years is recommended for adults previously vaccinated with MenACWY or MPSV4 who remain at increased risk for infection (e.g., adults with anatomical or functional asplenia, persistent
10. Hepatitis A vaccination • Vaccinate any person seeking protection from hepatitis A virus (HAV) infection
and persons with any of the following indications: men who have sex with men and persons who use injection or
noninjection illicit drugs; persons working with HAV-infected primates or with HAV in a research
laboratory setting; persons with chronic liver disease and persons who receive clotting factor
concentrates; persons traveling to or working in countries that have high or intermediate
endemicity of hepatitis A; and unvaccinated persons who anticipate close personal contact (e.g.,
household or regular babysitting) with an international adoptee during
or intermediate endemicity. (See footnote 1 for more information on travel
should be administered as soon as adoption is planned, ideally 2 or more weeks before the arrival of the adoptee.
• Single-antigen vaccine formulations should be administered in a 2-dose schedule at either 0 and 6 to 12 months (Havrix), or 0 and 6 to 18 months (Vaqta). If the combined hepatitis A and hepatitis B vaccine (Twinrix) is used, administer 3 doses at 0, 1, and 6 months; alternatively, a 4-dose schedule may be used, administered on days 0, 7, and 21 to 30 followed by a booster dose at month 12.
11. Hepatitis B vaccination • Vaccinate persons with any of the following indications and any person seeking
protection from hepatitis B virus (HBV) infection: sexually active persons who are not in a long-term, mutually monogamous
relationship (e.g., persons with more than 1 sex partner during the previous 6 months); persons seeking evaluation or treatment for a sexually transmitted disease (STD); current or recent injection drug users; and men who have sex with men;
health care personnel and public safety workers who are potentially
persons with diabetes who are younger than age 60 years as soon as feasible after diagnosis; persons with diabetes who are age 60 years or older at the discretion of the treating clinician based on the likelihood of acquiring HBV infection, including the risk posed by an increased need for assisted blood glucose monitoring in long-term care facilities, the likelihood of experiencing chronic sequelae if infected with HBV, and the likelihood of immune response to vaccination;
persons with end-stage renal disease, including patients receiving hemodialysis, persons with HIV infection, and persons with chronic liver disease;
household contacts and sex partners of hepatitis B surface antigen–
developmental disabilities, and international travelers to countries with high or intermediate prevalence of chronic HBV infection; and
all adults in the following settings: STD treatment facilities, HIV testing and treatment facilities, facilities providing drug abuse treatment and prevention services, health care settings targeting services to injection drug users or men who have sex with men, correctional facilities, end-stage renal disease programs and facilities for chronic hemodialysis patients, and institutions and nonresidential day care facilities for persons with developmental disabilities.
• Administer missing doses to complete a 3-dose series of hepatitis B vaccine to those persons not vaccinated or not completely vaccinated. The second dose
given at least 2 months after the second dose (and at least 4 months after the
give 3 doses at 0, 1, and 6 months; alternatively, a 4-dose Twinrix schedule, administered on days 0, 7, and 21 to 30 followed by a booster dose at month 12 may be used.
• Adult patients receiving hemodialysis or with other immunocompromising conditions should receive 1 dose of 40 mcg/mL (Recombivax HB) administered on a 3-dose schedule at 0, 1, and 6 months or 2 doses of 20 mcg/mL (Engerix-B) administered simultaneously on a 4-dose schedule at 0, 1, 2, and 6 months.
12. type b (Hib) vaccination • One dose of Hib vaccine should be administered to persons who have
anatomical or functional asplenia or sickle cell disease or are undergoing elective splenectomy if they have not previously received Hib vaccine. Hib vaccination 14 or more days before splenectomy is suggested.
• Recipients of a hematopoietic stem cell transplant (HSCT) should be vaccinated with a 3-dose regimen 6 to 12 months after a successful transplant, regardless of vaccination history; at least 4 weeks should separate doses.
• Hib vaccine is not recommended for adults with HIV infection since their risk for Hib infection is low.
13. Immunocompromising conditions • Inactivated vaccines generally are acceptable (e.g., pneumococcal,
www.cdc.gov/vaccines/hcp/acip-recs/index.html.
Footnotes—Recommended Immunization Schedule for Adults Aged 19 Years or Older: United States, 2015
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
YELLOW FEVER VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
469
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
BACILLUS CALMETTEGUÉRIN VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
470
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Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
INACTIVATED VACCINES DIPHTHERIA, TETANUS, AND PERTUSSIS VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
471
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
472
3827_Ch19_447_496 02/07/15 12:05 PM Page 472
Monitoring
Patient Education
B CONJUGATE VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
INACTIVATED POLIOVIRUS VACCINE
Pharmacodynamics
473
CLINICAL PEARL
Patients With Shot Phobia In older children and adults who have a true phobia of injections, use EMLA cream to anesthetize the injection area. Have the patient apply the disk or cream 1 hour prior to the scheduled administration time, or the cream can be applied in the clinic and the injection adminis- tered after 1 hour.
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Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
HEPATITIS B VIRUS VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
474
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475
CLINICAL PEARL
Administering Injections A technique to help older children, adolescents, or adults who are anxious about receiving injections is to encourage them to take slow, deep breaths. Younger children (5-year-olds) can be told to pretend they are blowing up a balloon. Have the patient inhale and ex- hale two or three times, and then, on the third or fourth exhalation, administer the injection.
Table 19–5 ! Recommended Doses of Currently Licensed Formulations of Hepatitis B Vaccine by Age Group and Vaccine Type
Single-Antigen Combination Vaccine Vaccine
x§
Volume Dose Volume Dose Volume Dose Volume Dose Volume Age Group Dose (mcg) (mL) (mcg) (mL) (mcg) (mL) (mcg) (mL) (mcg) (mL)
Adolescents
Hemodialysis Patients and Other Immunocompromised Persons
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Monitoring
Patient Education
HEPATITIS A VIRUS VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
476
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Patient Education
HUMAN PAPILLOMAVIRUS VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
477
CLINICAL PEARL
Bioterrorism Providers need to have a basic understanding of vaccines available against possible biological weapons. The CDC Web site has an area dedicated to bioterrorism located at www.bt.cdc.gov/bioterrorism/. There are vaccines available for anthrax and smallpox, although this chapter does not discuss them because they are not currently recommended. Full prescribing information for both the anthrax and the smallpox vaccines are available at the CDC National Immunization Web site at www.cdc.gov/ nip/publications/acip-list.htm.
Monitoring
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
INFLUENZA VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
478
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
PNEUMOCOCCAL VACCINE
Pharmacodynamics
479
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Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
480
3827_Ch19_447_496 02/07/15 12:05 PM Page 480
Monitoring
Patient Education
MENINGOCOCCAL VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
481
3827_Ch19_447_496 02/07/15 12:05 PM Page 481
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
LYME DISEASE VACCINE
Pharmacodynamics
482
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TYPHOID VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
CHOLERA VACCINE
Pharmacodynamics
JAPANESE ENCEPHALITIS VIRUS VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
483
3827_Ch19_447_496 02/07/15 12:05 PM Page 483
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
PLAGUE VACCINE
Pharmacodynamics
RABIES VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
484
3827_Ch19_447_496 02/07/15 12:05 PM Page 484
Clinical Use and Dosing
Monitoring
Patient Education
485
Table 19–6 Issues in Immunization
Childhood Immunization
Standards for Child and Adolescent Immunization Practices (National Vaccine Advisory Committee, 2009) AVAILABILITY OF VACCINES
ASSESSMENT OF VACCINATION STATUS
EFFECTIVE COMMUNICATION ABOUT VACCINE BENEFITS AND RISKS
PROPER STORAGE AND ADMINISTRATION OF VACCINES AND DOCUMENTATION OF VACCINATIONS
IMPLEMENTATION OF STRATEGIES TO IMPROVE VACCINATION COVERAGE
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486
Table 19–6 Issues in Immunization—cont’d
Standards for Adult Immunization Practices (National Vaccine Advisory Committee, 2013) MAKE VACCINATIONS AVAILABLE.
ASSESS PATIENTS’ VACCINATION STANDARDS.
COMMUNICATE EFFECTIVELY WITH PATIENTS.
ADMINISTER AND DOCUMENT VACCINATIONS PROPERLY.
IMPLEMENT STRATEGIES TO IMPROVE VACCINATION RATES.
PARTNER WITH THE COMMUNITY.
Immunization in Special Populations PREGNANT PATIENTS
May Be Given Contraindicated During Vaccine if Indicated Pregnancy Comments
Routine
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487
Table 19–6 Issues in Immunization—cont’d
Travel and Others
Immunocompromised Patients
Travel Immunization
May Be Given Contraindicated Vaccine if Indicated During Pregnancy Comments
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IMMUNE GLOBULIN SERUMS
Pharmacodynamics
Pharmacokinetics
488
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Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
489
Table 19–7 ! Dosage Schedule: Immune Globulins
Drug Indication Dose Comments
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490
Table 19–7 ! Dosage Schedule: Immune Globulins—cont’d
Drug Indication Dose Comments
Monitoring
Patient Education
DIAGNOSTIC BIOLOGICALS TUBERCULIN PURIFIED PROTEIN DERIVATIVE
Pharmacodynamics
Pharmacotherapeutics Precautions and Contraindications
3827_Ch19_447_496 02/07/15 12:05 PM Page 490
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
IMMUNOMODULATORS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
491
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Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
492
Table 19–8 " Drug Interactions: Immunomodulators
Drug Interacting Drug Possible Effect Implications
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493
Table 19–8 " Drug Interactions: Immunomodulators—cont’d
Drug Interacting Drug Possible Effect Implications
Monitoring
Patient Education
REFERENCES
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494
3827_Ch19_447_496 02/07/15 12:05 PM Page 494
495
3827_Ch19_447_496 02/07/15 12:05 PM Page 495
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497
CHAPTER 20
Teri Moser Woo
HISTAMINE2 RECEPTOR ANTAGONISTS, 519 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
PROKINETICS, 524 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
PROTON PUMP INHIBITORS, 528 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
LAXATIVES, 533 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
T ANTACIDS
ANTACIDS, 497 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ANTIDIARRHEALS, 502 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CYTOPROTECTIVE AGENTS, 508 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ANTIEMETICS, 510 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
EMETICS, 519
3827_Ch20_497-540 01/07/15 1:30 PM Page 497
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
498
Table 20–1 ! Pharmacokinetics: Selected Antacids
Drug Acid-Neutralizing Capacity (ANC)Onset Peak Duration Half-Life Elimination
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
499
Table 20–2 " Drug Interactions: Selected Antacids
Drug Interacting Drug Possible Effect Implications
3827_Ch20_497-540 01/07/15 1:30 PM Page 499
500
Table 20–2 " Drug Interactions: Selected Antacids—cont’d
Drug Interacting Drug Possible Effect Implications
Table 20–3 # Dosage Schedule: Selected Antacids
Drug Indication Dosage Form Dosage Schedule
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501
Table 20–3 # Dosage Schedule: Selected Antacids—cont’d
Drug Indication Dosage Form Dosage Schedule
Rational Drug Selection
3827_Ch20_497-540 01/07/15 1:30 PM Page 501
Monitoring
Patient Education
ANTIDIARRHEALS
Pharmacodynamics
502
3827_Ch20_497-540 01/07/15 1:30 PM Page 502
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
503
DurationOnset Peak Half-Life Elimination
Table 20–4 ! Pharmacokinetics: Selected Antidiarrheals
Drug
3827_Ch20_497-540 01/07/15 1:30 PM Page 503
Drug Interactions
Clinical Use and Dosing
Adverse Drug Reactions
504
3827_Ch20_497-540 01/07/15 1:30 PM Page 504
505
Table 20–5 " Drug Interactions: Selected Antidiarrheals
Drug Interacting Drug Possible Effect Implications
CLINICAL PEARL
Oral Rehydration Therapy Evaluation of the effectiveness of oral rehydration is based on at least three wet diapers per 24 hours in in- fants. For children older than 1 year, avoid all fruit juices and other drinks that contain fructose because they usually make the diarrhea worse. If the infant or child is drinking milk or lactose-based formula, try withholding milk or lactose products. Probiotics may decrease the duration of diarrhea. Resolution of the diarrhea suggests lactose intolerance.
3827_Ch20_497-540 01/07/15 1:30 PM Page 505
Rational Drug Selection
506
Table 20–6 # Dosage Schedule: Selected Antidiarrheals
Drug Indication Dosage Form Initial Dose Additional Doses
3827_Ch20_497-540 01/07/15 1:30 PM Page 506
Patient Education
507
Table 20–6 # Dosage Schedule: Selected Antidiarrheals—cont’d
Drug Indication Dosage Form Initial Dose Additional Doses
3827_Ch20_497-540 01/07/15 1:30 PM Page 507
CYTOPROTECTIVE AGENTS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
508
Table 20–7 ! Pharmacokinetics: Cytoprotective Agents
Drug Onset Peak Duration Protein Binding Half-Life Elimination
3827_Ch20_497-540 01/07/15 1:30 PM Page 508
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
509
Table 20–8 " Drug Interactions: Cytoprotective Agents
Drug Interacting Drug Possible Effect Implications
3827_Ch20_497-540 01/07/15 1:30 PM Page 509
Rational Drug Selection
Monitoring
Patient Education
ANTIEMETICS
510
Table 20–9 # Dosage Schedule: Cytoprotective Agents
Drug Indication Dosage Forms Dosage Schedule
3827_Ch20_497-540 01/07/15 1:30 PM Page 510
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
511
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512
Table 20–10 ! Pharmacokinetics: Selected Antiemetics
Drug Onset Peak Duration Protein Binding Half-Life Elimination
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513
Table 20–11 " Drug Interactions: Selected Antiemetics
Drug Interacting Drug Possible Effect Implications
3827_Ch20_497-540 01/07/15 1:30 PM Page 513
514
Table 20–11 " Drug Interactions: Selected Antiemetics—cont’d
Drug Interacting Drug Possible Effect Implications
3827_Ch20_497-540 01/07/15 1:30 PM Page 514
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
515
3827_Ch20_497-540 01/07/15 1:30 PM Page 515
516
Table 20–12 # Dosage Schedule: Selected Antiemetics
Drug Indications Dosage Form Dosage Schedule Notes
3827_Ch20_497-540 01/07/15 1:30 PM Page 516
517
Table 20–12 # Dosage Schedule: Selected Antiemetics—cont’d
Drug Indications Dosage Form Dosage Schedule Notes
3827_Ch20_497-540 01/07/15 1:30 PM Page 517
518
Table 20–12 # Dosage Schedule: Selected Antiemetics—cont’d
Drug Indications Dosage Form Dosage Schedule Notes
! !
!
Monitoring
Patient Education
3827_Ch20_497-540 01/07/15 1:30 PM Page 518
EMETICS
HISTAMINE2 RECEPTOR ANTAGONISTS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
519
3827_Ch20_497-540 01/07/15 1:30 PM Page 519
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
520
Table 20–13 ! Pharmacokinetics: Histamine2 Blockers
Drug Onset Peak Duration Protein Binding Bioavailability Half-Life Metabolized Elimination
3827_Ch20_497-540 01/07/15 1:30 PM Page 520
521
Table 20–14 " Drug Interactions: Histamine2 Blockers
Drug Interacting Drug Possible Effect Implications
3827_Ch20_497-540 01/07/15 1:30 PM Page 521
522
Table 20–15 # Dosage Schedule: Histamine2 Blockers
Drug Indication Dosage Form Initial Dose Maintenance Dose
3827_Ch20_497-540 01/07/15 1:30 PM Page 522
523
Table 20–15 # Dosage Schedule: Histamine2 Blockers—cont’d
Drug Indication Dosage Form Initial Dose Maintenance Dose
3827_Ch20_497-540 01/07/15 1:30 PM Page 523
Rational Drug Selection
Monitoring
Patient Education
PROKINETICS
524
3827_Ch20_497-540 01/07/15 1:30 PM Page 524
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
525
Table 20–16 ! Pharmacokinetics: Prokinetic Agents
Onset Peak Duration Protein Binding Bioavailability Half-Life Elimination
3827_Ch20_497-540 01/07/15 1:30 PM Page 525
Drug Interactions
Clinical Use and Dosing
526
Table 20–17 " Drug Interactions: Prokinetic Agents
Drug Interacting Drug Possible Effect Implications
3827_Ch20_497-540 01/07/15 1:30 PM Page 526
Rational Drug Selection
Monitoring
Patient Education
527
Table 20–18 # Dosage Schedule: Prokinetic Agents
Drug Indication Available Dosage Dosage Schedule Notes
3827_Ch20_497-540 01/07/15 1:30 PM Page 527
PROTON PUMP INHIBITORS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
528
On The Horizon ILAPRAZOLE
Ilaprazole is a proton pump inhibitor developed by Il-Yang Pharmaceutical (Korea) and is approved for use in Korea and China. It has completed phase II trials in the United States.
Onset
Table 20–19 ! Pharmacokinetics: Proton Pump Inhibitors
Drug Peak Duration Protein Binding Bioavailability Half-Life Elimination
3827_Ch20_497-540 01/07/15 1:30 PM Page 528
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
529
3827_Ch20_497-540 01/07/15 1:30 PM Page 529
Drug Interactions
Clinical Use and Dosing
530
Table 20–20 " Drug Interactions: Proton Pump Inhibitors
Drug Interacting Drug Possible Effect Implications
3827_Ch20_497-540 01/07/15 1:30 PM Page 530
531
Table 20–21 # Dosage Schedule: Proton Pump Inhibitors
Drug Indication Dosage Form Initial Dose Maintenance Dose
3827_Ch20_497-540 01/07/15 1:30 PM Page 531
532
Table 20–21 # Dosage Schedule: Proton Pump Inhibitors—cont’d
Drug Indication Dosage Form Initial Dose Maintenance Dose
3827_Ch20_497-540 01/07/15 1:30 PM Page 532
Rational Drug Selection
Monitoring
Patient Education
LAXATIVES
533
3827_Ch20_497-540 01/07/15 1:30 PM Page 533
Pharmacodynamics Stimulants
Osmotics
Bulk-Producing Laxatives
Lubricants
Surfactants
Hyperosmolar Laxatives
Chloride Channel Activators
Opioid-Receptor Antagonists
Pharmacokinetics Absorption and Distribution
534
3827_Ch20_497-540 01/07/15 1:30 PM Page 534
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
535
Table 20–22 ! Pharmacokinetics: Selected Laxatives
Drug Class Onset Peak Site of Action Elimination
3827_Ch20_497-540 01/07/15 1:30 PM Page 535
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
536
3827_Ch20_497-540 01/07/15 1:30 PM Page 536
537
Table 20–23 " Drug Interactions: Selected Laxatives
Drug Interacting Drug Possible Effect Implications
Table 20–24 # Dosage Schedule: Selected Laxatives
Drug Indication Dosage Form Dose Notes
3827_Ch20_497-540 01/07/15 1:30 PM Page 537
538
Table 20–24 # Dosage Schedule: Selected Laxatives—cont’d
Drug Indication Dosage Form Dose Notes
3827_Ch20_497-540 01/07/15 1:30 PM Page 538
REFERENCES
539
CLINICAL PEARL
Polyethylene Glycol/Electrolyte Solution The taste of polyethylene glycol/electrolyte solution is quite salty, and many patients find it difficult to con- sume the required volume in the required amount of time. Place the container of solution in ice in a basin. Do not pour it over ice, which will melt and increase the volume the patient must consume. Have the patient drink 240 mL of fluid each 10 minutes and give a Tic-Tac or similar small mint-flavored hard candy to suck on between glasses of the drug. This reduces the salty taste in the mouth and makes the drug more palatable.
Monitoring
Patient Education
3827_Ch20_497-540 01/07/15 1:30 PM Page 539
540
3827_Ch20_497-540 01/07/15 1:30 PM Page 540
541
CHAPTER 21
Marylou Robinson • Kathy Shaw
BISPHOSPHONATES, 542 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
HYPOTHALAMIC AND PITUITARY HORMONES, 549 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
EXOCRINE PANCREATIC ENZYMES, 553 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ENDOCRINE PANCREATIC HORMONES INSULIN, 557 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ORAL DIABETIC AGENTS, 567
BIGUANIDES, 567 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
SULFONYLUREAS, 573 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ALPHAGLUCOSIDASE INHIBITORS, 578 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
THIAZOLIDINEDIONES , 580 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
MEGLITINIDES, 583 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
DIPEPTIDYL PEPTIDASE4 INHIBITORS , 586 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
SELECTIVE SODIUM GLUCOSE COTRANSPORTER 2 SGLT2 INHIBITORS, 589 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
AMYLIN AGONISTS, 592 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
GLUCAGONLIKE PEPTIDE AGONISTS, 595 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
GLUCAGON, 598 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
3827_Ch21_541-614 01/07/15 5:40 PM Page 541
BISPHOSPHONATES
Pharmacodynamics
542
THYROID AGENTS, 599 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ANTITHYROID AGENTS, 605 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
AROMATASE INHIBITORS, 609 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
3827_Ch21_541-614 01/07/15 5:40 PM Page 542
Pharmacokinetics Absorption and Distribution
543
Bone is damaged by trauma or aging process.
Osteoclasts adhere to damaged surface and secrete
acids and enzymes.
Bone is dissolved, leaving resorption pit.
Osteoblasts adhere to resorption pit and build new bone.
Osteoclasts leave area.
Figure 21–1. Bone remodeling. Damaged bone sections are re- moved by osteoclasts that use pseudopods to attach to bone surface. Bone is dissolved, leaving a resorption pit. The osteoclasts then leave the site of damage. Osteoblasts enter the resorption pit and build new bone. The process takes 4 to 5 months.
3827_Ch21_541-614 01/07/15 5:40 PM Page 543
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
544
Table 21–1 ! Pharmacokinetics: Bisphosphonates
Bioavailability Steady-State Half-Life Onset of (With/Without Vd Exclusive Normal Renal
Drug Effect Peak Duration Food) of Bone (Function) Elimination
3827_Ch21_541-614 01/07/15 5:40 PM Page 544
Drug Interactions Clinical Use and Dosing
545
Table 21–2 " Drug and Food Interactions: Bisphosphonates
Drug Interacting Drugs and Food Possible Effect Implications
3827_Ch21_541-614 01/07/15 5:40 PM Page 545
546
Table 21–3 # Dosage Schedule: Selected Bisphosphonates
Drug Indication Dosage Forms Initial Dose Maintenance Dose
3827_Ch21_541-614 01/07/15 5:40 PM Page 546
547
Table 21–3 # Dosage Schedule: Selected Bisphosphonates—cont’d
Drug Indication Dosage Forms Initial Dose Maintenance Dose
3827_Ch21_541-614 01/07/15 5:40 PM Page 547
Rational Drug Selection
Monitoring
Patient Education
548
3827_Ch21_541-614 01/07/15 5:40 PM Page 548
HYPOTHALAMIC AND PITUITARY HORMONES
Pharmacodynamics
549
HypothalamusStimulation
Secretes growth hormone– releasing hormone
Anterior pituitary
Secretes growth hormone
Decreased glucose
Increased glucose
Inhibition
Increased protein synthesis Increased lipolysis
Increased cell growth Retention of sodium, potassium, phosphorus
Figure 21–2. Hypothalamus-pituitary–growth hormone axis.
3827_Ch21_541-614 01/07/15 5:40 PM Page 549
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
550
Table 21–4 ! Pharmacokinetics: Growth Hormones
Onset of Peak Duration Half-Life (Normal Drug Effect (Drug in Plasma) (Drugin Plasma) Bioavailability Renal Function) Elimination
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551
Table 21–5 # Dosage Schedule: Selected Growth Hormones
Drug* Indication Dosage Form Initial Dose Maintenance Dose
3827_Ch21_541-614 01/07/15 5:40 PM Page 551
Rational Drug Selection
Monitoring
Patient Education
552
Table 21–5 # Dosage Schedule: Selected Growth Hormones—cont’d
Drug* Indication Dosage Form Initial Dose Maintenance Dose
The average expected growth with hormone therapy can be estimated. For girls, subtract 13 cm from the father’s height and average this number with the mother’s height. For boys, add 13 cm to the mother’s height and average the sum with the father’s height (Albert, 2012). Conversion from inches to cm is achieved by using the formula 1 in. = 2.54 cm. A mother who is 65 in. tall would be 165.1 cm. A father who is 68 in. tall would be 172.72 cm. For their daughter, the calculation would be 172.72 – 13 cm, or 159.72, which averaged with the mother’s 165.1 cm would yield a 162.41 cm expected height.
BOX 21–1 CALCULATING TARGET HEIGHT GOAL
3827_Ch21_541-614 01/07/15 5:40 PM Page 552
EXOCRINE PANCREATIC ENZYMES
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
553
On The Horizon GROWTH HORMONE
There are multiple studies currently in progress studying the short- and long-term effects of growth horomone in children and adults. Sustained, related, once-weekly injections of growth hormone currently in clinical trials portend sustained growth without impaired bone maturation.
3827_Ch21_541-614 01/07/15 5:41 PM Page 553
Adverse Drug Reactions
Drug and Food Interactions
Clinical Use and Dosing
554
Table 21–6 " Drug and Food Interactions: Pancreatic Enzymes
Drug Interacting Drug Possible Effect Implications
Table 21–7 # Dosage Schedule: Pancreatic Enzymes
Drug Indication Dosage in USP Units Initial Dose Maintenance Dose
3827_Ch21_541-614 01/07/15 5:41 PM Page 554
Rational Drug Selection
555
Table 21–7 # Dosage Schedule: Pancreatic Enzymes—cont’d
Drug Indication Dosage in USP Units Initial Dose Maintenance Dose
3827_Ch21_541-614 01/07/15 5:41 PM Page 555
Monitoring
Patient Education
ENDOCRINE PANCREATIC HORMONES (INSULIN)
556
3827_Ch21_541-614 01/07/15 5:41 PM Page 556
Pharmacodynamics
Action on Glucose Transporters
Action on the Liver
Action on Muscle Cells
Action on Adipose Tissue
Pharmacokinetics Absorption and Distribution
557
3827_Ch21_541-614 01/07/15 5:41 PM Page 557
558
Increased serum glucose levels
Increased ATP production
Potassium channels close
Depolarization of the pancreatic beta cell
Voltage-gated calcium channels open
Increased intracellular calcium
Increased insulin secretion
Insulin attaches to insulin receptor on body cells
Opens channels in plasma membrane
Potassium enters cell
Pancreatic beta cell repolarizes
Voltage-gated calcium channels close
Decreased intracellular calcium
Decreased insulin secretion
Glycogen
Lipids
Pyruvate
Glucose enters cell
Mg2+ and PO3 enter cell
Amino acids enter cell
Generation of insulin substrate (IRS-1) by autophosphorylation
CO2
Opens Glut-4 transport protein channel
Protein synthesis
Figure 21–3. Mechanism of insulin release from beta cells.
3827_Ch21_541-614 01/07/15 5:41 PM Page 558
559
Table 21–8 ! Pharmacokinetics: Insulins
Onset (m) Peak (h) Duration (h)* Elimination Compatibility
Short-Acting
Intermediate-Acting
Long-Acting
Inhaled
On The Horizon INSULIN DEGLUDEC
The ultra–long-acting basal insulin analogue degludec (Tresiba) has been placed on a more extended roll-out by Novo-Nordisk in the United States. It is used for both type 1 and type 2 patients, especially those who need to overcome nocturnal hypoglycemia. The 42 hour action time may allow a staggered administration plan. Due to limited post-marketing experience, it is not fully described in this edition.
3827_Ch21_541-614 01/07/15 5:41 PM Page 559
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
560
On The Horizon PIPELINE DRUGS
There are many drugs currently in the pipeline to treat DM. Insulin degludec (Tresiba) has a longer duration of action than insulin glargine. Insulin degludec/liraglutide (Xultopy) is an insulin/GLP-1 agonist combination in phase 3 trials. Other dia- betes drugs in phase III trials include exenatice subcutaneous implant (ITCA 650, Intarcia Therapeutics); semaglutide (Novo Nordisk) is a once-weekly GLP-1 analog; omariglipin (Merck) is a once-weekly DPP-4 inhibitor similar to once daily Januvia; Oral-Lyn (Generex) is an investigational liquid regular recom- binant human insulin that is delivered to the buccal mucosa using a trademarked RapidMist device; and insulin peglispro (Eli Lilly) is a new long-acting basal insulin.
Lixisenatide (Lyxumia), a once-daily prandial GLP-1 recep- tor agonist approved in Europe, was denied FDA approval in June 2014 due to pronounced after meal hypoglycemia.
3827_Ch21_541-614 01/07/15 5:41 PM Page 560
Drug Interactions
Clinical Use and Dosing
561
Table 21–9 " Drug Interactions With Insulin
Interacting Drug Possible Effects Implications
3827_Ch21_541-614 01/07/15 5:41 PM Page 561
562
Table 21–10 # Dosage Schedule: Insulin
Drug Dosage Form Schedule Initial Dose Comments
3827_Ch21_541-614 01/07/15 5:41 PM Page 562
563
Table 21–10 # Dosage Schedule: Insulin—cont’d
Drug Dosage Form Schedule Initial Dose Comments
3827_Ch21_541-614 01/07/15 5:41 PM Page 563
Rational Drug Selection
564
CLINICAL PEARL
For patients on insulin pumps, be attentive to daylight saving time changes. Many pump computers are not GPS enabled or time zone adjusting. This is not an issue with basal insulin provision, but could be significant for rapid-acting forms. Verify date and time settings during appointments (Aldasouqui & Reed, 2014).
3827_Ch21_541-614 01/07/15 5:41 PM Page 564
Monitoring
565
3827_Ch21_541-614 01/07/15 5:41 PM Page 565
Patient Education
566
3827_Ch21_541-614 01/07/15 5:41 PM Page 566
ORAL AGENTS
BIGUANIDES
Pharmacodynamics
567
3827_Ch21_541-614 01/07/15 5:41 PM Page 567
Pharmacokinetics Absorption and Distribution
568
Table 21–11 ! Pharmacokinetics: Selected Antihyperglycemic Agents
Protein Drug Onset* Peak* Duration* Binding Bioavailability Half-Life Excretion
3827_Ch21_541-614 01/07/15 5:41 PM Page 568
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
569
Table 21–11 ! Pharmacokinetics: Selected Antihyperglycemic Agents—cont’d
Protein Drug Onset* Peak* Duration* Binding Bioavailability Half-Life Excretion
3827_Ch21_541-614 01/07/15 5:41 PM Page 569
Adverse Drug Reactions
Drug Interactions
570
Table 21–12 " Drug Interactions With Metformin
Interacting Drug Possible Effects Implications
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Clinical Use and Dosing
571
Table 21–13 # Dosage Schedule: Selected Metformin Formulations
Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose
Extended-Release
Combination Drugs
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572
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Monitoring
SULFONYLUREAS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
573
CLINICAL PEARL
When metformin is added to a sulfonylurea, the increased sensitivity to insulin caused by metformin results in less need for the insulin secretion generated by the sulfonylurea. If the BG level drops too much, the dose of the sulfonylurea should be reduced.
Patient Education
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574
Table 21–14 ! Pharmacokinetics: Sulfonylureas
Protein Drug Onset (h) Peak (h) Duration (h) Binding Half-Life (h) Metabolism Elimination
First-Generation
Second-Generation
Metabolism and Excretion
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Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
575
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Clinical Use and Dosing
576
Table 21–15 " Drug Interactions: Sulfonylureas
Drug Interacting Drug Possible Effect Implications
Table 21–16 # Dosage Schedule: Sulfonylureas
Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose
First-Generation
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Rational Drug Selection
Monitoring
Patient Education
577
Table 21–16 # Dosage Schedule: Sulfonylureas—cont’d
Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose
Second-Generation
Glyburide
CLINICAL PEARL
Tolazamide has the added advantage that it may be crushed and put down a nasogastric tube or sprinkled on applesauce or other soft food for patients who have difficulty in swallowing tablets.
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ALPHA-GLUCOSIDASE INHIBITORS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
578
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
579
CLINICAL PEARL
Starting the alpha-glucosidase inhibitor at 25 mg daily for 1 week and increasing the dose to 25 mg twice daily for 1 week and then to 25 mg 3 times daily for 1 week decreases the incidence of GI-adverse responses.
Table 21–17 " Drug Interactions: Alpha-Glucosidase Inhibitors
Drug Interacting Drug Possible Effect Implications
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Rational Drug Selection
Monitoring
Patient Education
580
CLINICAL PEARL
The delayed absorption of carbohydrates caused by alpha-glucosidase inhibitors results in less need for the insulin secretion generated by a sulfonylurea. If the BG level drops too much, the dose of the sulfonyl - urea should be reduced.
Table 21–18 # Dosage Schedule: Alpha-Glucosidase Inhibitors
Drug Dosage Form Initial Dose Maintenance Dose Maximum Dose
THIAZOLIDINEDIONES
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Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
581
CLINICAL PEARL
When thiazolidinediones are added to a sulfonylurea in a diabetic regimen, the increased sensitivity to insulin caused by the thiazolidinedione results in less need for the insulin secretion generated by the sulfonyl - urea. If the BG level drops too much, the dose of the sulfonylurea should be reduced.
Pharmacotherapeutics Precautions and Contraindications
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
582
Table 21–19 " Drug Interactions With Thiazolidinediones
Drug Interacting Drug Possible Effect Implications
Table 21–20 # Dosage Schedule: Thiazolidinediones
Drug Initial Dose Dosage Form Maximum Dose Maintenance Dose
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Monitoring
Patient Education
MEGLITINIDES
583
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Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
584
Table 21–21 " Drug Interactions With Meglitinides and Repaglinide
Interacting Drug Possible Effect Implications
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Clinical Use and Dosing
Monitoring
Patient Education
585
Table 21–22 # Dosage Schedule: Meglitinides
Drug Initial Dose Dosage Form Maximum Dose Maintenance Dose
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DIPEPTIDYL PEPTIDASE-4 INHIBITORS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
586
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Drug Interactions
Clinical Use and Dosing
587
Table 21–23 " Drug Interactions With Dipeptidyl Peptidase-4 Inhibitors (Gliptins)
Drug Interacting Drug Possible Outcomes Implications
Table 21–24 # Dosage Schedule for Dipeptidyl Peptidase-4 Inhibitors (Gliptins)
Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose
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Rational Drug Selection
588
Table 21–24 # Dosage Schedule for Dipeptidyl Peptidase-4 Inhibitors (Gliptins)—cont’d
Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose
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Monitoring
Patient Education
SELECTIVE SODIUM GLUCOSE CO-TRANSPORTER 2 (SGLT-2) INHIBITORS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
589
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Adverse Drug Reactions
Drug Interactions
590
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Clinical Use and Dosing
Monitoring
591
Table 21–25 " Drug Interactions With SGLT-2 Drugs
Drug Interacting Drug Possible Outcomes Implications
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Patient Education
AMYLIN AGONISTS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
592
Table 21–26 # Dosing Schedule for SGLT2 Drugs
Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose
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Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
593
Table 21–27 " Drug Interactions With GLP-1 and Amylin Agonists
Drug Interacting Drug Possible Outcomes Implications
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Clinical Use and Dosing
Monitoring
Patient Education
594
Table 21–27 " Drug Interactions With GLP-1 and Amylin Agonists—cont’d
Drug Interacting Drug Possible Outcomes Implications
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GLUCAGON-LIKE PEPTIDE AGONISTS
595
Table 21–28 # Dosage Schedule GLP-1 and Amylin Agonists
Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose
Pramlintide Dose in Micrograms
Amount to Draw Up in a U-100 Insulin Syringe
15 30 45 60
120
2.5 5
7.5 10 20
Figure 21–4. Conversion of mcg to units for injecting pramlintide.
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Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
596
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Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
597
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GLUCAGON
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
598
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Monitoring
Patient Education
THYROID AGENTS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
599
Table 21–29 # Dosage Schedule: Glucagon
Drug Initial Dose Dosage Form Maximum Dose
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600
HypothalamusStimulation
Secretes TRHCold, stress, decreased thyroxine
Iodine
Inhibition
Anterior pituitary
Secretes TSH
Thyroid gland
Excess thyroxine
Synthesizes and secretes tri-iodothyronine and thyroxine
Increases: —Metabolic rate in tissues —Oxygen consumption —Body temperature —Heart rate —Respiratory rate —Blood volume —Rate of fat metabolism —Rate of protein metabolism —Rate of carbohydrate metabolism —Enzyme system activity —Growth, differentiation, and maturation of tissues Figure 21–5. Hypothalamus-
pituitary-thyroid hormone axis.
Table 21–30 ! Pharmacokinetics: Oral Thyroid Hormones
Drug Onset* Peak* Duration* Biological Potency Half-Life Excretion
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Adverse Drug Reactions
Drug Interactions Clinical Use and Dosing
601
Table 21–31 " Drug Interactions With Thyroid Hormones
Interacting Drug Possible Outcomes Implications
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602
Table 21–32 # Dosage Schedule: Thyroid Hormones
Drug Indication Dose Form Initial Dose Maintenance Dose
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603
Table 21–32 # Dosage Schedule: Thyroid Hormones—cont’d
Drug Indication Dosage Form Maintenance Dose Initial Dose
CLINICAL PEARL
Thyroid Hormone Replacement During Pregnancy Increasing the dose by 25% usually results in adequate coverage during pregnancy. Recheck TSH levels in 4 weeks to determine any dosage adjustment.
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Inappropriate Use of Thyroid Hormones
604
CLINICAL PEARL
Levothyroxine tablets can be crushed and suspended in a small amount of formula or water for infants who cannot swallow whole tablets. For children who cannot swallow the intact tablet, it may be crushed and sprin- kled over a small amount of food such as cooked cereal or applesauce. The suspension cannot be stored for any period of time. The tablet should be crushed, mixed to form a suspension, and given immediately.
Rational Drug Selection
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Monitoring
Patient Education
ANTITHYROID AGENTS
605
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Pharmacodynamics
Pharmacokinetics Absorption and Distribution
606
Table 21–33 ! Pharmacokinetics: Antithyroid Drugs
Placental Transport and
Protein Breast Milk Drug Onset* Peak* Duration* Bioavailability Binding Levels Half-Life Excretion
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Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
607
Table 21–34 " Drug Interactions With Antithyroid Drugs
Drug Interacting Drug Possible Effect Implications
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Clinical Use and Dosing
Rational Drug Selection
Monitoring
608
Table 21–35 # Dosage Schedule of Antithyroid Drugs
Drug Indication Dosage Form Initial Dose Maintenance Dose
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Patient Education
AROMATASE INHIBITORS
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
609
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Adverse Drug Reactions
Drug Interactions
Education and Lifestyle Management
610
Table 21–36 ! Pharmacokinetics of Aromatase Inhibitors
Drug Site of Metabolism Peak Protein Binding Half-Life (in hours) Elimination
Table 21–37 # Dosing and Indications Aromatase Inhibitors
Drug Indication Dosage Form Initial Dose Maintenance Dose
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REFERENCES
611
Table 21–38 " Drug interactions of Aromatase Inhibitors
Drug Interacting Drug Possible Effect Implications
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612
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613
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615
CHAPTER 22
Diana L Dewel
ANDROGENS AND ANTIANDROGENS, 615 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ESTROGENS AND ANTIESTROGENS, 623 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
PROGESTERONES AND PROGESTERONE ANTAGONISTS, 635 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
OTHER DRUGS AFFECTING THE REPRODUCTIVE SYSTEM, 642 Drugs Commonly Used in Fertility Clinics
Lactation Inhibitors
Drugs Used in Erectile Dysfunction
T
ANDROGENS AND ANTIANDROGENS
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616
BOX 22–1 COMPOUNDS WITH ANTIANDROGENIC PROPERTIES
The problems of reduced potency in the oral form and the virilizing side effects of androgens led investigators to develop drugs that inhibit synthesis and block sex hormone production receptors. This approach of countering the effects of undesir- able androgen excess has enabled therapy at higher dosages. Dihydrotestosterone is the essential androgen in the prostate. The effect of androgens can be reduced by inhibiting 5-alpha-reductase in its target tissues. PSA levels and digital prostate examination are required monitoring for men on these agents. Users of alpha1-adrenergic antagonists may experience hypotension, syncopy, impotence, and decreased libido. Caution is advised with concurrent use of agents that potentiate the alpha1-adrenergic blocking and agents that increase the risk of hypotension.
Finasteride (Propecia, Proscar)
Finasteride, a steroid-like drug, inhibits 5-alpha-reductase, an intracellular enzyme that converts testosterone to 5-alpha- dihydrotestosterone (DHT). It has a 100-fold selectivity for 5-alpha-reductase type 2, the isoenzyme found primarily in the prostate, seminal vesicles, epididymides, and hair follicles. It is well absorbed orally, and the reduction in DHT begins within 8 hours of administration and lasts for about 24 hours. Finasteride undergoes extensive hepatic metabolism, with 39% being excreted in the urine and 57% in feces.
Approximately 90% is bound to plasma proteins. The FDA approved doses of 5 mg per day to treat benign prostatic hyperplasia (BPH). Although early improvement may be seen, 6 to 12 months of therapy may be needed to determine if a beneficial response has been achieved. Most patients experience a rapid regression in prostate gland size, and about 50% experience an increase in urinary flow and improvement in BPH symptoms (Drug Facts and Comparisons, 2005). In 1998, the FDA approved a 1 mg dose for treating male pattern baldness. Three months of therapy are usually required to demonstrate benefits. Stopping the drugs reverses the effect within 12 months. The main undesirable adverse effects are decreased libido and impotence, which occur with both doses.
Dutasteride (Avodart)
Like finasteride, dutasteride inhibits 5-alpha-reductase, an intracellular enzyme that converts testosterone to 5-alpha- dihydrotesterone (DHT). It inhibits both type 1 and type 2 forms of the isoenzyme. It does not bind to the human androgen receptor. It is absorbed well after oral administration and reaches peak serum concentration within 2 to 3 hours. However, peak clinical effect does not occur until 6 to 12 months of therapy have been completed. Heavily bound to plasma protein (99%), it is extensively metabolized by the liver, utilizing the CYP450 3A4/5 substrate. The drug and its metabolites are ex- creted mainly in feces (45%). Only trace amounts are found in the urine. This drug is approved for the treatment of BPH. BPH patients treated with this drug had a decrease of 94% of DHT after 1 year. Because of its long half-life, serum concentrations remain detectable for up to 6 months after discontinuance of treatment. Dutasteride is absorbed through the skin, so women who are pregnant or may become pregnant should not handle dutasteride capsules due to the potential risk of fetal anomaly to a male fetus. The main undesirable adverse effects are decreased libido and impotence.
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617
BOX 22–1 COMPOUNDS WITH ANTIANDROGENIC PROPERTIES—cont’d
Leuprolide Acetate (Lupron)
Leuprolide is a luteinizing hormone–releasing agonist. This drug produces gonadal suppression when blood levels are continuous in the treatment of prostate cancer. It may be given in a dose of 1 mg SC daily or IM every 3 months in the depot formulation. Mean plasma levels are achieved in 4 hours and are maintained after an initial drop in concentration. It has even greater suppression when used with flutamide. In pediatric patients, its use is to treat central precocious puberty. In gynecol- ogy, its use is in reducing uterine fibroids, endometriosis, and polycystic ovary syndrome. Approximately 90% of women with unstaged endometriosis have relief of pain, and 50% regain fertility with leuprolide.
Flutamide (Eulexin, Euflex)
Flutamide behaves like a competitive antagonist at the androgen receptor site, although it is truly a nonsteroidal agent. It has been used with leuprolide for the treatment of advanced prostate cancer and with female androgen excess syndrome. The adverse effects in men are gynecomastia and reversible liver toxicity. Flutamide is rapidly absorbed orally. It is metabo- lized into six compounds and bound 97% to plasma proteins, reaching a steady state by the fourth dose. Flutamide is excreted in the urine but has not required changes in dose unless renal function is less than 29 mL/min. There is a Black-Box Warning regarding hepatic failure, hepatic encephalopathy, and death with this agent. Most of these events have occurred within the first 3 months of therapy. Baseline and monthly liver function testing is necessary for the first 4 months of therapy and then periodically. Medication should be discontinued if any symptoms of hepatic injury or jaundice develop.
Spironolactone (Aldactone)
Spironolactone is another competitive inhibitor of the dihydrotestosterone, aldosterone, and interferes with the androgen receptors in the prostate. It also reduces 17-alpha-hydroxylase activity, lowering plasma levels of testosterone and androstenedione. Refer to Chapter 16 for its uses as a diuretic. Spironolactone is absorbed orally, reaches peak levels in 2 hours, and is metabolized by the liver and excreted through the portal system. Spironolactone has short-term use for primary hyperaldosteronism in patients preoperatively. It is used long-term for those patients who are not good candidates for surgery or those with idiopathic hyperaldosteronism. There are also edematous conditions that require potassium conser- vation, such as congestive heart failure and cirrhosis of the liver associated with ascites. An off-labeled use is in females with androgen excess for the treatment of hirsutism and acne in dosages of 50 to 200 mg/day. Adverse reactions are usually dose- related and reversible when the drug is discontinued. The most common adverse reactions are GI upset, drowsiness, gyneco- mastia, impotence, cutaneous eruptions, and urticaria. Early animal chronic toxicity studies demonstrated tumorigenicity. Therefore, use should be balanced against risk (there is a Black-Box Warning regarding this concern). This drug is contraindi- cated in pregnancy, yet the American Academy of Physicians has stated that it is compatible with breastfeeding. Although this drug is classified as a diuretic, its use in premenstrual syndrome is probably effective because of its antiandrogen effect, even at low doses (25 to 50 mg daily).
Pharmacodynamics
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Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Onset, Peak, and Duration
618
Table 22–1 ! Pharmacokinetics: Androgens and Anti-Androgens
Protein Drug Onset Peak Duration Binding (in %) Half-Life Elimination
Androgens
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Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
619
Table 22–1 ! Pharmacokinetics: Androgens and Anti-Androgens—cont’d
Protein Drug Onset Peak Duration Binding (in %) Half-Life Elimination
Anti-Androgens
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Drug Interactions
Clinical Use and Dosing
620
Table 22–2 " Common Drug Interactions: Androgens and Anti-Androgens
Drug Interacting Drug Possible Effect Implications
Androgens
Anti-Androgens
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Rational Drug Selection
621
Table 22–3 # Dosage Schedule: Androgens and Anti-Androgens
Drug Indication Dosage Form Initial Dose Maintenance Dose
Androgens
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622
Table 22–3 # Dosage Schedule: Androgens and Anti-Androgens—cont’d
Drug Indication Dosage Form Initial Dose Maintenance Dose
Anti-Androgens
Cost
Monitoring
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PATIENT EDUCATION
ESTROGENS AND ANTIESTROGENS
623
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624
BOX 22–2 ANTIESTROGENS
Although naturally occurring hormones such as progesterone and testosterone may modify the action of estrogen, the following discussion focuses on the synthetic estrogen antagonists. Drugs in this class may have limited use by most practitioners in primary care. Clomiphene is used for ovulation stimulation by infertility clinics. Danazol is primarily used for endometriosis by gynecologists, and tamoxifen is used for female cancers by oncologists. Monitoring by primary care providers is essential.
Clomiphene (Clomid)
Clomiphene was the first chemical used to initiate ovulation in normogonadotropic, normoprolactinemic, and anovulatory patients. It has also been used as a component in the management of luteal-phase dysfunction, oligo-ovulation, artificial insemination, unexplained infertility, and in vitro fertilization. Although clomiphene has been used for 30 years, it is still a drug that remains in a specialized practice setting. The list of adverse side effects are hot flashes, multiple gestation, visual symptoms, cervical mucus abnormalities, luteal-phase defect, luteinized unruptured follicle syndrome, ovarian cancer, teratogenicity, enlargement of ovarian cysts, and liver disease.
The agonist–antagonist characteristics of clomiphene depend on the hormone climate. Clomiphene initiates ovulation in the presence of high estrogen levels in anovulatory females. It does this as long as other endogenous mechanisms trigger an LH surge and follicle rupture. Clomiphene blocks endogenous estrogen-negative feedback at the level of the hypothalamus. It also elevates estrogen and progesterone levels higher than normal. Its function may even affect the ovary and pituitary glands. Clomiphene also decreases serum insulin-like growth factors and increases SHBG, which assists those infertile women with polycystic ovary (PCO) disease. It has direct antiestrogenic effects on the endometrium and cervical mucus- producing glands. Elevated estrogen levels of women in the reproductive years can override the direct antiestrogen effects on the endometrium and cervical mucus.
This compound is active when taken orally, but little is known about its metabolism. Half of the compound is excreted in the feces within 5 days of administration. The hypothesis is that it is excreted through a slow enterohepatic pathway.
Danazol (Danocrine)
Although the major use of danazol has been to treat endometriosis, it has been employed in severe fibrocystic breast changes, hematological disorders, and idiopathic thrombocytopenic purpura. Danazol must be used with great caution in hepatic dysfunction and carries a Black-Box Warning for this and for the risk of thromboembolism. The list of adverse effects is long, which is, in part, why this drug is not indicated for most primary care settings.
Danazol suppresses the pituitary-ovarian axis, inhibiting the midcycle surge of LH and FSH to suppress ovarian function. It has weak progestational and androgenic properties, as does its major metabolite, ethisterone. Danazol binds to androgen, progesterone, and glucocorticoid receptors and alters androgen metabolism. It does not inhibit aromatase, the enzyme required for estrogen synthesis. It also increases the clearance rate of progesterone by competing with the hormone for binding proteins. Danazol is taken orally and is slowly metabolized by the liver (CYP450 3A4 inhibitor), being excreted primarily in the urine after a 24 hour half-life.
Tamoxifen (Nolvadex)
Tamoxifen is the first agent in the selective estrogen receptor modulator (SERM) class of medications used to treat conditions that respond to adding or withdrawing estrogens. As the class name implies, these agents target selective estrogen receptors, while not stimulating others. It is used primarily as part of adjuvant therapy for breast cancer in patients with estro- gen receptor (ER)–positive tumors. Recent studies have demonstrated a reduction in breast cancer in those individuals at high risk for developing the disease within 5 years. In the Gail model, age, family history, medical history of premalignant biopsies, and age at first live birth calculate the patient’s absolute risk.
An antiestrogen in mammary tissue, tamoxifen blunts the effect of estrogen and has direct antigrowth activity of its own in the absence of estrogen. The mechanism may be that it blocks estradiol-induced cancer cell growth by altering the local production of growth factors and/or inhibiting the development of the tumor’s blood supply. Tamoxifen con- tinues to stimulate estrogen receptors in the endometrial tissue and causes hyperplasia in the postmenopausal woman’s endometrium and vagina. Several large-scale, longitudinal trials are under way to evaluate its effectiveness in preventing disease in high-risk women. The results will try to address its potential benefits on bone and lipids while reducing the risk on breast tissue.
This is a nonsteroidal agent that is given orally. Peak plasma levels are reached in a few hours with an initial half-life of 7 to 14 hours. The liver extensively metabolizes tamoxifen, and 65% of the drug is excreted through the gut within 2 weeks.
Raloxifene (Evista)
Raloxifene is also a SERM. Indications initially were for osteoporosis prevention in women who cannot or will not take hormone replacement therapy. Post-marketing studies have shown a positive lipid effect, which may improve cardiovascular disease risk. Results from the recent MORE randomized trial demonstrated a 76% reduced risk of invasive breast cancer
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625
BOX 22–2 ANTIESTROGENS—cont’d
among the women taking raloxifene for osteoporosis. This was attributed to the effect of the drug on ER-positive tumors. This drug can be used only in women past menopause who have never had thromboembolic problems.
Raloxifene is a selective estrogen receptor modulator similar to tamoxifen with different degrees of estrogen agonist or antagonist activity in different tissues. It is an estrogen agonist on bone and an antagonist on breast and uterus. Unlike tamoxifen, it appears to be neutral on the vaginal tissues. A comparison of the beneficial effect on bone mineral density is slightly less than that of estrogen. Whether this bone effect will decrease the incidence of fractures has yet to be proved.
Raloxifene is taken orally without regard to meals, with a 60% absorption rate, but is extensively glucuronidated, and only 2% is bioavailable. It is excreted though the GI tract with a half-life of 32.5 hours.
Raloxifene is not indicated for pediatric patients or for premenopausal women. Concomitant hormone replacement ther- apy is not recommended.
The primary reasons sited by patients for discontinuing therapy were hot flashes and leg cramps. One reported that these symptoms may have lasted up to 6 months.
Raloxifene is highly bound (95%) to plasma proteins. Close monitoring or alternative treatments should be considered for patients using bile acid sequestrants, thyroid hormones, and warfarin.
One short-term trial indicated that it might be effective for prevention of postmenopausal bone loss without the risk for breast or uterine cancer. It may also have a beneficial effect on lipid metabolism. More studies are needed to validate that the effect on lipids actually confers a cardio-protective effect. This drug may be useful for advance practice nurses in primary care practices, but at this time, the long-term safety effects are not known. Like estrogens, there is some increase in thromboem- bolic disease, and it is teratogenic.
Patients on concurrent anticoagulant therapy will require frequent INR levels initially during therapy, and dose adjust- ments of anticoagulants may be needed. Women should also be advised to continue with supplemental calcium and vitamin D for bone health.
Raloxifene can be administered orally without regard to food. Patients need to know that hot flashes can sometimes occur at the beginning of therapy, even in postmenopausal women.
The risk of thromboembolic disease (1%) is the same as it is for estrogen users. Individuals on raloxifene should discon- tinue use 72 hours prior to surgery to decrease risk of thrombosis and embolism. When traveling, patients should get up and move around every hour to avoid long periods of inactivity.
Pharmacodynamics
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Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Onset, Peak, and Duration
Pharmacotherapeutics
Precautions and Contraindications
626
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627
Table 22–4 ! Pharmacokinetics: Estrogens and Antiestrogens
Half-Life (in hours by formulation and metabolites in
Site of individuals with Drug Metabolism Active Metabolism normal renal function) Elimination
Estrogens
Antiestrogens
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Adverse Drug Reactions
Drug Interactions
628
Table 22–5 " Common Drug Interactions: Estrogens and Antiestrogens
Drug Interacting Drug Possible Effect Implications
Estrogens
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629
Table 22–5 " Common Drug Interactions: Estrogens and Antiestrogens—cont’d
Drug Interacting Drug Possible Effect Implications
Antiestrogens
Clinical Use and Dosing
3827_Ch22_615-646 01/07/15 5:42 PM Page 629
630
3827_Ch22_615-646 01/07/15 5:42 PM Page 630
Rational Drug Selection
631
3827_Ch22_615-646 01/07/15 5:42 PM Page 631
632
Table 22–6 # Dosage Schedule: Estrogens and Antiestrogens
Drug Indication Dosage Form Initial Dose Maintenance Dose
Estrogens
3827_Ch22_615-646 01/07/15 5:42 PM Page 632
633
Table 22–6 # Dosage Schedule: Estrogens and Antiestrogens—cont’d
Drug Indication Dosage Form Initial Dose Maintenance Dose
Antiestrogens
3827_Ch22_615-646 01/07/15 5:42 PM Page 633
634
Table 22–6 # Dosage Schedule: Estrogens and Antiestrogens—cont’d
Drug Indication Dosage Form Initial Dose Maintenance Dose
3827_Ch22_615-646 01/07/15 5:42 PM Page 634
Monitoring
PATIENT EDUCATION
635
3827_Ch22_615-646 01/07/15 5:42 PM Page 635
PROGESTERONES AND PROGESTERONE ANTAGONISTS
636
Pharmacodynamics
BOX 22–3 PROGESTERONE ANTAGONISTS
Mifepristone (Mifeprex)
Mifepristone was approved by the FDA on September 28, 2000, for termination of intrauterine pregnancy. It has a long half- life (18 h) and may prolong the follicular phase of the subsequent cycle. It is strongly bound to plasma proteins (98%). This binding is saturable and the drug has nonlinear pharmacokinetics with relation to plasma concentration and clearance. The antiprogestational activity results from competitive interaction with progesterone at progesterone receptor sites. The drug inhibits the activity of both endogenous and exogenous progesterone. When there is no progesterone to maintain a preg- nancy, termination results. In 85% of women, mifepristone will act as an abortifacient when used in conjunction with miso- prostol during the first 7 weeks of pregnancy. Women should expect to experience bleeding or spotting for an average of 9 to 16 days. Persistent heavy or moderate bleeding for more than 30 days could indicate an incomplete abortion. There are very specific requirements associated with administration of this drug, and it is best done in clinics that can meet these requirements. The drug is available only from the manufacturer and not through licensed pharmacies.
Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. Off-labeled uses in the treatment of endometriosis, Cushing’s syndrome, and uterine leiomyomata are under study.
3827_Ch22_615-646 01/07/15 5:42 PM Page 636
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Onset, Peak, and Duration
637
Table 22–7 ! Pharmacokinetics: Progesterones and Progesterone Antagonists
Drug Peak Active Metabolite Half-Life Elimination
Progesterones
Progesterone Antagonists
3827_Ch22_615-646 01/07/15 5:42 PM Page 637
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
638
Table 22–8 " Common Drug Interactions: Progesterones and Progesterone Antagonists
Drug Interacting Drug Possible Effect Implications
Progesterones
Progesterone Antagonists
3827_Ch22_615-646 01/07/15 5:42 PM Page 638
639
Table 22–9 # Dosage Schedule: Progesterones and Progesterone Antagonists
Drug Indication Dosage form Initial Dose Maintenance Dose
Progesterones
3827_Ch22_615-646 01/07/15 5:42 PM Page 639
640
Table 22–9 # Dosage Schedule: Progesterones and Progesterone Antagonists—cont’d
Drug Indication Dosage form Initial Dose Maintenance Dose
Progesterone Antagonists
3827_Ch22_615-646 01/07/15 5:42 PM Page 640
641
Table 22–9 # Dosage Schedule: Progesterones and Progesterone Antagonists—cont’d
Drug Indication Dosage form Initial Dose Maintenance Dose
Rational Drug Selection
3827_Ch22_615-646 01/07/15 5:42 PM Page 641
Monitoring
Patient Education
OTHER DRUGS AFFECTING THE REPRODUCTIVE SYSTEM
Drugs Commonly Used in Fertility Clinics Gonadotropin-Releasing Hormone
642
3827_Ch22_615-646 01/07/15 5:42 PM Page 642
Follicle-Stimulating Hormone/Gonadotropins
Luteinizing Hormone and Human Chorionic Gonadotropin
Lactation Inhibitors Bromocriptine
Drugs Used for Erectile Dysfunction Phosphodiesterase Type 5 Inhibitors
643
3827_Ch22_615-646 01/07/15 5:42 PM Page 643
REFERENCES
644
3827_Ch22_615-646 01/07/15 5:42 PM Page 644
645
3827_Ch22_615-646 01/07/15 5:42 PM Page 645
3827_Ch22_615-646 01/07/15 5:42 PM Page 646
647
CHAPTER 23
Cally Bartley
ANTIINFECTIVES, 648 TOPICAL ANTIBACTERIALS, 648 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
ANTIFUNGALS, 651 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
TOPICAL ANTIVIRALS, 658 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
AGENTS USED TO TREAT ACNE, 659 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
TOPICAL CORTICOSTEROIDS, 666 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
TOPICAL IMMUNOMODULATORS, 671 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
TOPICAL ANTIPSORIASIS AGENTS, 672 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
TOPICAL ANTISEBORRHEIC MEDICATIONS, 675 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
TOPICAL ANTIHISTAMINES AND ANTIPRURITICS, 677 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
MOISTURIZERS, EMOLLIENTS, AND LUBRICANTS, 679 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
AGENTS USED IN THE TREATMENT OF BURNS, 680 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
SCABICIDES AND PEDICULICIDES, 681 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
CAUTERIZING AND DESTRUCTIVE AGENTS, 684 Pharmacodynamics Pharmacotherapeutics
KERATOLYTICS, 685 Pharmacodynamics Pharmacotherapeutics
TOPICAL ANESTHETICS, 685 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
MINOXIDIL, 687 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics
MISCELLANEOUS TOPICAL MEDICATIONS, 688 Bath Dermatologicals Astringents Hair-Growth Retardants Sunscreens
3827_Ch23_647-690 02/07/15 11:46 AM Page 647
T
ANTI-INFECTIVES TOPICAL ANTIBACTERIALS
648
Table 23–1 ! Dosage Schedule: Selected Anti-Infectives Used to Treat Skin Disorders
Drug Indication Available Dosage Forms Dosage
Antibacterial
Antifungals
3827_Ch23_647-690 02/07/15 11:46 AM Page 648
649
Table 23–1 ! Dosage Schedule: Selected Anti-Infectives Used to Treat Skin Disorders–cont’d
Drug Indication Available Dosage Forms Dosage
Antivirals
3827_Ch23_647-690 02/07/15 11:46 AM Page 649
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Clinical Use and Dosing
!
650
3827_Ch23_647-690 02/07/15 11:46 AM Page 650
Rational Drug Selection
Monitoring
Patient Education
ANTIFUNGALS
651
3827_Ch23_647-690 02/07/15 11:46 AM Page 651
Pharmacodynamics Topical Antifungals
Systemic Antifungals
652
3827_Ch23_647-690 02/07/15 11:46 AM Page 652
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
653
3827_Ch23_647-690 02/07/15 11:46 AM Page 653
Adverse Drug Reactions
Drug Interactions
654
3827_Ch23_647-690 02/07/15 11:46 AM Page 654
Clinical Use and Dosing
655
3827_Ch23_647-690 02/07/15 11:46 AM Page 655
656
3827_Ch23_647-690 02/07/15 11:46 AM Page 656
Rational Drug Selection
657
Monitoring
Metholated ointment (Vicks VapoRub) is a common lay treatment for onychomycosis. A small study (n = 18) of the use of daily topical mentholated ointment showed a positive treatment effect (83%), with myco- logical cure in 27.8% of study subjects and partial cure in 55.6% (Derby, Rohal, Jackson, Beutler, & Olsen, 2011).
3827_Ch23_647-690 02/07/15 11:46 AM Page 657
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
658
Patient Education
TOPICAL ANTIVIRALS
3827_Ch23_647-690 02/07/15 11:46 AM Page 658
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
AGENTS USED TO TREAT ACNE
Pharmacodynamics Topical Retinoids
659
3827_Ch23_647-690 02/07/15 11:46 AM Page 659
Topical Antibiotics
Systemic Retinoids
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
660
3827_Ch23_647-690 02/07/15 11:46 AM Page 660
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
661
3827_Ch23_647-690 02/07/15 11:46 AM Page 661
Drug Interactions
662
Table 23–2 " Drug Interactions: Selected Acne Medications
Drug Interacting Drug Possible Effect Implications
Topical Acne Medications
Topical Antibiotics
3827_Ch23_647-690 02/07/15 11:46 AM Page 662
Clinical Use and Dosing
663
Table 23–2 " Drug Interactions: Selected Acne Medications—cont’d
Drug Interacting Drug Possible Effect Implications
Systemic Acne Medication
3827_Ch23_647-690 02/07/15 11:46 AM Page 663
664
Table 23–3 ! Dosage Schedule: Selected Acne Medications
Drug Available Dosage Forms Dosage Notes
Retinoids
Topical Antibiotics
Acne Medication
3827_Ch23_647-690 02/07/15 11:46 AM Page 664
Rational Drug Selection
Monitoring
Patient Education
665
3827_Ch23_647-690 02/07/15 11:46 AM Page 665
666
Table 23–4 # Available Dosage Forms: Topical Corticosteroids
Drug Potency Dosage Form Rx Required
Clobetasol
Desonide
Desoximetasone
Fluocinonide
TOPICAL CORTICOSTEROIDS
Pharmacodynamics
3827_Ch23_647-690 02/07/15 11:46 AM Page 666
667
Table 23–4 # Available Dosage Forms: Topical Corticosteroids—cont’d
Drug Potency Dosage Form Rx Required
Fluocinolone Acetonide
Flurandrenolide
Halcinonide
Halobetasol Proprionate
Hydrocortisone
Mometasone Furoate
Triamcinolone Acetonide
Pharmacokinetics Absorption and Distribution
3827_Ch23_647-690 02/07/15 11:46 AM Page 667
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
668
3827_Ch23_647-690 02/07/15 11:46 AM Page 668
669
Table 23–5 ! Dosage Schedule: Selected Topical Corticosteroids
Drug Dosage Comments
Least Potent (group 7)
Mild Potency (group 6)
Lower Mid-Strength Potency (group 5)
Mid-Strength Potency (group 4)
Upper Mid-Strength Potency (group 3)
High Potency (group 2)
Super High Potency (group 1)
3827_Ch23_647-690 02/07/15 11:46 AM Page 669
Rational Drug Selection
Monitoring
Patient Education
670
3827_Ch23_647-690 02/07/15 11:46 AM Page 670
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
671
TOPICAL IMMUNOMODULATORS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
3827_Ch23_647-690 02/07/15 11:46 AM Page 671
Rational Drug Selection
Monitoring
Patient Education
TOPICAL ANTIPSORIASIS AGENTS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
672
3827_Ch23_647-690 02/07/15 11:46 AM Page 672
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
673
3827_Ch23_647-690 02/07/15 11:46 AM Page 673
674
Table 23–6 " Drug Interactions: Selected Psoriasis Medications
Drug Interacting Drug Possible Effect Implications
Table 23–7 ! Dosage Schedule: Topical Psoriasis Medications
Drug Available Dosage Forms Dosage Notes
3827_Ch23_647-690 02/07/15 11:46 AM Page 674
Rational Drug Selection
Monitoring
Patient Education
TOPICAL ANTISEBORRHEIC MEDICATIONS
Pharmacodynamics
675
3827_Ch23_647-690 02/07/15 11:46 AM Page 675
676
Table 23–8 ! Dosage Schedule: Topical Antiseborrheic Medications
Available Drug Indication Dosage Forms Dosage Notes
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
3827_Ch23_647-690 02/07/15 11:46 AM Page 676
Rational Drug Selection
Monitoring
Patient Education
TOPICAL ANTIHISTAMINES AND ANTIPRURITICS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
677
3827_Ch23_647-690 02/07/15 11:46 AM Page 677
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
678
Table 23–9 " Drug Interactions: Topical Antihistamine and Antipruritic Medications
Drug Interacting Drug Possible Effect Implications
Table 23–10 ! Dosage Schedule: Topical Antihistamine and Antipruritic Medications
Available Drug Indication Dosage Form Dosage Comments
3827_Ch23_647-690 02/07/15 11:46 AM Page 678
Monitoring
Patient Education
MOISTURIZERS, EMOLLIENTS, AND LUBRICANTS
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
679
3827_Ch23_647-690 02/07/15 11:46 AM Page 679
AGENTS USED IN THE TREATMENT OF BURNS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Clinical Use and Dosing
Monitoring
Patient Education
680
3827_Ch23_647-690 02/07/15 11:46 AM Page 680
SCABICIDES AND PEDICULICIDES
Pharmacodynamics
681
Table 23–11 ! Dosage Schedule: Ectoparasiticides
Available Drug Indication Dosage Forms Dosage Comments
3827_Ch23_647-690 02/07/15 11:46 AM Page 681
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
682
3827_Ch23_647-690 02/07/15 11:46 AM Page 682
Clinical Use and Dosing
683
3827_Ch23_647-690 02/07/15 11:46 AM Page 683
Rational Drug Selection
Monitoring
Patient Education
CAUTERIZING AND DESTRUCTIVE AGENTS
Pharmacodynamics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Use and Dosing
684
3827_Ch23_647-690 02/07/15 11:46 AM Page 684
KERATOLYTICS
Pharmacodynamics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Clinical Use and Dosing
Patient Education
TOPICAL ANESTHETICS
Pharmacodynamics
685
3827_Ch23_647-690 02/07/15 11:46 AM Page 685
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
686
3827_Ch23_647-690 02/07/15 11:46 AM Page 686
687
Table 23–12 " Drug Interactions: Miscellaneous Topical Medications
Drug Interacting Drug Possible Effect Implications
Table 23–13 ! Dosage Schedule: Miscellaneous Topical Medications
Drug Indication Dosage Comments
Pharmacodynamics MINOXIDIL
3827_Ch23_647-690 02/07/15 11:46 AM Page 687
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
MISCELLANEOUS TOPICAL MEDICATIONS
Bath Dermatologicals
Astringents
688
3827_Ch23_647-690 02/07/15 11:46 AM Page 688
Hair-Growth Retardants
Sunscreens
REFERENCES
689
3827_Ch23_647-690 02/07/15 11:46 AM Page 689
690
3827_Ch23_647-690 02/07/15 11:46 AM Page 690
691
CHAPTER 24
Jennifer Jordan • R. Brigg Turner • Teri Moser Woo
ANTIMICROBIAL RESISTANCE, 692
ANTIBIOTICS: BETALACTAMS, 693
PENICILLINS, 693 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CEPHALOSPORINS, 707 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
FLUOROQUINOLONES, 719 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
LINCOSAMIDES, 726 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
MACROLIDES, AZALIDES, AND KETOLIDES, 729 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
FIDAXOMICIN, 740 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
OXAZOLIDINONES, 741 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
SULFONAMIDES, TRIMETHOPRIM, NITROFURANTOIN, AND FOSFOMYCIN, 744 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
TETRACYCLINES, 751 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
GLYCOPEPTIDES, 757 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ANTIMYCOBACTERIALS, 760 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ANTIVIRALS, 770
NUCLEOSIDE ANALOGUES, 770 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ANTIVIRALS FOR INFLUENZA, 775 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
3827_Ch24_691-800 01/07/15 5:45 PM Page 691
SYSTEMIC AZOLES AND OTHER ANTIFUNGALS, 778 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ANTHELMINTICS, 787 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
METRONIDAZOLE, NITAZOXANIDE, AND TINIDAZOLE, 790 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
692
I
ANTIMICROBIAL RESISTANCE
3827_Ch24_691-800 01/07/15 5:45 PM Page 692
ANTIBIOTICS: BETA-LACTAMS
PENICILLINS
Pharmacodynamics
Penicillin
Aminopenicillins
693
3827_Ch24_691-800 01/07/15 5:45 PM Page 693
Penicillinase-Resistant Penicillins
Anti-Pseudomonal Penicillins
Resistance
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
694
3827_Ch24_691-800 01/07/15 5:45 PM Page 694
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
695
3827_Ch24_691-800 01/07/15 5:45 PM Page 695
696 Ta
b le
2 4–
1 !
P h
ar m
ac o
ki n
et ic
s: P
en ic
ill in
s
D ru
g O
n se
t P
ea k
D u
ra ti
o n
P ro
te in
B
in d
in g
B io
av ai
la b
il it
y H
al f-
Li fe
P en
ic il
li n
as e
R es
is ta
n ce
A ci
d
St ab
il it
y El
im in
at io
n
3827_Ch24_691-800 01/07/15 5:45 PM Page 696
Drug Interactions
Clinical Use and Dosing
697
Table 24–2 " Drug Interactions: Penicillins
Drug Interacting Drug Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 697
698
3827_Ch24_691-800 01/07/15 5:45 PM Page 698
699
3827_Ch24_691-800 01/07/15 5:45 PM Page 699
700
3827_Ch24_691-800 01/07/15 5:45 PM Page 700
Rational Drug Selection
701
Table 24–3 # Dosage Schedule: Penicillins
Maximal Dose and Drug Indications Dosage Forms Initial Dose Maintanence Dose
3827_Ch24_691-800 01/07/15 5:45 PM Page 701
702
Table 24–3 # Dosage Schedule: Penicillins—cont’d
Maximal Dose and Drug Indications Dosage Forms Initial Dose Maintanence Dose
3827_Ch24_691-800 01/07/15 5:45 PM Page 702
703
Table 24–3 # Dosage Schedule: Penicillins—cont’d
Maximal Dose and Drug Indications Dosage Forms Initial Dose Maintanence Dose
3827_Ch24_691-800 01/07/15 5:45 PM Page 703
704
Table 24–3 # Dosage Schedule: Penicillins—cont’d
Maximal Dose and Drug Indications Dosage Forms Initial Dose Maintanence Dose
3827_Ch24_691-800 01/07/15 5:45 PM Page 704
705
Table 24–4 Steps in Antimicrobial Drug Selection
3827_Ch24_691-800 01/07/15 5:45 PM Page 705
Monitoring Patient Education
706
3827_Ch24_691-800 01/07/15 5:45 PM Page 706
CEPHALOSPORINS
Pharmacodynamics Spectrum of Activity
First-Generation Cephalosporins
Second-Generation Cephalosporins and Cephamycins
Third-Generation Cephalosporins
707
3827_Ch24_691-800 01/07/15 5:45 PM Page 707
Fourth-Generation Cephalosporin
Resistance
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Changes Related to Pregnancy and in Children
708
BOX 24–1 ANTI-MRSA CEPHALOSPORINS
Ceftaroline (Teflaro) is an injectable cephalosporin ap- proved for complicated skin and soft tissue infections and CAP. Ceftaroline inhibits cell wall synthesis by bind- ing to the modified PBP sites expressed by MRSA and penicillin-resistant S. pneumoniae. Gram-negative activ- ity is similar to third-generation cephalosporins but does not include Pseudomonas. Ceftobiprole is an in- jectable cephalosporin that has activity against MRSA and pseudomonal species. Ceftobiprole was rejected by the FDA in 2009; however, clinical investigations continue.
3827_Ch24_691-800 01/07/15 5:45 PM Page 708
Pharmacotherapeutics Precautions and Contraindications
709
Table 24–5 ! Pharmacokinetics: Cephalosporins
Drug Onset Peak Bioavailability Half-Life NRF/ESRD*Duration Protein Binding
Elimination (% unchanged in urine)
3827_Ch24_691-800 01/07/15 5:45 PM Page 709
Adverse Drug Reactions
Drug Interactions
710
Table 24–6 " Drug Interactions: Cephalosporins
Drug Interacting Drug Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 710
Clinical Use and Dosing
711
Table 24–7 # Dosage Schedule Cephalosporins
Maximal Dose Drug Indications Dosage Forms Initial Dose and Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 711
712
Table 24–7 # Dosage Schedule Cephalosporins—cont’d
Maximal Dose Drug Indications Dosage Forms Initial Dose and Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 712
713
Table 24–7 # Dosage Schedule Cephalosporins—cont’d
Maximal Dose Drug Indications Dosage Forms Initial Dose and Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 713
714
Table 24–7 # Dosage Schedule Cephalosporins—cont’d
Maximal Dose Drug Indications Dosage Forms Initial Dose and Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 714
715
Table 24–7 # Dosage Schedule Cephalosporins—cont’d
Maximal Dose Drug Indications Dosage Forms Initial Dose and Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 715
716
Table 24–7 # Dosage Schedule Cephalosporins—cont’d
Maximal Dose Drug Indications Dosage Forms Initial Dose and Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 716
Rational Drug Selection
717
On The Horizon CEFTOBIPROLE
Ceftobiprole is a new fifth-generation cephalosporin active against MRSA, DRSP, and Pseudomonas aeruginosa. It is in- tended for use with skin and skin structure infection and for nosocomial pneumonia. It was originally submitted to the FDA in May 2007 for the treatment of complicated skin and skin structure infections. In 2010, the FDA requested further infor- mation and studies before approving ceftobiprole.
3827_Ch24_691-800 01/07/15 5:45 PM Page 717
Monitoring
Patient Education
718
3827_Ch24_691-800 01/07/15 5:45 PM Page 718
FLUOROQUINOLONES
Pharmacodynamics
Spectrum of Activity
Resistance
719
3827_Ch24_691-800 01/07/15 5:45 PM Page 719
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
720
Table 24–8 ! Pharmacokinetics: Fluoroquinolones
Drug Onset Half-Life*Peak Duration Protein Binding Bioavailability Elimination
3827_Ch24_691-800 01/07/15 5:45 PM Page 720
Adverse Drug Reactions
Drug Interactions
721
3827_Ch24_691-800 01/07/15 5:45 PM Page 721
722
Table 24–9 " Drug Interactions: Fluoroquinolones
Drug Interacting Drug Possible Effect Implications
Clinical Use and Dosing
3827_Ch24_691-800 01/07/15 5:45 PM Page 722
723
Table 24–10 # Dosage Schedule: Fluoroquinolones
Drug Indications Dosage Forms Initial Adult Dose Maintanence Dose
3827_Ch24_691-800 01/07/15 5:45 PM Page 723
724
Table 24–10 # Dosage Schedule: Fluoroquinolones—cont’d
Drug Indications Dosage Forms Initial Adult Dose Maintanence Dose
3827_Ch24_691-800 01/07/15 5:45 PM Page 724
Rational Drug Selection
725
3827_Ch24_691-800 01/07/15 5:45 PM Page 725
Monitoring
Patient Education
LINCOSAMIDES
Pharmacodynamics
Spectrum of Activity
726
3827_Ch24_691-800 01/07/15 5:45 PM Page 726
Resistance
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
727
Table 24–11 ! Pharmacokinetics: Lincosamides
Drug Onset Peak Duration Protein Binding Bioavailability Half-Life Elimination
Table 24–12 " Drug Interactions: Lincosamides
Drug Interacting Drug Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 727
Rational Drug Selection
728
Table 24–13 # Dosage Schedule: Lincosamides
Drug Indication Dosage Forms Initial Dose Maintanence Dose
3827_Ch24_691-800 01/07/15 5:45 PM Page 728
Monitoring
Patient Education
MACROLIDES, AZALIDES, AND KETOLIDES
Pharmacodynamics
Spectrum of Activity
729
3827_Ch24_691-800 01/07/15 5:45 PM Page 729
Resistance
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
730
Table 24–14 ! Pharmacokinetics: Macrolides, Azalides, and Ketolides
Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination
3827_Ch24_691-800 01/07/15 5:45 PM Page 730
Adverse Drug Reactions
731
3827_Ch24_691-800 01/07/15 5:45 PM Page 731
Drug Interactions
Clinical Use and Dosing
732
Table 24–15 " Drug Interactions: Macrolides and Azalides
Drug Interacting Drug Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 732
733
Table 24–15 " Drug Interactions: Macrolides and Azalides—cont’d
Drug Interacting Drug Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 733
734
Table 24–16 # Dosage Schedule: Macrolides, Azalides, and Ketolides
Drug Indication Dosage Form Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 734
735
Table 24–16 # Dosage Schedule: Macrolides, Azalides, and Ketolides—cont’d
Drug Indication Dosage Form Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 735
736
Table 24–16 # Dosage Schedule: Macrolides, Azalides, and Ketolides—cont’d
Drug Indication Dosage Form Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 736
737
Table 24–16 # Dosage Schedule: Macrolides, Azalides, and Ketolides—cont’d
Drug Indication Dosage Form Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 737
738
3827_Ch24_691-800 01/07/15 5:45 PM Page 738
Rational Drug Selection
Monitoring
Patient Education
739
3827_Ch24_691-800 01/07/15 5:45 PM Page 739
FIDAXOMICIN
Pharmacodynamics
Spectrum of Activity
Resistance
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
740
3827_Ch24_691-800 01/07/15 5:45 PM Page 740
OXAZOLIDINONES
Pharmacodynamics
Spectrum of Activity
Resistance
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
741
Table 24–17 ! Pharmacokinetics: Oxazolidinones
Drug Onset (h) Peak (h) Duration (h) Protein Binding Bioavailability Half-Life (h) Elimination
3827_Ch24_691-800 01/07/15 5:45 PM Page 741
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
742
Table 24–18 " Drug Interactions: Oxazolidinones
Drug Interacting Drug
FOOD INTERACTIONS
Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 742
Rational Drug Selection
Monitoring
Patient Education
743
Table 24–19 # Dosage Schedules: Oxazolidinones
Drug Indication DoseAvailable Dosage Forms Comments
On The Horizon TEDIZOLID
Tedizolid is a next-generation oxazolidinone in development. It has greater potency than linezolid and a similar antimicrobial spectrum, including but not limited to MRSA, VRE, streptococci, and M. tuberculosis. Clinical trials with up to 21 days of therapy have not demonstrated myelosuppression. Preliminary testing suggests that tedizolid has lower potential than linezolid for MAOI drug and food interactions (Flanagan, Bartizal, Minassian, Fang, & Prokocimer, 2013). Like linezolid, tedizolid has excellent oral bioavailability and tissue penetration (Urbina et al, 2013).
3827_Ch24_691-800 01/07/15 5:45 PM Page 743
SULFONAMIDES, TRIMETHOPRIM, NITROFURANTOIN, AND FOSFOMYCIN
Pharmacodynamics
Sulfonamides
Trimethoprim
Nitrofurantoin
744
3827_Ch24_691-800 01/07/15 5:45 PM Page 744
Fosfomycin
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
745
3827_Ch24_691-800 01/07/15 5:45 PM Page 745
746
Table 24–20 ! Pharmacokinetics: Sulfonamides, Trimethoprim, Nitrofurantoin, and Fosfomycin
Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination
3827_Ch24_691-800 01/07/15 5:45 PM Page 746
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
747
3827_Ch24_691-800 01/07/15 5:45 PM Page 747
Rational Drug Selection
748
Table 24–21 " Drug Interactions: Sulfonamides, Trimethoprim, Nitrofurantoin, and Fosfomycin
Drug Interacting Drug Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 748
749
Table 24–22 # Dosage Schedule: Sulfonamides, Trimethoprim, Nitrofurantoin, and Fosfomycin
Drug Indication Available Dosage Forms Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 749
750
Table 24–22 # Dosage Schedule: Sulfonamides, Trimethoprim, Nitrofurantoin, and Fosfomycin—cont’d
Drug Indication Available Dosage Forms Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 750
Monitoring
Patient Education
Adverse Reactions
TETRACYCLINES
Pharmacodynamics
751
3827_Ch24_691-800 01/07/15 5:45 PM Page 751
Spectrum of Activity
Resistance
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
752
Table 24–23 ! Pharmacokinetics: Tetracyclines
Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination
3827_Ch24_691-800 01/07/15 5:45 PM Page 752
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
753
3827_Ch24_691-800 01/07/15 5:45 PM Page 753
754
Table 24–24 " Drug Interactions: Tetracyclines
Drug Interacting Drug Possible Effects Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 754
Rational Drug Selection
755
Table 24–25 # Dosage Schedule: Tetracyclines
Drug Indication Dosage Form Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 755
756
Table 24–25 # Dosage Schedule: Tetracyclines—cont’d
Drug Indication Dosage Form Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 756
Monitoring
Patient Education GLYCOPEPTIDES
757
3827_Ch24_691-800 01/07/15 5:45 PM Page 757
Pharmacodynamics
Spectrum of Activity
Resistance
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
758
On The Horizon DALBAVANCIN
A new glycopeptide antibiotic, dalbavancin (Zeven), is in phase III trials. The only other drug structurally related to dalbavancin is vancomycin. This once-weekly antibiotic is effective against MRSA and MRSE. In 2008, Pfizer withdrew its global applications to conduct further studies on dalbavancin. In 2010, Pfizer out-licensed dalbavancin to Durata Therapeu- tics, which will continue phase III trials.
3827_Ch24_691-800 01/07/15 5:45 PM Page 758
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
759
3827_Ch24_691-800 01/07/15 5:45 PM Page 759
ANTIMYCOBACTERIALS
Pharmacodynamics Spectrum of Activity
760
3827_Ch24_691-800 01/07/15 5:45 PM Page 760
Resistance
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
761
3827_Ch24_691-800 01/07/15 5:45 PM Page 761
Pharmacotherapeutics Precautions and Contraindications
762
Table 24–26 ! Pharmacokinetics: Selected Antimycobacterials
Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination
3827_Ch24_691-800 01/07/15 5:45 PM Page 762
763
Table 24–27 " Drug Interactions: Selected Antimycobacterials
Drug Interacting Drug Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 763
Adverse Drug Reactions
764
Table 24–27 " Drug Interactions: Selected Antimycobacterials—cont’d
Drug Interacting Drug Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 764
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
765
3827_Ch24_691-800 01/07/15 5:45 PM Page 765
766
Table 24–28 # Dosage Schedule: Selected Antimycobacterials
Drug Indication Dosage Form Initial Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 766
767
Table 24–28 # Dosage Schedule: Selected Antimycobacterials—cont’d
Drug Indication Dosage Form Initial Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 767
768
Table 24–28 # Dosage Schedule: Selected Antimycobacterials—cont’d
Drug Indication Dosage Form Initial Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 768
769
Table 24–28 # Dosage Schedule: Selected Antimycobacterials—cont’d
Drug Indication Dosage Form Initial Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 769
Patient Education
ANTIVIRALS
NUCLEOSIDE ANALOGUES
Pharmacodynamics
770
3827_Ch24_691-800 01/07/15 5:45 PM Page 770
Spectrum of Activity
Resistance
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
771
Table 24–29 ! Pharmacokinetics: Nucleoside Analogues for Herpes Virus Infections
Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination
3827_Ch24_691-800 01/07/15 5:45 PM Page 771
Drug Interactions
Clinical Use and Dosing
772
Table 24–30 " Drug Interactions: Nucleoside Analogues
Drug Interacting Drug Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 772
Rational Drug Selection
773
Table 24–31 # Dosage Schedule: Nucleoside Analogues for Herpes Virus Infections
Drug Indication Dosage Form Initial Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 773
774
Table 24–31 # Dosage Schedule: Nucleoside Analogues for Herpes Virus Infections—cont’d
Drug Indication Dosage Form Initial Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 774
Monitoring
Patient Education
ANTIVIRALS FOR INFLUENZA
775
Table 24–31 # Dosage Schedule: Nucleoside Analogues for Herpes Virus Infections—cont’d
Drug Indication Dosage Form Initial Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 775
Pharmacodynamics Mechanism of Action
Resistance
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
776
CLINICAL PEARL
CDC Influenza Antiviral Recommendations The CDC tracks influenza worldwide to determine circu- lating and emerging strains. Weekly updates on flu activ- ity and surveillance provide information on what strains are circulating in each state. The CDC also provides rec- ommendations for the use of antivirals during influenza season, including updates as resistance patterns emerge. Providers can refer to “Information for Health Profession- als,” accessible at http://www.cdc.gov/flu, for the latest information.
3827_Ch24_691-800 01/07/15 5:45 PM Page 776
Clinical Use and Dosing
777
Table 24–32 ! Pharmacokinetics: Antivirals for Influenza
Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination
Table 24–33 # Dosage Schedule: Antivirals for Influenza
Drug Indications Initial DoseDosage Form Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 777
Rational Drug Selection
Monitoring
Patient Education
SYSTEMIC AZOLES AND OTHER ANTIFUNGALS
Pharmacodynamics
!
778
On The Horizon ISAVUCONAZOLE
Isavaconazole is a novel, broad-spectrum azole intended to treat most yeasts and molds, including fluconazole-resistant Candida strains, Aspergillus, and Zygomyces. It is currently in phase III trials.
3827_Ch24_691-800 01/07/15 5:45 PM Page 778
Spectrum of Activity
Resistance
Pharmacokinetics
Absorption and Distribution
779
Table 24–34 ! Pharmacokinetics: Systemic Antifungal Agents
Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination
3827_Ch24_691-800 01/07/15 5:45 PM Page 779
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
780
3827_Ch24_691-800 01/07/15 5:45 PM Page 780
Adverse Drug Reactions
Drug Interactions
781
Table 24–35 " Drug Interactions: Selected Systemic Antifungal Agents
Drug Interacting Drug Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 781
782
Table 24–35 " Drug Interactions: Selected Systemic Antifungal Agents—cont’d
Drug Interacting Drug Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 782
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
783
Table 24–36 # Dosage Schedule: Selected Systemic Antifungal Agents
Drug Indication Dosage Form Initial and Maintenance Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 783
784
Table 24–36 # Dosage Schedule: Selected Systemic Antifungal Agents—cont’d
Drug Indication Dosage Form Initial and Maintenance Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 784
785
Table 24–36 # Dosage Schedule: Selected Systemic Antifungal Agents—cont’d
Drug Indication Dosage Form Initial and Maintenance Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 785
786
Table 24–36 # Dosage Schedule: Selected Systemic Antifungal Agents—cont’d
Drug Indication Dosage Form Initial and Maintenance Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 786
ANTHELMINTICS
Pharmacodynamics
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
787
3827_Ch24_691-800 01/07/15 5:45 PM Page 787
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
788
Table 24–37 ! Pharmacokinetics: Selected Anthelmintics
Drug Onset Half-LifePeak Protein Binding Bioavailability Elimination
Table 24–38 " Drug Interactions: Selected Anthelmintics
Drug Interacting Drug Possible Effect Implications
3827_Ch24_691-800 01/07/15 5:45 PM Page 788
789
Table 24–39 # Dosage Schedule: Selected Anthelmintics
Drug Indication Initial DoseDosage Form Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 789
Rational Drug Selection
Monitoring
Patient Education
METRONIDAZOLE, NITAZOXANIDE, AND TINIDAZOLE
Pharmacodynamics
790
3827_Ch24_691-800 01/07/15 5:45 PM Page 790
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
791
Table 24–40 ! Pharmacokinetics: Metronidazole, Nitazoxanide, and Tinidazole
Drug Onset (h) Half-LifePeak (h) Duration (h) Protein Binding Bioavailability Elimination
3827_Ch24_691-800 01/07/15 5:45 PM Page 791
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
792
3827_Ch24_691-800 01/07/15 5:45 PM Page 792
793
Table 24–41 # Dosage Schedule: Metronidazole, Nitazoxanide, and Tinidazole
Drug Indication Dosage Form Initial Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 793
794
Table 24–41 # Dosage Schedule: Metronidazole, Nitazoxanide, and Tinidazole—cont’d
Drug Indication Dosage Form Initial Dose Comments
3827_Ch24_691-800 01/07/15 5:45 PM Page 794
Rational Drug Selection
Monitoring
Patient Education
795
3827_Ch24_691-800 01/07/15 5:45 PM Page 795
REFERENCES
796
3827_Ch24_691-800 01/07/15 5:45 PM Page 796
797
3827_Ch24_691-800 01/07/15 5:45 PM Page 797
798
3827_Ch24_691-800 01/07/15 5:45 PM Page 798
799
3827_Ch24_691-800 01/07/15 5:45 PM Page 799
3827_Ch24_691-800 01/07/15 5:45 PM Page 800
801
CHAPTER 25
Teri Moser Woo
ANTIGOUT AND URICOSURIC AGENTS, 801 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CORTICOSTEROIDS, 808 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
NONSTEROIDAL ANTIINFLAMMATORY DRUGS NSAIDS, 816 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ASPIRIN AND NONACETYLATED SALICYLATES, 828 Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
I
ANTIGOUT AND URICOSURIC AGENTS
3827_Ch25_801-836 01/07/15 5:46 PM Page 801
802
Pharmacodynamics Antigout Drugs
Uricosuric Drugs
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
3827_Ch25_801-836 01/07/15 5:46 PM Page 802
Adverse Drug Reactions
803
Table 25–1 ! Pharmacokinetics: Antigout and Uricosuric Agents
Drug Onset Peak (in plasma) Duration Protein Binding Half-Life Elimination
3827_Ch25_801-836 01/07/15 5:46 PM Page 803
Drug Interactions
804
Table 25–2 " Drug Interactions: Antigout and Uricosuric Agents
Drug Interacting Drug Possible Effect Implications
3827_Ch25_801-836 01/07/15 5:46 PM Page 804
805
Table 25–2 " Drug Interactions: Antigout and Uricosuric Agents—cont’d
Drug Interacting Drug Possible Effect Implications
Clinical Use and Dosing
3827_Ch25_801-836 01/07/15 5:47 PM Page 805
806
Table 25–3 # Dosage Schedule: Antigout and Uricosuric Agents
Drug Indication Dosage Form Initial Dose Maintenance Dose
3827_Ch25_801-836 01/07/15 5:47 PM Page 806
Rational Drug Selection
Monitoring
807
3827_Ch25_801-836 01/07/15 5:47 PM Page 807
808
Patient Education
CORTICOSTEROIDS
Pharmacodynamics
3827_Ch25_801-836 01/07/15 5:47 PM Page 808
809
Hypothalamus
Stress Corticotropin-releasing factor (CRF)
Hypoxia Hypoglycemia Hyperthermia
Exercise Cortisol insufficiency
Somatostatin Hypothalamic lesions
Diurnal rhythms
Anterior pituitary
Adrenocorticotropic hormone (ACTH)
Adrenal cortex
Glucocorticoids
• Decreased peripheral uptake of glucose; glucogenesis in liver • Decreased protein synthesis in muscle, lymphoid tissue, skin, bone • Lipolysis in adipose tissue in extremities; lipogenesis in face and trunk • Decreased circulating eosinophils, lymphocytes, monocytes; increased PMNs • Decreased leukocytes at inflammation sites • Decrease in all lymphoid tissues; inhibits production of IL-1 and IL-2 • Blocks generation of fever • Promotes gastric acid secretion; enhances urinary excretion • Decreased proliferation of fibroblasts in connective tissue; delayed healing • Maintains normal contractility of skeletal and cardiac muscle • Increases osteoclastic activity; decreases osteoblastic activity • Maintains normal blood pressure; increases response of arterioles to NE • Modulates emotional and perceptual function; essential for normal arousal
(+)
(+)
(+)
(–)
(–)
(–)
(–)
(–)
Figure 25–1. Hypothalamus- pituitary-adrenal axis and feedback control of cortisol.
3827_Ch25_801-836 01/07/15 5:47 PM Page 809
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
810
Table 25–4 ! Pharmacokinetics: Selected Corticosteroids
Onset Peak Duration Protein Drug (hours) (hours) (days) Binding Half-Life RAP RMP Elimination
3827_Ch25_801-836 01/07/15 5:47 PM Page 810
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
811
3827_Ch25_801-836 01/07/15 5:47 PM Page 811
Drug Interactions
Clinical Use and Dosing
812
3827_Ch25_801-836 01/07/15 5:47 PM Page 812
813
Table 25–5 " Drug Interactions: Selected Corticosteroids
Drug Interacting Drug Possible Effect Implications
3827_Ch25_801-836 01/07/15 5:47 PM Page 813
814
Table 25–6 # Dosage Schedule: Selected Corticosteroids
Drug Indication Dosage Form Dose Notes
3827_Ch25_801-836 01/07/15 5:47 PM Page 814
815
Table 25–6 # Dosage Schedule: Selected Corticosteroids—cont’d
Drug Indication Dosage Form Dose Notes
3827_Ch25_801-836 01/07/15 5:47 PM Page 815
Rational Drug Selection
Monitoring
Patient Education
816
3827_Ch25_801-836 01/07/15 5:47 PM Page 816
NONSTEROIDAL ANTI- INFLAMMATORY DRUGS (NSAIDS)
Pharmacodynamics
817
3827_Ch25_801-836 01/07/15 5:47 PM Page 817
818
Cell membrane destruction
Prostaglandin E Prostacyclin Thromboxane Prostaglandin FInflammation Bronchospasm
CyclooxygenaseLipoxygenase
Vasodilation Edema
Bronchodilation Pain sensitization
Vasodilation Inhibits platelets
Vasoconstriction Platelet aggregation
Vasoconstriction
Arachidonic acid
Leukotrienes Prostaglandins
Figure 25–2. Sequence of events in inflammatory response. The sequence of events is the same, regardless of the source of injury.
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
3827_Ch25_801-836 01/07/15 5:47 PM Page 818
819
Table 25–7 ! Pharmacokinetics: Selected NSAIDs and Acetaminophen
Onset Peak Duration Anal/ Anal/ Anal/ Protein
Drug AntiR AntiR AntiR Binding Bioavailability Half-Life Elimination
3827_Ch25_801-836 01/07/15 5:47 PM Page 819
Pharmacotherapeutics Precautions and Contraindications
820
Table 25–7 ! Pharmacokinetics: Selected NSAIDs and Acetaminophen—cont’d
Onset Peak Duration Anal/ Anal/ Anal/ Protein
Drug AntiR AntiR AntiR Binding Bioavailability Half-Life Elimination
3827_Ch25_801-836 01/07/15 5:47 PM Page 820
Adverse Drug Reactions
Drug Interactions
821
3827_Ch25_801-836 01/07/15 5:47 PM Page 821
822
Table 25–8 " Drug Interactions: Selected NSAIDs and Acetaminophen
Drug Interacting Drug Possible Effect Implications
Clinical Use and Dosing
3827_Ch25_801-836 01/07/15 5:47 PM Page 822
823
Table 25–9 # Dosage Schedule: Selected NSAIDs and Acetaminophen
Drug Indication Dosage Forms Dosage Schedule Comments
ORAL DOSES
SUPPOSITORIES
3827_Ch25_801-836 01/07/15 5:47 PM Page 823
824
Table 25–9 # Dosage Schedule: Selected NSAIDs and Acetaminophen—cont’d
Drug Indication Dosage Forms Dosage Schedule Comments
3827_Ch25_801-836 01/07/15 5:47 PM Page 824
825
Table 25–9 # Dosage Schedule: Selected NSAIDs and Acetaminophen—cont’d
Drug Indication Dosage Forms Dosage Schedule Comments
3827_Ch25_801-836 01/07/15 5:47 PM Page 825
826
Table 25–9 # Dosage Schedule: Selected NSAIDs and Acetaminophen—cont’d
Drug Indication Dosage Forms Dosage Schedule Comments
3827_Ch25_801-836 01/07/15 5:47 PM Page 826
827
3827_Ch25_801-836 01/07/15 5:47 PM Page 827
ASPIRIN AND NONACETYLATED SALICYLATES
Pharmacodynamics
828
Rational Drug Selection
Monitoring
Patient Education
3827_Ch25_801-836 01/07/15 5:47 PM Page 828
829
Table 25–10 ! Pharmacokinetics: Salicylates
Drug Onset Peak Duration Protein Binding Half-Life Elimination
Pharmacokinetics Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics Precautions and Contraindications
3827_Ch25_801-836 01/07/15 5:47 PM Page 829
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
830
3827_Ch25_801-836 01/07/15 5:47 PM Page 830
831
Table 25–11 " Drug Interactions: Salicylates
Drug Interacting Drug Possible Effect Implications
3827_Ch25_801-836 01/07/15 5:47 PM Page 831
832
Table 25–12 # Dosage Schedule: Salicylates
Drug Indication Dosage Forms Dose Comments
3827_Ch25_801-836 01/07/15 5:47 PM Page 832
Rational Drug Selection
Monitoring
833
3827_Ch25_801-836 01/07/15 5:47 PM Page 833
Patient Education
REFERENCES
834
3827_Ch25_801-836 01/07/15 5:47 PM Page 834
835
3827_Ch25_801-836 01/07/15 5:47 PM Page 835
3827_Ch25_801-836 01/07/15 5:47 PM Page 836
837
CHAPTER 26
Teri Moser Woo
DRUGS USED IN TREATING EYE DISORDERS, 837 OPHTHALMIC ANTIINFECTIVES
ANTIGLAUCOMA AGENTS
OCULAR ANTIALLERGIC AND ANTIINFLAMMATORY AGENTS
OCULAR LUBRICANTS
OPHTHALMIC VASOCONSTRICTORS
OPHTHALMIC DIAGNOSTIC PRODUCTS
DRUGS USED IN TREATING EAR DISORDERS, 857 OTIC ANTIINFECTIVES
OTIC ANALGESICS
CERUMINOLYTICS
T
DRUGS USED IN TREATING EYE DISORDERS OPHTHALMIC ANTIINFECTIVES Pharmacodynamics
3827_Ch26_837-862 02/07/15 12:00 PM Page 837
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
838
3827_Ch26_837-862 02/07/15 12:00 PM Page 838
Drug Interactions
839
Table 26–1 ! Drug Interactions: Ophthalmic Anti-Infectives
Drug Interacting Drug Possible Effect Implications
3827_Ch26_837-862 02/07/15 12:00 PM Page 839
Clinical Use and Dosing
840
Table 26–2 Clinical and Laboratory Features of Conjunctivitis
Type Common Patient Group Common Pathogens Clinical Features
3827_Ch26_837-862 02/07/15 12:00 PM Page 840
841
Table 26–3 " Dosage Schedule: Ophthalmic Anti-Infectives
Drug Indication Dosage Form Dose Comments
3827_Ch26_837-862 02/07/15 12:00 PM Page 841
842
Table 26–3 " Dosage Schedule: Ophthalmic Anti-Infectives—cont’d
Drug Indication Dosage Form Dose Comments
3827_Ch26_837-862 02/07/15 12:00 PM Page 842
Rational Drug Selection
Monitoring
Patient Education
843
CLINICAL PEARL
Proper Instillation of Eyedrops
• Wash hands before administering eyedrops. • Tilt head back or lie on back. • Gently pull down lower eyelid to form a “pocket” to
place the drop of medication into. • Squeeze the medication onto the eye without touch-
ing eye with the dropper. • Close eye. Do not rub. Try not to blink. • To prevent cross-contamination, do not use medica-
tion labeled for another patient. • Wait at least 5 minutes between administrations if
administering more than one eye medication.
Proper Instillation of Eye Ointment
• Wash hands prior to administering eye medications. • Warm the ointment by holding it in the hand for 1 to
2 minutes. • With first use of a new tube, squeeze out and discard
the first 0.25 in. of medication. • Angle head back or lie on back. • Gently pull down lower eyelid to form a “pocket” to
place the drop of medication into. • Squeeze 0.25 to 0.5 in. of medication onto the eye
without touching eye with tip of tube. • Close eye for 1 to 2 minutes. Do not rub. • Wipe excess medication from around the eye with a
tissue. • To prevent cross-contamination, do not use medica-
tion labeled for another patient. • Wait at least 10 minutes between administrations if
administering more than one eye medication. • Temporary blurred vision is typical after administration
of ophthalmic ointment.
3827_Ch26_837-862 02/07/15 12:00 PM Page 843
ANTIGLAUCOMA AGENTS
Pharmacodynamics
844
CLINICAL PEARL
Tips for Administering Eye Medications to a Child If only one adult is available to administer eyedrops, then the adult can sit on the floor with the child be- tween his or her legs, with the child’s legs in the same direction as the adult’s. The child’s head can be immo- bilized between the adult’s thighs and the arms held firmly down under the adult’s thighs. This leaves the adult’s hands free to instill the medication. The child may kick, but this will not affect the administration of the medication. Although this method may sound dras- tic, trying to administer eye medication to a squirming toddler or preschooler can be almost impossible, and with this method, the eyedrops can be effectively administered in less than 1 minute.
3827_Ch26_837-862 02/07/15 12:00 PM Page 844
Pharmacokinetics
845
Table 26–4 # Pharmacokinetics: Antiglaucoma Agents
Drug Duration
Beta Blockers
Miotics
Carbonic Anhydrase Inhibitors
Sympathomimetics
Alpha-Adrenergic Agonists
Prostaglandin Analogues
3827_Ch26_837-862 02/07/15 12:00 PM Page 845
Pharmacotherapeutics Precautions and Contraindications
846
3827_Ch26_837-862 02/07/15 12:00 PM Page 846
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
847
3827_Ch26_837-862 02/07/15 12:00 PM Page 847
848
Table 26–5 ! Drug Interactions: Antiglaucoma Agents
Drug Interacting Drug Possible Effect Implications
Beta Blockers
Miotics
Carbonic Anhydrase Inhibitors
3827_Ch26_837-862 02/07/15 12:00 PM Page 848
849
Patient Education
OCULAR ANTIALLERGIC AND ANTIINFLAMMATORY AGENTS
Table 26–5 ! Drug Interactions: Antiglaucoma Agents—cont’d
Drug Interacting Drug Possible Effect Implications
Sympathomimetics
Alpha-Adrenergic Agonists
Prostaglandin Analogues
3827_Ch26_837-862 02/07/15 12:00 PM Page 849
850
Table 26–6 $ Available Dosage Forms: Antiglaucoma Agents
Drug Dosage Form How Supplied
Beta Blockers BETAXOLOL
CARTEOLOL
LEVOBUNOLOL
METIPRANOLOL
TIMOLOL
COMBINATION PRODUCTS
Miotics CARBACHOL
PILOCARPINE
ECHOTHIOPHATE
Carbonic Anhydrase Inhibitors ACETAZOLAMIDE
BRINZOLAMIDE
DORZOLAMIDE
METHAZOLAMIDE
3827_Ch26_837-862 02/07/15 12:00 PM Page 850
851
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Table 26–6 $ Available Dosage Forms: Antiglaucoma Agents—cont’d
Drug Dosage Form How Supplied
Sympathathomimetics EPINEPHRINE
DIPIVEFRIN
Alpha-Adrenergic Agonists APRACLONIDINE
BRIMONIDINE
Prostaglandin Analogues LATANOPROST
UNOPROSTONE
TRAVOPROST
3827_Ch26_837-862 02/07/15 12:00 PM Page 851
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
852
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853
Table 26–7 " Dosage Schedule: Selected Ocular Antiallergic and Anti-Inflammatory Agents
Drug Indication Dosage Form Dose Notes
Mast Cell Stabilizers
Antihistamines
3827_Ch26_837-862 02/07/15 12:00 PM Page 853
854
Table 26–7 " Dosage Schedule: Selected Ocular Antiallergic and Anti-Inflammatory Agents—cont’d
Drug Indication Dosage Form Dose Notes
NSAIDs
Rational Drug Selection
Monitoring
Patient Education
OCULAR LUBRICANTS
3827_Ch26_837-862 02/07/15 12:00 PM Page 854
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
855
Table 26–8 " Dosage Schedule: Miscellaneous Ophthalmic Products
Drug Indication Dosage Forms Dose Comments
Ocular Lubricants
Ophthalmic Vasoconstrictors
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856
Table 26–8 " Dosage Schedule: Miscellaneous Ophthalmic Products—cont’d
Drug Indication Dosage Forms Dose Comments
Ophthalmic Diagnostic Products
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
OPHTHALMIC VASOCONSTRICTORS
Pharmacodynamics
Pharmacokinetics
3827_Ch26_837-862 02/07/15 12:00 PM Page 856
857
Rational Drug Selection
Patient Education
OPHTHALMIC DIAGNOSTIC PRODUCTS
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Patient Education
DRUGS USED IN TREATING EAR DISORDERS OTIC ANTIINFECTIVES
3827_Ch26_837-862 02/07/15 12:00 PM Page 857
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
858
3827_Ch26_837-862 02/07/15 12:00 PM Page 858
859
Table 26–9 " Dosage Schedule: Drugs Used in Treating Ear Disorders
Drug Indication Dosage Forms Dose Comments
Otic Anti-Infectives
Otic Anti-Infective- Steroid Combination
3827_Ch26_837-862 02/07/15 12:00 PM Page 859
860
Table 26–9 " Dosage Schedule: Drugs Used in Treating Ear Disorders—cont’d
Drug Indication Dosage Forms Dose Comments
Acid–Alcohol Solutions
Otic Analgesics
Ceruminolytics
Monitoring
Patient Education
3827_Ch26_837-862 02/07/15 12:00 PM Page 860
OTIC ANALGESICS
CERUMINOLYTICS
REFERENCES
861
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3827_Ch26_837-862 02/07/15 12:00 PM Page 862
UNIT III
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3827_Ch27_863-880 01/07/15 6:19 PM Page 864
865
A PATHOPHYSIOLOGY COMMON TO ALL ANEMIAS
CHAPTER 27
Teri Moser Woo • Kristen Osborn
PATHOPHYSIOLOGY COMMON TO ALL ANEMIAS, 865 Iron Deficiency Anemia
Folic Acid Deficiency Anemia
Pernicious Anemia
Anemia of Chronic Disease
Sickle Cell Anemia
GOALS OF TREATMENT, 870
RATIONAL DRUG SELECTION, 870 Iron Deficiency Anemia
Folic Acid Deficiency Anemia
Pernicious Anemia
Anemia of Chronic Disease
Sickle Cell Anemia
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866
Table 27–1 Normal Blood Values by Age and Gender
Mean Corpuscle Mean Corpuscle Volume (mcg3) Hemoglobin RBC
Hemoglobin RBC Count Concentration Concentration Distribution Age/Gender (g/100 mL) Hematocrit (million/mm3) (pg/cell) (pg/cell) Width
Iron Deficiency Anemia (IDA)
3827_Ch27_863-880 01/07/15 6:19 PM Page 866
867
Disease process erythropoiesis, blood loss, or RBC destruction
Compensatory mechanisms
Renal Heart rate DPG in cells
Heart angina
Erythropoietin Stroke volume
Hyperdynamic circulation
High-output heart failureCardiac murmurs
Cardiovascular
Fatty changes in liver and kidneyIschemia Hypoxia
Release of O2 from Hb to tissues
RBCs, Hb anemia
Claudication (muscles)
Stimulates bone marrow
Weakness and fatigue
Respiratory rate, depth, and exertional dyspnea
Dizziness and syncope
Myocardial oxygen demand
Capillary dilation
Pale skin and mucosa
Renin-angiotensin-aldosterone response Na+ and H2O retention ECF volume
Figure 27–1. Progression and manifestations of anemia.
Table 27–2 Laboratory Findings in Selected Anemias
Folic Acid Iron Deficiency Deficiency Pernicious Anemia of Sickle
Test Anemia Anemia Anemia Chronic Disease Cell Anemia
3827_Ch27_863-880 01/07/15 6:19 PM Page 867
Folic Acid Deficiency Anemia (FOA)
Pernicious Anemia (PA)
868
3827_Ch27_863-880 01/07/15 6:19 PM Page 868
Anemia of Chronic Disease (ACD)
Sickle Cell Anemia (SCD)
869
3827_Ch27_863-880 01/07/15 6:19 PM Page 869
GOALS OF TREATMENT
RATIONAL DRUG SELECTION
Iron Deficiency Anemia (IDA) Risk Stratification and Screening
870
3827_Ch27_863-880 01/07/15 6:19 PM Page 870
Prevention of IDA
Drug Therapy
871
Table 27–3 Iron Intake Recommendations for the Prevention and Treatment of Iron Deficiency Anemia
Risk Group Prevention Treatment
3827_Ch27_863-880 01/07/15 6:19 PM Page 871
Monitoring
Outcome Evaluation
872
Poor utilization? Evaluate and treat for: chronic inflammation,
lead poisoning
Trial of oral ferrous sulfate for 4–6 weeks
Hemoglobin and hematocrit at 4 weeks
If severe anemia, reticulocyte count after 5–10 days
Adequate response Inadequate response
Continue oral iron for 6–12 months to replenish iron stores
Hemoglobin, hematocrit, and ferritin levels at 3 months
Inadequate dose? Increase dose and
recheck hemoglobin and hematocrit
Consult/refer
Adherence? Explore reasons Patient education
Hemoglobin less than 7 mg/dL
Unable to determine reason for
inadequate response
Malabsorption of iron? Evaluate
for gastroenteropathy
Figure 27–2. Drug treatment algorithm for iron deficiency anemia.
3827_Ch27_863-880 01/07/15 6:19 PM Page 872
Lifestyle Modifications
Drug Therapy
873
PATIENT EDUCATION PA TIENT
EDUCATI ON
Patient education related to IDA should focus on:
1. Understanding the pathophysiology of IDA and its potential long-term effects.
2. Recognizing the importance of prevention and the role of diet and energy conservation.
3. Understanding the necessity of adherence to the treatment regimen.
4. Understanding the need for follow-up visits with the primary care provider because IDA can recur.
Stress to the patient that a diet with sufficient amounts of iron-rich foods may avoid the need for sup- plemental iron therapy but only after the IDA has been resolved. When diet alone is inadequate or when iron needs are very high, as in pregnancy, drug therapy is initiated. Patient education specific to drug therapy includes the following:
1. The reason for taking iron. 2. Doses and schedules for the drug. 3. Potential drug interactions and the need to in-
form other providers that they are taking iron. 4. Possible adverse reactions and ways to reduce
them. The most common adverse reactions that lead to nonadherence are GI problems such as nausea and constipation. Taking iron with food reduces the total amount absorbed but can also reduce the nausea. Adequate fluids and fiber can prevent constipation. Stool softeners may be needed to treat constipation associated with iron therapy.
Additional patient education related to iron therapy is presented in Chapter 18.
Folic Acid Deficiency Anemia Risk Groups
3827_Ch27_863-880 01/07/15 6:19 PM Page 873
Monitoring
Pernicious Anemia (PA) Risk Groups
Lifestyle Modifications
Drug Therapy
874
PATIENT EDUCATION PA TIENT
EDUCATI ON
Patient education for folic acid deficiency anemia focuses on prevention as well as treatment. Diet and appropriate cooking methods are central to prevention, especially for strict vegetarians. The need for folic acid supplementation should be discussed with women of childbearing age. When diet alone is inadequate or folate needs are very high, as in pregnancy, drug therapy is initiated. Patient education specific to drug therapy includes the following:
1. The reason for taking folic acid. 2. The doses and schedule for the drug. 3. The fact that some drugs may potentially inter-
fere with folate metabolism. 4. The need to inform their providers that they are
taking supplemental folic acid.
More specific discussion of patient education is found in Chapter 18.
3827_Ch27_863-880 01/07/15 6:19 PM Page 874
Monitoring
Anemia of Chronic Disease Risk Stratification and Screening
Treatment of ACD
875
PATIENT EDUCATION PA TIENT
EDUCATI ON
Patient education related to pernicious anemia (PA) should focus on:
1. Understanding the pathophysiology of PA and its potential long-term effects.
2. The importance of adherence to the treatment regimen.
3. The need for follow-up visits with the primary care provider in that PA and its symptoms can recur, even with continuing therapy.
Patient education specific to the drug therapy in- cludes the following:
1. The reason for taking vitamin B12. 2. The fact that the oral vitamin B12 found in multi-
vitamin tablets is not sufficient to treat the problem.
3. The doses and schedule for the drug. 4. The fact that patients need to take the drug for
the rest of their lives.
3827_Ch27_863-880 01/07/15 6:19 PM Page 875
Sickle Cell Anemia
Prevention
Dietary Counseling
Drug Therapy
876
3827_Ch27_863-880 01/07/15 6:19 PM Page 876
877
PATIENT EDUCATION P ATIENT
EDUCATI ON
Patient and parental information related to sickle cell anemia should focus on the following:
1. Understanding the pathophysiology of SCD and the organs commonly damaged. 2. Recognizing the importance of prevention, especially the central role of prevention of infection and avoidance
of precipitants of sickling. 3. Learning how to administer prophylactic antibiotics and other drugs. 4. Understanding the necessity of adherence to the treatment regimen. 5. Recognizing the need for regular follow-up visits with a primary care provider to manage this chronic disease. 6. Understanding the role of genetic counseling.
Prevention of sickling requires the parents and the patient to learn specific assessment skills. Any sign of illness in a child with SCD can be serious.
Patient education related to the administration of penicillin is discussed in Chapter 24. Measures to minimize the risk of vaso-occlusive events beyond prevention of infection were discussed previously. The
hazards of cigarette smoking and excessive alcohol intake and the benefits of a well-planned exercise program should be included.
Although IDA is not common for patients with SCD, prevention of IDA with a diet that includes sufficient amounts of iron-rich foods should be discussed. When iron is required, follow the patient education instructions for IDA.
Patient education specific to the use of hydroxyurea includes the following:
1. Take the drug exactly as prescribed, even if nausea, vomiting, or diarrhea occurs. 2. If a dose is missed, do not take it at all; do not double dose. 3. Notify the health-care provider of fever; chills; sore throat; loss of appetite; nausea; vomiting; diarrhea; bleeding
gums; bruising; petechiae; or blood in the urine, stool, or emesis. 4. Avoid alcoholic beverages, aspirin, and NSAIDs, which may increase the risk of bleeding. 5. Inspect oral mucosa for erythema and ulceration. If it occurs, use a sponge brush and rinse mouth with water after
eating and drinking. If mouth pain interferes with eating, contact the health-care provider for lidocaine-based mouthwash.
6. Encourage fluid intake of 2,000 to 3,000 mL of noncaffeinated fluid daily. 7. Review the need for contraception during therapy because of the teratogenic potential of this drug.
Patient education related to the other drugs used in treatment of SCD and its complications is presented in the Unit II chapters that include these drugs. Patient education related to the other complications of SCD is detailed in the NIH publi- cations in the References section.
Transfusions
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Monitoring
Outcome Evaluation
REFERENCES
878
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879
3827_Ch27_863-880 01/07/15 6:19 PM Page 879
3827_Ch27_863-880 01/07/15 6:19 PM Page 880
881
CHAPTER 28
Laura D. Rosenthal
PATHOPHYSIOLOGY, 881
PHARMACODYNAMICS, 883
GOALS OF TREATMENT, 884
RATIONAL DRUG SELECTION, 884 Risk Stratification
Treatment Algorithms
Lifestyle Modification
Drug Therapy
Additional Patient Variables
Cost
MONITORING, 893
OUTCOME EVALUATION, 893
PATIENT EDUCATION, 895
A
PATHOPHYSIOLOGY
3827_Ch28_881-896 01/07/15 6:15 PM Page 881
882
Decreased oxygen transport to myocardium
ATP formation
Glycolysis Na+ pump
Glycogen
Lactate
pH
Mitochondrial oxygenation
Myocardial ischemia
Release of lysosomal enzymes
Adrenergic stimulation
Cellular autodigestion
Mitochondrial contraction
Mitochondrial swelling
Ca2+ influx and uptake in mitochondria
Peripheral vasoconstriction
Pump failure
Fall in cardiac output
Fall in arterial output
SNS stimulation
Na+/K+, Ca2+/Mg++
Release of CPK and AST enzymes
ECF volume
Afterload
Increased oxygen demand
Decreased oxygen supply
Myocardial injury and death
Peripheral vasoconstriction
Heart rate
Contractility
H2O
Figure 28–1. Pathophysiology of myocardial ischemia.
3827_Ch28_881-896 01/07/15 6:15 PM Page 882
PHARMACODYNAMICS
883
3827_Ch28_881-896 01/07/15 6:15 PM Page 883
GOALS OF TREATMENT
RATIONAL DRUG SELECTION
Risk Stratification Major Risk Factors
884
3827_Ch28_881-896 01/07/15 6:15 PM Page 884
Noncardiac Factors
Classification System for Grading Angina
Treatment Algorithms
885
Table 28–1 Grading of Angina by the New York Heart Association and the Canadian Cardiovascular Society
Class New York Heart Association Canadian Cardiovascular Society
3827_Ch28_881-896 01/07/15 6:15 PM Page 885
886
Table 28–2 Risk Profiles Associated With Angina
Risk Lifestyle Risk Physiological Risk
Table 28–3 American College of Cardiology/American Heart Association Risk Stratification in Patients With Chronic Stable Angina
Class Description
Lifestyle Modification
3827_Ch28_881-896 01/07/15 6:15 PM Page 886
Drug Therapy Initial Therapy for Symptomatic Patients
887
Table 28–4 Lifestyle Modifications
Attain Ideal Body Weight.
Increase Aerobic Physical Activity Within the Limitations of Angina.
Reduce Daily Sodium Intake to No More Than 1,500 mg.
Maintain Adequate Intake of Dietary Potassium (Approximately 60 mEq/d).
Reduce Intake of Dietary Saturated Fats and Cholesterol.
Stop Smoking.
Limit Alcohol Intake.
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888
Table 28–5 Drug Choice Based on Concomitant Disease States
Drug Choice Favorable Effects Unfavorable Effects
Nitrates
Beta-Adrenergic Blockers
ACE Inhibitors
Direct Renin Inhibitors
HMG-CoA Reductase Inhibitors (Statins)
Calcium Channel Blockers
3827_Ch28_881-896 01/07/15 6:15 PM Page 888
Multidrug Therapy
889
3827_Ch28_881-896 01/07/15 6:15 PM Page 889
Drug Therapies That Are Not Helpful and/or Are to Be Avoided
Additional Patient Variables Older Adults
Women
Concomitant Diseases
890
3827_Ch28_881-896 01/07/15 6:15 PM Page 890
891
3827_Ch28_881-896 01/07/15 6:15 PM Page 891
Cost
892
Table 28–6 Drugs Commonly Used: Angina
Drug Brand Name
ACE Inhibitors
Direct Renin Inhibitors
Beta-Adrenergic Blockers
Calcium Channel Blockers
Nitrates
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MONITORING
OUTCOME EVALUATION
893
3827_Ch28_881-896 01/07/15 6:15 PM Page 893
894
Treat any concomitant diseases Begin lifestyle modifications
Start patient on aspirin 81–325 mg/day
Angina not under control or grade not reduced
Angina still not under control or grade not reduced
Angina still not under control or grade not reduced
Angina still not under control or grade not reduced
Add drugs for patient with concomitant disease or therapies if not already taking (see Table 28–5) or increase dose of one or more of initial drugs
Add beta blocker for all patients with
or without previous MI†
Add ACE inhibitor for all patients with
LV dysfunction‡
Add statin for all patients with LDL >100 mg/dL
Add sublingual or spray nitroglycerine (NTG) for symptom management*
Initial drug choices
Consider referral to cardiology specialist§
* If patient nitrate intolerant, may use calcium channel blocker for symptom relief. † If beta blocker contraindicated or has unacceptable side effects, may use calcium channel
blocker or long-acting nitrate. ‡ ACC/AHA recommends ACE inhibitors for diabetics and patients with LV dysfunction;
American College of Physicians recommends for all with no restrictions. § ACC/AHA class I patients may require initial referral to cardiology specialist; consultation
should occur whenever needed in planning care for all classes.
Figure 28–2. Drug treatment protocol for chronic stable angina and low-risk unstable angina.
3827_Ch28_881-896 01/07/15 6:15 PM Page 894
PATIENT EDUCATION
REFERENCES
895
PATIENT EDUCATION: ANGINA P ATIENT
EDUCATI ON
Related to the Overall Treatment Plan/Disease Process
■■ Pathophysiology of angina and its prognosis
■■ Role of lifestyle modifications in improving prognosis and keeping down the number and cost of required drugs
■■ Importance of adherence to the treatment regimen
■■ Indications of complications that need to be reported and the need for regular follow-up visits with the primary care provider
Specific to the Drug Therapy
■■ Reason for taking the drug(s) and the anticipated action of the drug(s) on the disease process
■■ Doses and schedules for taking the drugs
■■ Possible adverse reactions and what to do when they occur
■■ Interactions between lifestyle modification and these drugs
Reasons for Taking the Drug(s)
Specific information related to angina includes reasons for the drugs being given. Antianginal drugs are given to reduce cardiovascular morbidity (especially MI) and mortality. Some drugs do both of these things; most do either one or the other. The expectation should be clear about what these drugs can and cannot do. Stable angina is a chronic condition that re- quires lifelong treatment, and so the regimen should be incorporated into the daily life of the patient. Even well-managed angina can become unstable and may require urgent management. Knowledge of when and how to use sublingual or translingual nitroglycerin is important.
Drugs as Part of the Total Treatment Regimen
Angina therapy is based on lifestyle modification. These modifications are not always easy to maintain, but they are equally as important as drugs in successful control of symptoms and prevention of complications. Among the lifestyle modifica- tions is sodium restriction to reduce extracellular fluid volume, decrease afterload, and reduce MOD. Care should be taken not to reduce salt and fluid too quickly, which may result in fluid volume deficit, leading to hypotension and a reduction in MOS. Patients should be taught signs and symptoms of fluid volume deficit to report. None of the antianginal drugs directly reduces fluid volume, but all except aspirin have vasodilating actions that may make fluid volume deficit worse. Sodium reduction may also lead some patients to seek salt substitutes that have potassium as part of their contents. Changes in potassium levels can significantly affect myocardial functioning, so these substitutes should be used sparingly. Use of nonsalt herbal seasoning is encouraged.
Another central lifestyle modification is regular aerobic exercise, such as walking or cycling. The amount and type of exercise must be carefully monitored and targeted to anginal symptoms. Patients can be referred to a cardiac rehabilitation program at the start of their exercise program so that their response can be monitored. Later, they can monitor their own response and determine the pace and amount of exercise that works for them. The key is gradually increasing regular aerobic exercise. Several of the antianginal drugs, especially the nitrates, have the potential to cause orthostatic hypoten- sion. Exercise should be timed to avoid this adverse reaction, and adequate fluids should be taken while exercising.
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896
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897
CHAPTER 29
Mary Weber • Krista Estes
ASSESSMENT AND SCREENING, 898
NEUROBIOLOGY, 899
EVIDENCEDBASED TREATMENTS OF MAJOR DEPRESSIVE DISORDER AND ANXIETY DISORDERS, 900
CLASSES OF MEDICATIONS, 901 Nonselective Norepinephrine-Serotonin Reuptake
Inhibitors
Serotonin-Selective Reuptake Inhibitors (SSRI)
Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)
Norepinephrine-Dopamine Reuptake Inhibitors
Serotonin Agonist Reuptake Inhibitors (SARI)
Norepinephrine- and Serotonin-Specific Agonist (NaSSA)
Monoamine Oxidase Inhibitors (MAOI)
Benzodiazepines/GABA-ergics (BZDs)
ADVERSE DRUG REACTIONS, 905
RATIONAL DRUG SELECTION, 905 General Principles in Selecting an Initial Antidepressant
Anxiety
Post-traumatic Stress Disorder
Obsessive-Compulsive Disorder
MONITORING AND PATIENT EDUCATION, 906
COMORBIDITY OF MEDICAL AND PSYCHIATRIC DISORDERS, 908
SPECIAL POPULATIONS, 908
OUTCOME EVALUATION, 909
CONCLUSIONS, 910
A
3827_Ch29_897-912 01/07/15 6:12 PM Page 897
ASSESSMENT AND SCREENING
898
3827_Ch29_897-912 01/07/15 6:12 PM Page 898
NEUROBIOLOGY
899
Table 29–1 SAFE-T Assessment of Suicide Risk
Suicide Assessment Five-Step Evaluation and Triage
3827_Ch29_897-912 01/07/15 6:12 PM Page 899
EVIDENCE-BASED TREATMENTS OF MAJOR DEPRESSIVE DISORDER AND ANXIETY DISORDERS
900
3827_Ch29_897-912 01/07/15 6:12 PM Page 900
CLASSES OF MEDICATIONS
901
Evaluate for comorbidity, suicidality, medical reasons for insomnia, substance
abuse, noncompliance, childbearing potential, elderly patient, and
cultural issues.
General Algorithim for the Treatment of Depression Based on STAR*D Effectiveness Research
Start SSRI #1 and refer to
mental health provider for therapy.
Lack of Remission or Poor Response?
Refer to psychiatric provider.
SSRI #2 NDRI SNRI + NDRI + 5HT1A
Switch options Augmentation options
Figure 29–1. General algorithm for the treat- ment of depression based on the STAR*D effectiveness research.
General Algorithim for the Treatment of Adults With Anxiety Disorders
Screen for medical, psychiatric, and
substance comorbidities.
Start an SSRI or SNRI and refer to mental health
provider for therapy.
Lack of Remission or Poor Response?
Refer to psychiatric provider.
Screen for anxiety disorders.
Figure 29–2. General algorithm for the treatment of anxiety disorders.
3827_Ch29_897-912 01/07/15 6:12 PM Page 901
Nonselective Norepinephrine-Serotonin Reuptake Inhibitors Serotonin-Selective Reuptake Inhibitors
902
Table 29–2 ! Four Cytochrome P-450 Isoenzymes and Potential Drug Interactions
Isoenzyme Substrates Inhibitors
3827_Ch29_897-912 01/07/15 6:12 PM Page 902
Serotonin-Norepinephrine Reuptake Inhibitors
Norepinephrine-Dopamine Reuptake Inhibitors
903
3827_Ch29_897-912 01/07/15 6:12 PM Page 903
Serotonin Agonist Reuptake Inhibitors
Norepinephrine- and Serotonin-Specific Agonist
Monoamine Oxidase Inhibitors (MAOI) Benzodiazepines/GABA-ergics (BZDs)
904
On The Horizon PSYCHOPHARMACOLOGY RESEARCH
What to look for during the next 5 years in psychopharmacology:
• New mechanisms of action, especially targeting glutamate/GABA interaction
• Targeting antagonism of the glutamate receptor to treat depression
• Development of drugs targeting the second messenger system for faster response rates and possibly neuro- protective qualities in preventing further depression
• Corticotropin-releasing factor antagonists to mediate effects of stress on the pathophysiology of depression
3827_Ch29_897-912 01/07/15 6:12 PM Page 904
ADVERSE DRUG REACTIONS
RATIONAL DRUG SELECTION
General Principles in Selecting an Initial Antidepressant
905
3827_Ch29_897-912 01/07/15 6:12 PM Page 905
Anxiety
Post-Traumatic Stress Disorder
Obsessive-Compulsive Disorder
MONITORING AND PATIENT EDUCATION
906
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907
Table 29–3 When to Refer
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COMORBIDITY OF MEDICAL AND PSYCHIATRIC DISORDERS
SPECIAL POPULATIONS
908
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OUTCOME EVALUATION
909
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REFERENCES
910
CLINICAL PEARLS
Treatment and Monitoring of Patients with Anxiety and Depression
1. Always evaluate a patient for hypomania or mania before starting an antidepressant because these conditions can worsen bipolar symptoms.
2. When there is any anxiety disorder, consider start- ing all antidepressants low and going slow.
3. Start low and go slow when treating older adults with depression and/or anxiety.
4. Always monitor for suicidal thoughts throughout the entire treatment.
5. Always discuss the risks of fetal damage with a woman of childbearing potential who is taking an antidepressant BEFORE she gets pregnant so that she knows the risks and benefits of treatment.
6. Always monitor for signs and symptoms of serotonin syndrome, especially asking about new medications prescribed or any over-the-counter medications taken.
7. Taper off antidepressants slowly; most have dis- continuation side effects.
8. Withdrawal or discontinuation symptoms include dizziness, nausea, diarrhea, sweating, irritability, and increased anxiety. If these occur, raise the dose to stop symptoms and taper even more slowly.
9. Do not start monoamine oxidase inhibitors (MAOIs) within 14 days of stopping other antidepressants; do not start another antidepressant until 14 days after stopping an MAOI.
10. It is tempting for both the patient and primary care provider to attribute success to the medications, but to do so invalidates the power and capacity of patients.
11. Medications can only help the brain return to its nor- mal functioning. It is the whole person who makes the changes necessary for recovery to mental health.
CONCLUSIONS
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911
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912
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913
CHAPTER 30
Benjamin J. Miller
ASTHMA, 913 Pathophysiology
Goals of Therapy
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
CHRONIC OBSTRUCTIVE PULMONARY DISEASE, 935 Pathophysiology
Goals of Therapy
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
A
ASTHMA
Pathophysiology
3827_Ch30_913-942 01/07/15 6:11 PM Page 913
914
Chronic Inflammation
Airway Hyperresponsiveness
Neutrophil
Mast cell
IL-3, IL-4, IL-13, IL-9
Eosinophil
IL-3, IL-5 GM-CSF
IgE
I n f la
m a t
i o n
Th2/Th1 cytokines (e.g.,
B lymphocyte T lymphocyte
Acute inflammation
Environmental factors
A irw
ay m icroenvironm
ent
Initiation
Amplification
Propagation
Blood vessels Smooth muscle
Pro-inflammatory mediators
m
IL-13, TNF- !)
Airway Effects Bronchospasm
Acute inflammation Persistent inflammation
RemodelingTNF-!
Dendritic cell
(myo) fibroblasts
Environmental factors and inflammatory products
Mucus
Persistent inflammation and development of remodeling
Figure 30–1. Factors limiting airflow in acute and persistent asthma. Key: GM-CSF, granulocyte-macrophage colony-stimulating factor; IgE, immunoglobulin E; IL-3, interleukin 3 (and similar); TNF-!, tumor necrosis factor-alpha. (Source: Holgate, S. T., & Polosa, R. [2006]. The mecha- nisms, diagnosis, and management of severe asthma in adults. The Lancet, 368, 780–793.)
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Airflow Obstruction
Classification of Asthma
915
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916
Goals of Therapy
Reduce Impairment Reduce Risk
Table 30–1 Classification of Asthma Severity 12 Years of Age
Components of Severity
Impairment
Normal FEV1/FVC:
Risk
Recommended Step for Initiating Treatment. (See ”Stepwise Approach for Managing Asthma” for treatment steps.)
Classification of Asthma Severity 12 years of age
Intermittent Mild Moderate Severe
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917
SY M
P T
O M
S
A ge
s 0–
4 A
ge s
0– 4
A ge
s 0–
4
Ta b
le 3
0– 2
C la
ss if
ic at
io n
o f A
st h
m a
Se ve
ri ty
a n
d In
it ia
l T h
er ap
y in
C h
ild re
n C la
ss if
yi n
g A
st h
m a
Se ve
ri ty
a n
d In
it ia
ti n
g T
h er
ap y
in C
h il
d re
n
C o
m p
o n
en ts
o f S
ev er
it y
Im p
ai rm
en t
R is
k
R ec
o m
m en
d ed
S te
p fo
r In
it ia
ti n
g
T h
er ap
y. (S
ee “
St ep
w is
e A
p p
ro ac
h
fo r
M an
ag in
g A
st h
m a”
fo r
tr ea
tm en
t st
ep s.
)
In te
rm it
te n
t M
ild M
o d
er at
e Se
ve re
A ge
s 0–
4
3827_Ch30_913-942 01/07/15 6:11 PM Page 917
Rational Drug Selection Asthma Step Therapy
Initiating Control of Asthma
918
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919
Table 30–3 Assessing Asthma Control and Adjusting Therapy in Youths 12 Years and Adults
Classification of Asthma Control ( 12 years of age)
Components of Control
Impairment
Risk
Recommended Action for Treatment
SYMPTOMS
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920
Table 30–4 Assessing Asthma Control and Adjusting Therapy in Children
Assessing Asthma Control and Adjusting Therapy in Children
Components of Control
Impairment
Risk
Recommended Action for Treatment (See “Stepwise Approach for Managing Asthma” for treatment steps.)
Ages 0–4 Ages 0–4 Ages 0–4
SYMPTOMS
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921
Table 30–5 Stepwise Approach for Managing Asthma in Youths >12 Years and Adults
Intermittent Asthma
Persistent Asthma: Daily Medication Consult with asthma specialist if step 4 or higher is required.
Consider consultation at step 3.
Step 1 Preferred: SABA PRN
Step 2 Preferred: Low-dose ICS
Alternative: Cromolyn, LTRA, Nedocromil, or Theophylline
Step 3 Preferred: Low-dose ICS + LABA or Medium-dose ICS
Alternative: Low-dose ICS + either LTRA, Theophylline, or Zileuton
Step 4 Preferred: Medium-dose ICS + LABA
Alternative: Medium-dose ICS + either LTRA, Theophylline, or Zileuton
Step 5 Preferred: High-dose ICS + LABA
and Consider Omalizumab for patients who have allergies
Step 6 Preferred: High-dose ICS + LABA + oral corticosteroid
and Consider Omalizumab for patients who have allergies
Quick-Relief Medication for All Patients • SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms:
up to 3 treatments at 20-minute intervals as needed. Short course of oral systemic corticosteroids may be needed.
• Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step up treatment.
Key: Alphabetical order is usually more than one treatment option listed within either preferred or alternative therapy. ICS, inhaled corticosteroid; LABA, inhaled long-acting beta2-agonist, LTRA, leukotriene receptor antagonist; SABA, inhaled short-acting beta2-agonist.
Notes:
• The stepwise approach is meant to assist, not replace, the clinical decision making required to meet individual patient needs.
• If alternative treatment is used and response is inadequate, discontinue it and use the preferred treatment before stepping up.
• Zileuton is a less desirable alternative due to limited studies as adjunctive therapy and the need to monitor liver function. Theophylline requires monitoring of serum concentration levels.
• In step 6, before oral corticosteroids are introduced, a trial of high-dose ICS + LABA + either LTRA, theophylline, or zileuton may be considered, although this approach has not been studied in clinical trials.
• Step 1, 2, and 3 preferred therapies are based on Evidence A; step 3 alternative therapy is based on Evidence A for LTRA, Evidence B for theophylline, and Evidence D for zileuton. Step 4 preferred therapy is based on Evidence B, and alternative therapy is based on Evidence B for LTRA and theophylline and Evidence D zileuton. Step 5 preferred therapy is based on Evidence B. Step 6 preferred therapy is based on (EPR—2 1997) and Evidence B for omalizumab.
• Immunotherapy for steps 2–4 is based on Evidence B for house-dust mites, animal danders, and pollens; evidence is weak or lacking for molds and cockroaches. Evidence is strongest for immunotherapy with single allergens. The role of allergy in asthma is greater in children than in adults.
• Clinicians who administer immunotherapy or omalizumab should be prepared and equipped to identify and treat anaphylaxis that may occur.
Step up if needed
(first, check adherence,
environmental control, and
comorbid conditions)
Step down if possible
(and asthma is well
controlled at least 3 months)
Assess control
Each step: Patient education, environmental control, and management of comorbidities Steps 2–4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma (see notes).
Stepwide Approach for Managing Asthma in Youths 12 Years of Age and Adults
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922
Table 30–6 Stepwise Approach for Managing Asthma Long Term in Children
Intermittent Asthma
Persistent Asthma: Daily Medication Consult with asthma specialist if step 4 or higher is required. Consider consultation at step 3. • The stepwise approach is meant to assist, not replace, the clinical
decision making required to meet individual patient needs. • If alternative treatment is used and response is inadequate, discontinue it
and use the preferred treatment before stepping up. • If clear benefit is not observed within 4–6 weeks, and patient's/family's
medication technique and adherence are satisfactory, consider adjusting therapy or an alternative diagnosis.
• Studies on children 0–4 years of age are limited. Step 2 preferred therapy is based on Evidence A. All other recommendations are based on expert opinion and extrapolation from studies in older children.
• Clinicians who administer immunotherapy or omalizumab should be prepared and equipped to identify and treat anaphylaxis that may occur.
Key: Alphabetical order is usually more than one treatment option listed within either preferred or alternative therapy. ICS, inhaled corticosteroid; LABA, inhaled long-acting beta2-agonist, LTRA, leukotriene receptor antagonist; SABA, inhaled short-acting beta2-agonist.
• The stepwise approach is meant to assist, not replace, the clinical decision making required to meet individual patient needs.
• If alternative treatment is used and response is inadequate, discontinue it and use the preferred treatment before stepping up.
• Theophylline is a less desirable alternative due to the need to monitor serum concentration levels.
• Steps 1 and 2 medications are based on Evidence A. Step 3 ICS and ICS plus adjunctive therapy are based on Evidence B for efficacy of each treatment and extrapolation from comparator trials in older children and adults—comparator trials are not available for this age group: steps 4–6 are based on expert opinion and extrapolation from studies in older children and adults.
• Immunotherapy for steps 2–4 is based on Evidence B for house-dust mites, animal danders, and pollens: evidence is weak or lacking for molds and cockroaches. Evidence is strongest for immunotherapy with single allergens. The role of allergy in asthma is greater in children than adults.
• Clinicians who administer immunotherapy or omalizumab should be prepared and equipped to identify and treat anaphylaxis that may occur.
Key: Alphabetical order is usually more than one treatment option listed within either preferred or alternative therapy. ICS, inhaled corticosteroid; LABA, inhaled long-acting beta2-agonist, LTRA, leukotriene receptor antagonist; SABA, inhaled short-acting beta2-agonist.
Step up if needed (first, check adherence, environmental control, and comorbid conditions)
Step down if possible (and asthma is well controlled at least 3 months) Assess control
Stepwide Approach for Managing Asthma Long Term in Children 0–4 Years and 5–11 Years of Age
NotesStep 1 Step 2
Step 3 Step 4
Step 5 Step 6
SABA PRN
Each step: Patient education and environmental control
Preferred
Alternative
Low-dose ICS
Cromolyn or Montelukast
Medium-dose ICS
Medium-dose ICS + LABA or Montelukast
High-dose ICS + LABA or Montelukast
High-dose ICS + LABA or Montelukast + Oral corticosteriods ICS
Intermittent Asthma
Persistent Asthma: Daily Medication Consult with asthma specialist if step 4 or higher is required. Consider consultation at step 3.
SABA PRNPreferred
Alternative
Low-dose ICS
Cromolyn, LTRA, Nedocromil, or Theophylline
Low-dose ICS + LABA, LTRA, or Theophylline or Medium-dose ICS
Medium-dose ICS + LABA
High-dose ICS + LTRA or Theophylline
High-dose ICS + LTRA or Theophylline + Oral corticosteriods
Medium-dose ICS + LTRA or Theophylline
High-dose ICS + LABA
High-dose ICS + LABA + Oral corticosteriods
Quick-Relief Medication
• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms.
• With viral respiratory symptoms: SABA q 4–6 hours up to 24 hours (longer with physician consult). Consider short course of oral systemic corticosteroids if exacerbation is severe or patient has history of previous severe exacerbations.
Caution: Frequent use of SABA may indicate the need to step up treatment See text for recommendations on initiating dairy long-term-control therapy.
Each step: Patient education, environmental control, and management of comorbidities Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have persistent, allergic asthma.
Quick-Relief Medication
• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals as needed. Short course of oral systemic corticosteroids may be needed.
Caution: Increasing use of SABA or use >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step up treatment.
C h
ild re
n 0
–4 Y
e a
rs o
f A
g e
C h
ild re
n 5
–1 1
Y e
a rs
o f
A g
e
Table 30–7 Drugs Commonly Used: Asthma and COPD
Drug Dosage How Supplied Comments
Short-Acting Bronchodilators
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923
Table 30–7 Drugs Commonly Used: Asthma and COPD—cont’d
Drug Dosage How Supplied Comments
Long-Acting Bronchodilator
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924
Table 30–7 Drugs Commonly Used: Asthma and COPD—cont’d
Drug Dosage How Supplied Comments
Anticholinergic Agents
Combination Inhaled Medications
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925
Table 30–7 Drugs Commonly Used: Asthma and COPD—cont’d
Drug Dosage How Supplied Comments
Systemic Corticosteroids
Inhaled Anti-Inflammatory Agents
Inhaled Corticosteroids
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926
Table 30–7 Drugs Commonly Used: Asthma and COPD—cont’d
Drug Dosage How Supplied Comments
Leukotriene Modifiers
3827_Ch30_913-942 01/07/15 6:11 PM Page 926
927
Ta b
le 3
0– 8
C o
m p
ar at
iv e
D ai
ly D
o sa
g es
fo r
In h
al ed
C o
rt ic
o st
er o
id s
Lo w
D ai
ly D
o se
M ed
iu m
D ai
ly D
o se
H ig
h D
ai ly
D o
se
D ru
g
B ec
lo m
et h
as o
n e
H FA
B u
d es
o n
id e
D P
I
B u
d es
o n
id e
In h
al ed
Fl u
n is
o li
d e
Fl u
n is
o li
d e
H FA
Fl u
ti ca
so n
e H
FA /M
D I:
D P
I:
M o
m et
as o
n e
D P
I
T ri
am ci
n o
lo n
e ac
et o
n id
e
3827_Ch30_913-942 01/07/15 6:11 PM Page 927
Emerging Therapies
Monitoring Control
928
3827_Ch30_913-942 01/07/15 6:11 PM Page 928
Managing Exacerbations
Maintaining Control of Asthma
Home Management of Exacerbations of Asthma
Patient Variables
929
3827_Ch30_913-942 01/07/15 6:11 PM Page 929
930
Assess Severity Patients at high risk for a fatal attack require immediate medical attention after initial treatment. Symptoms and signs suggestive of a more serious exacerbation, such as marked breathlessness, inability to speak more than short phrases, use of accessory muscles, or drowsiness, should result in initial treatment while immediately consulting with a clinician. Less severe signs and symptoms can be treated initially with assessment of response to therapy and further steps as listed below. If available, measure PEF—values of 50%–79% predicted or personal best indicate the need for quick-relief medication. Depending on the response to treatment, contact with a clinician may also be indicated. Values below 50% indicate the need for immediate medical care.
Initial Treatment Inhaled SABA: Up to two treatments 20 minutes apart of 2–6 puffs by metered-dose inhaler (MDI) or nebulizer treatments Note: Medication delivery is highly variable. Children and individuals who have exacerbations of lesser severity may need fewer puffs than suggested above.
Good Response No wheezing or dyspnea (assess tachypnea in young children) PEF "80% predicted or personal best
Contact clinician for follow-up instructions and further management. May continue inhaled SABA every 3–4 hours for 24–48 hours. Consider short course of oral systemic corticosteroids.
Incomplete Response Persistent wheezing and dyspnea (tachypnea) PEF 50%–79% predicted or personal best
Add oral systemic corticosteroid. Continue inhaled SABA. Contact clinician urgently (this day) for further instruction.
Poor Response Marked wheezing and dyspnea PEF <50% predicted or personal best
Add oral systemic corticosteroid. Repeat inhaled SABA immediately. If distress is severe and nonresponsive to initial treatment:
—Call your doctor AND —PROCEED TO ED; —Consider calling 9–1–1
(ambulance transport).
To ED
Figure 30–2. Management of asthma exacerbations: Home treatment. Key: ED, emergency department; MDI, metered-dose inhaler; PEF, peak expiratory flow; SABA, short-acting beta2 agonist (quick-relief inhaler). (Source: From National Asthma Education and Prevention Program [NAEPP]. [2007]. The Expert Panel Report 3: Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Heart, Lung, and Blood Institute, National Institutes of Health.)
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931
3827_Ch30_913-942 01/07/15 6:11 PM Page 931
Special Situations
932
3827_Ch30_913-942 01/07/15 6:11 PM Page 932
Monitoring
Monitoring Signs and Symptoms of Asthma
Monitoring Pulmonary Function
Monitoring Quality of Life and Functional Status
933
3827_Ch30_913-942 01/07/15 6:11 PM Page 933
Monitoring History of Asthma Exacerbations
Monitoring Pharmacotherapy
Monitoring Patient–Provider Communication and Patient Satisfaction
Outcome Evaluation
Patient Education
934
PATIENT EDUCATION P ATIENT
EDUCATI ON
Asthma
RELATED TO THE OVERALL TREATMENT PLAN AND DISEASE PROCESS
BASIC FACTS ABOUT ASTHMA
Use a variety of teaching methods such as illustrations, videos, written pamphlets or books, and models. Repeat key facts at every visit until the patient and/or family demonstrates an understanding of asthma. An example would to be to show the patient a drawing of a normal airway and an airway affected by asthma. The provider can then demonstrate how different medications act on different components of asthma (bronchodilator relaxes smooth muscle, anti-inflammatory decreases inflammation, etc.). This information can be repeated when reviewing medications at each visit until a clear understanding is demonstrated.
MEDICATION SKILLS
This includes proper inhaler use, spacer use if appropriate, when to take quick-relief medications, and nebulizer use if appropriate.
SELF-MONITORING SKILLS
This includes self-assessment of symptoms, peak flow monitoring, and how to record symptoms and peak expiratory flow (PEF) on a self-assessment diary. Recognizing early signs of declining lung function is essential knowledge for the patient and family.
Environmental control and avoidance strategies will enable the patient and family to avoid possible asthma triggers. Discussion of how environmental exposure to allergens and irritants can worsen asthma symptoms and how to avoid trig- gers at home, work, and school will assist patients in learning self-management.
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935
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
PATIENT EDUCATIONcont’d P ATIENT
EDUCATI ON
SPECIFIC TO THE DRUG THERAPY
Reason for the drug being given and its anticipated action in the disease process. Doses and schedules for taking the drug. Coping mechanisms for complex and costly drug regimens. Interactions between other treatment modalities and these drugs.
REASONS FOR THE DRUG(S) BEING TAKEN
Patient education about specific drugs is provided in Chapter 17.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
Information should be provided concerning drugs as part of the total treatment regimen and individualized to the patient’s age and asthma severity.
Many educational resources are available, the best of which are from the National Institutes of Health (NIH) and the Global Initiative for Asthma. These documents include the following:
National Asthma Education Prevention Program (2007). The Expert Panel Report 3: Guidelines for Management of Asthma. Includes copy-ready patient handouts on use of peak flow meter, inhalers, and asthma action plans.
Global Initiative for Asthma (2009). Global strategy for asthma management and prevention. http://www.ginasthma.org. Includes a patient guide to asthma and interactive learning modules on asthma in adults and children.
INTERNET-BASED PATIENT EDUCATION RESOURCES ON ASTHMA
The Expert Panel Report 3: Guidelines can be found at http://www.nhlbi.nih.gov/guidelines/asthma/index.htm and the NIH/WHO Global Initiative for Asthma documents can be found at http:/www.ginasthma.com
Other resources include the following:
Allergy and Asthma Network, Mothers of Asthmatics. http://www.aanma.org/ American Academy of Allergy, Asthma, and Immunology. http://www.aaaai.org Asthma and Allergy Foundation of America. http://www.aafa.org Canadian Network for Respiratory Care. http://www.cnrchome.net/ National Asthma Education and Prevention Program. NHLBI http://www.nhlbi.nih.gov/health/public/lung/index
.htm#asthma National Institutes of Health National Heart Lung and Blood Institute. Asthma. http://www.nhlbi.nih.gov/health/dci/
Diseases/Asthma/Asthma_WhatIs.html
3827_Ch30_913-942 01/07/15 6:11 PM Page 935
Pathophysiology Emphysema
936
Table 30–9 Stages of COPD
Classification Definition by Spirometry
At Risk
Mild
Moderate
Severe
Very Severe
Table 30–10 Clinical Features of Chronic Bronchitis and Emphysema
Characteristic Chronic Bronchitis Emphysema
Age at onset of symptoms
Primary symptoms
Sputum
Chest x-ray
Weight
Total lung capacity
Chest examination
Cor pulmonale with heart failure
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Chronic Bronchitis
Goals of Therapy
Rational Drug Selection
Bronchodilators
937
3827_Ch30_913-942 01/07/15 6:11 PM Page 937
Corticosteroids
Oxygen
938
3827_Ch30_913-942 01/07/15 6:11 PM Page 938
Antibiotics
Leukotrienes
Alpha-Trypsin Augmentation Therapy
Immunizations
Smoking Cessation
Monitoring
939
CLINICAL PEARL
Oxygen Therapy One note of caution in providing oxygen therapy to some patients with COPD who have poor ventilatory ca- pacity: These patients, known as “carbon dioxide retain- ers,” no longer rely on rises in PaCO2 as the primary drive to breathe. If these patients receive too much oxy- gen, raising their PaO2 above their normal baseline, hy- poventilation may occur. This results in CO2 retention and the somnolence, lethargy, and coma that occur with carbon dioxide narcosis. Monitoring arterial blood gases is essential in all patients receiving oxygen therapy.
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Outcome Evaluation
Patient Education
940
PATIENT EDUCATION P ATIENT
EDUCATI ON
Chronic Obstructive Pulmonary Disease
RELATED TO THE OVERALL TREATMENT PLAN AND DISEASE PROCESS
The patient needs to be taught the following areas of self-management:
SMOKING CESSATION
This is a difficult area of education because of the physical and psychological addiction to cigarettes. Many patients have attempted to quit smoking previously and need to be encouraged to try again, using some of the pharmacological interventions available to aid in tobacco cessation.
PATHOPHYSIOLOGY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
A basic understanding of the changes in the pulmonary system that occur with COPD will assist the patient in understanding the role that the different medications play in the treatment regimen.
MEDICATION SKILLS
Patients with COPD often have other chronic illnesses that require routine medications. Administering a complex regimen of multiple medications can be overwhelming, especially to older patients. Written schedules (in large print) and divided pill boxes are two strategies for medication management. Providing the patient with the generic and trade names of med- ications will decrease medication confusion. Having the patient bring all medications in for review will prevent medication errors. Often, the patient may be seeing other providers, including specialists who may also be prescribing medications. It is the role of the primary care provider to coordinate between specialty providers and monitor medications the patient is tak- ing. Encourage patients to use a magnifying glass to read the generic names on the meter dose inhaler (MDI) canisters, as the canister color may change with different brands of the same medication.
SPECIFIC TO THE DRUG THERAPY
Reason for the drug being given and its anticipated action in the disease process. Doses and schedules for taking the drug. Coping mechanisms for complex and costly drug regimens. Interactions between other treatment modalities and these drugs.
CLINICAL PEARL
Influenza Vaccine Reminders The health-care provider should keep an electronic “tickler file” of chronic respiratory patients (those with asthma and COPD) so they can remind patients each fall to get their influenza vaccine.
3827_Ch30_913-942 01/07/15 6:11 PM Page 940
REFERENCES
"
941
PATIENT EDUCATIONcont’d P ATIENT
EDUCATI ON
REASONS FOR THE DRUG(S) BEING TAKEN
Patient education about specific drugs should be provided, including how to use inhalers appropriately.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
The total treatment regimen also includes teaching self-monitoring skills, including, if indicated, proper use of a peak flow meter.
Infection control measures are also taught. Patients with COPD are at high risk for respiratory infections. They need to be taught the importance of annual influenza vaccine and the need for a pneumococcal pneumonia vaccine every 6 years. They need to avoid crowds and people, especially children, with respiratory infections.
ADHERENCE ISSUES
Health-care providers should be aware of the potential problem of nonadherence with the treatment regimen and should discuss the importance of adherence with the patient and family members.
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942
3827_Ch30_913-942 01/07/15 6:11 PM Page 942
943
CHAPTER 31
Teral Gerlt
PHYSIOLOGY OF THE NORMAL MENSTRUAL CYCLE, 943
PHARMACODYNAMICS, 945 Mechanism of Pregnancy Prevention
GOALS OF TREATMENT, 945 Safety
Tolerance
Effectiveness
RATIONAL DRUG SELECTION, 946 Guidelines
Cost
Patient Variables
Drug Variables
Dosing Regimens
Emergency Contraception
MONITORING, 954
OUTCOME EVALUATION, 954
C
PHYSIOLOGY OF THE NORMAL MENSTRUAL CYCLE
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944
Table 31–1 Contraceptive Options
Perfect Use Typical Use Method Advantages Disadvantages Efficacy Efficacy
3827_Ch31_943-956 01/07/15 6:09 PM Page 944
PHARMACODYNAMICS Mechanism of Pregnancy Prevention
GOALS OF TREATMENT
945
3827_Ch31_943-956 01/07/15 6:09 PM Page 945
Safety
Tolerance
Effectiveness
RATIONAL DRUG SELECTION
Guidelines
946
On The Horizon NEW OCS
In the last few years most of the research on new OCs has in- volved changing the type of estrogen and/or progestin in the formulations and the dosing pattern to decrease side effects and enhance ease of use (Sitruk-Ware, Nath, & Mishell, 2013). Natazia was released in 2010 and is the only four-phasic oral contracep- tive on the market. It is the first OC to contain estradiol valerate, a synthetic prodrug of 17ß-estradiol and a new progestin, dienogest, which displays properties of 19-nortestosterone derivatives as well as properties associated with progesterone derivatives.
The only chewable OC on the market, Generess, combines 0.8 mg norethindrone and 0.025 mg ethinyl estradiol with four 75 mg ferrous fumarate placebo tablets. The 24/4 regimen is intended to decrease breakthrough bleeding and provide short, light, predictable periods (Shrader & Dickerson, 2008).
A combination OC, Zoely, utilizing natural estrogen (17β estradiol), and a new progestin (nomegesterol acetate), manufactured by Merck have been approved in the United Kingdom and several European and Latin American coun- tries (Bahamondes & Bahamondes, 2014). The estrogen component, 17β estradiol, is structurally identical to endoge- nous 17β estradiol (Merck, 2014). Nomegesterol acetate has a 46-hour half-life, which increases efficacy (Merck, 2014). It has not received U.S. approval yet.
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947
Table 31–2 Oral Contraceptives
Brand Name Estrogen Dose (mcg) Progestin Dose (mg)
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948
Table 31–2 Oral Contraceptives—cont’d
Brand Name Estrogen Dose (mcg) Progestin Dose (mg)
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949
Table 31–2 Oral Contraceptives—cont’d
Brand Name Estrogen Dose (mcg) Progestin Dose (mg)
Cost
Patient Variables
Drug Variables Drug Interactions
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950
Table 31–3 WHO Contraindications to Initiation of Combined Contraception with 35 mcg EE or Less
Risk Contraindication
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Adverse Effects/Contraindications
Dosing Regimens Combined Contraceptives
951
CLINICAL PEARL
Multiphasic Pills Triphasic pill packs with pills of various colors may be confusing to some patients. If confusion is a concern, start with a monophasic OC for simple instructions.
Dosing Options
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Topical Patch
Vaginal Rings
952
Table 31–4 Instructions for Missed Oral Contraceptives
Missed 1 active pill
Missed 2–4 active pills
Missed 5 or more active pills
CLINICAL PEARL
LMP Notation Last menstrual period (LMP) should be considered a vital notation to be displayed at the top of each chart note in a female patient’s medical record.
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Progesterone-Only Contraceptives
953
3827_Ch31_943-956 01/07/15 6:09 PM Page 953
Emergency Contraception
MONITORING
954
CLINICAL PEARL
Depo-Provera and Osteoporosis Counsel patients using Depo-Provera to increase di- etary calcium intake and weight-bearing exercise. These interventions along with stopping smoking will mitigate bone mineral density changes.
CLINICAL PEARL
Emergency Contraception During each office visit, provide patients under 17 with an emergency contraception prescription and instruc- tions for use in case their primary contraception method fails.
OUTCOME EVALUATION
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955
CLINICAL PEARL
Report of Bleeding Patient reports of irregular or abnormal bleeding should be quantified with a menstrual calendar; have the pa- tient differentiate between days on which spotting oc- curs and days on which bleeding is as heavy as her menses. Keeping a count of sanitary napkins or tam- pons used per day of bleeding may help further quantify bleeding. Bleeding may be excessive if a patient is using tampons and pads together and experiencing bleeding accidents. Serial hematocrit measurement several days or a week apart may assist in evaluating excessive bleeding. Excessive bleeding should be evaluated for underlying etiology, such as uterine cancer or polyps, thyroid disorders, or bleeding dyscrasias (Hatcher et al, 2011).
PATIENT EDUCATION P ATIENT
EDUCATI ON
Overall Treatment Plan/Physiological Process
■■ Physiology of normal menstrual cycle.
■■ Need for follow-up visits: BP monitoring 3 months after initiation of methods containing estrogen, then annually. Breast and pelvic examinations, per national standards of care with client’s age, history, and risk factors taken into consideration.
■■ Breast self-awareness education.
■■ Safe-sex practices, including male or female condom use in conjunction with hormonal contraception for STI prevention.
■■ Emergency contraception access and use, which can be used with failures of all methods.
SPECIFIC TO THE DRUG THERAPY
■■ How contraceptives prevent pregnancy through suppression of ovulation in the hypothalamic-pituitary-ovarian axis or endometrial and cervical changes.
■■ Doses and schedules for taking the drug. Specifically start method, active versus inactive pills, when to expect menses, what to do if pills are missed, suggestions for optimizing compliance with dosing schedule.
■■ Anticipated menstrual changes because of method use, such as lighter or shorter menses, amenorrhea, or irregular bleeding patterns.
■■ Common side effects with method use, such as breakthrough bleeding in first few cycles of OC use, breast tenderness, nausea, possible weight changes.
■■ Serious side effects, their symptoms, and how to access care in an emergency.
■■ Interactions between hormonal contraception and other treatment modalities or lifestyle habits. Emphasize the dangers of smoking with combined hormonal contraception at any age and the increased risk in women over age 35. Also advise patients to stop combined hormonal contraception 4 weeks before and 2 weeks after major surgery to prevent thrombus formation.
■■ Review time frame for return to fertility after discontinuation for specific method.
REASONS FOR TAKING THE DRUG(S)
Hormonal contraception offers very high efficacy; this may be particularly important for women between 15 and 35 years of age when fertility is highest. Methods can be used for long- or short-term deferment of childbearing, allowing control over timing and spacing of pregnancies.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
■■ Women who use hormonal contraception may also enjoy noncontraceptive benefits, such as less menstrual discomfort or lighter flow and the ability to predict or manipulate timing of menses for vacation or other social events.
■■ Use of hormonal contraception also confers protection against uterine and ovarian cancer (Speroff & Darney, 2011).
Continued
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956
PATIENT EDUCATIONcont’d P ATIENT
EDUCATI ON
ADHERENCE ISSUES
■■ Access to clinic appointments and prescription refills is one of the reasons for gaps in OC use. If medically indicated, give the patient a full year of refills.
■■ Counseling, education, and use of written materials can increase a patient’s success with any method. Thorough patient education is the cornerstone of contraceptive success.
■■ The following are most important for patients taking OCs—they should take a pill every day in the correct order, and they should never just stop. If there are questions or concerns, they should always call the clinic first.
REFERENCES
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957
CHAPTER 32
Teri Moser Woo
DERMATITIS, 958 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
PSORIASIS, 966 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
ACNE AND ACNE ROSACEA, 969 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
SKIN INFECTIONS, 974 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
SKIN INFESTATIONS, 983 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
ALOPECIA ANDROGENETICA MALE PATTERN BALDNESS, 988 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
T
3827_Ch32_957-990 01/07/15 6:35 PM Page 957
DERMATITIS
Pathophysiology Eczema
Contact Dermatitis
Diaper Dermatitis
Seborrheic Dermatitis
958
3827_Ch32_957-990 01/07/15 6:35 PM Page 958
Goals of Treatment
Rational Drug Selection
Eczema
959
Table 32–1 Drugs Commonly Used: Dermatitis and Psoriasis
Drug Indication Strengths Available Dose Comments
Low Potency
Intermediate Potency
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960
Table 32–1 Drugs Commonly Used: Dermatitis and Psoriasis—cont’d
Drug Indication Strengths Available Dose Comments
High Potency
Super-High Potency
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961
Table 32–1 Drugs Commonly Used: Dermatitis and Psoriasis—cont’d
Drug Indication Strengths Available Dose Comments
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962
Table 32–1 Drugs Commonly Used: Dermatitis and Psoriasis—cont’d
Drug Indication Strengths Available Dose Comments
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963
Table 32–1 Drugs Commonly Used: Dermatitis and Psoriasis—cont’d
Drug Indication Strengths Available Dose Comments
3827_Ch32_957-990 01/07/15 6:35 PM Page 963
964
3827_Ch32_957-990 01/07/15 6:35 PM Page 964
Contact Dermatitis
Diaper Dermatitis
965
CLINICAL PEARL
Dermatitis • Occluding the surface with plastic wrap will increase
penetration of the topical corticosteroid. Do not do this in children, as it will increase the systemic ab- sorption of the steroid.
• For contact dermatitis, caution the patient using bath oils against slipping in the tub. Children should be su- pervised at all times when using bath dermatologi- cals, which can all cause the tub to be slippery. Older adults should also be monitored.
• For the patient with hand dermatitis, wearing cotton gloves overnight after applying a thick layer of emol- lient will increase absorption, and the patient will often see a significant improvement overnight.
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Seborrheic Dermatitis
Monitoring
Outcome Evaluation
Patient Education
PSORIASIS
Pathophysiology
Goals of Treatment
966
3827_Ch32_957-990 01/07/15 6:35 PM Page 966
967
PATIENT EDUCATION P ATIENT
EDUCATI ON
Dermatitis
RELATED TO THE OVERALL TREATMENT PLAN/DISEASE PROCESS
■■ Pathophysiology
■■ Role of preventive and nonpharmacological measures if appropriate
■■ Importance of adherence to the treatment regimen
■■ Self-monitoring of symptoms
■■ What to do when symptoms worsen
■■ Need for follow-up visits with the primary care provider
SPECIFIC TO THE DRUG THERAPY
■■ Reason for taking the drug and its anticipated action on the disease process
■■ Doses and schedules for taking the drug
■■ Possible adverse effects and what to do if they occur
■■ Interactions between other treatment modalities and these drugs
REASONS FOR TAKING THE DRUG(S)
■■ Patient education about specific drugs is provided in the appropriate chapter
SPECIFICALLY FOR ECZEMA
■■ Pathophysiology of eczema, that it is a chronic disorder requiring ongoing care, and that there is an itch-scratch-itch cycle that needs to be addressed, but that it is a recurring disease that can be controlled
■■ Avoidance of offending agents that cause exacerbations
■■ Appropriate use of topical corticosteroids should be demonstrated. With a sample, the provider can demonstrate how far a pea-sized amount of topical medication can be spread. The patient or caregiver applying the medication should be aware of the adverse effects of overuse of topical corticosteroids.
■■ Avoidance of irritants or agents that cause exacerbation of the eczema should be taught, with a written list of common ir- ritants provided to the patient
■■ Long-term therapy (skin hydration and emollient use) versus acute therapy
SPECIFICALLY FOR CONTACT DERMATITIS
■■ Pathophysiology
■■ Appropriate application of topical corticosteroids should be demonstrated
■■ Appropriate use of antipruritic medication
SPECIFICALLY FOR DIAPER DERMATITIS
■■ The parent or patient should be educated about the underlying pathophysiology of diaper dermatitis, in that it is usually an irritant dermatitis caused by chemical irritation from urine or feces, complicated by mechanical irritation of the diaper or undergarment rubbing and chafing the skin.
■■ Describing the characteristics of a secondary infection with Candida will assist with early identification and treatment of this common complication in diaper dermatitis.
■■ Nonpharmacological management such as sitz baths, air drying, and frequent diaper changes should be discussed.
■■ If properly treated, the skin should return to normal in the area in 3 to 4 days. If the patient is not responding to treatment in 48 hours, then a reevaluation is necessary.
SPECIFICALLY FOR SEBORRHEIC DERMATITIS
■■ The patient should know that seborrheic dermatitis cannot be cured and can only be controlled and that treatment will probably need to be continued long-term in adolescents and adults. In infants with cradle cap, it will usually resolve around age 6 months.
■■ The patient should contact the health-care provider if signs and symptoms of a secondary infection occur.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
■■ The total treatment regimen includes pharmacological and nonpharmacological measures. Be sure the patient and/or family members are aware of the specific measures to be taken.
ADHERENCE ISSUES
■■ Health-care providers should be aware of the potential problem of nonadherence and should discuss the importance of completing the entire treatment regimen with the patient and/or family members.
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Rational Drug Selection
968
CLINICAL PEARL
Psoriasis Psoriasis may affect a patient’s self-esteem and may exacerbate depression. The patient’s mood should be monitored. Referral to a support group or an organization such as the National Psoriasis Foundation (http://www .psoriasis.org) may be helpful.
Topical Therapy
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Phototherapy
Systemic Medications
Monitoring
Outcome Evaluation
Patient Education
ACNE AND ACNE ROSACEA
Pathophysiology
Goals of Treatment
969
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Rational Drug Selection
Topical Agents
970
Mild acne
No improvement
Benzoyl peroxide (OTC)
No improvement in 4–6 wk
Add oral antibiotic (tetracycline)
No improvement in 6–8 wk
No response in 6–8 wk
Positive response Treat as
moderate acne
Add topical: combined topical antibiotic
or retinoid
Topical: combined topical antibiotic product or topical retinoid plus
topical antibiotic
Moderate acne
Change antibiotic to minocycline
No improvement in 4–6 wk
No response: refer to dermatologist
Benzoyl peroxide (OTC)
Maintenance dose of oral or topical
antibiotics
Refer to dermatologist
Severe, nodular, or recalcitrant acne
Figure 32–1. Algorithm: Pharmacological management of acne.
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971
Table 32–2 Drugs Commonly Used: Acne
Drug Indication Strengths Available Dose Comments
Topical Retinoids
Topical Antibiotics
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972
Table 32–2 Drugs Commonly Used: Acne—cont’d
Drug Indication Strengths Available Dose Comments
Oral Antibiotics
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973
Table 32–2 Drugs Commonly Used: Acne—cont’d
Drug Indication Strengths Available Dose Comments
Oral Agents CLINICAL PEARL
Acne Tell patients using benzoyl peroxide products that ben- zoyl peroxide can bleach clothes and towels. Advise them to use an old or white pillowcase on their bed and an old or white towel to dry their hands after using these agents.
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Acne Rosacea
974
PATIENT EDUCATION P ATIENT
EDUCATI ON
Acne
RELATED TO THE OVERALL TREATMENT PLAN/DISEASE PROCESS
■■ Pathophysiology
■■ Role of preventive and nonpharmacological measures if appropriate
■■ Importance of adherence to the treatment regimen
■■ Self-monitoring of symptoms
■■ What to do when symptoms worsen
■■ Need for follow-up visits with the primary care provider
SPECIFIC TO THE DRUG THERAPY
■■ Reason for the drug’s being given and its anticipated action on the disease process
■■ Doses and schedules for taking the drug
■■ Possible adverse effects and what to do if they occur
■■ Interactions between other treatment modalities and these drugs
REASONS FOR TAKING THE DRUG(S)
■■ Patient education about specific drugs is provided in the appropriate chapter.
SPECIFICALLY FOR ACNE
■■ The patient should understand that it will take at least 6 weeks to determine if treatment is effective. Tying this into the explanation of normal skin growth will help the patient understand why it takes so long for the medication to work.
■■ Whatever level of treatment the patient is started on, the patient needs to understand what alternatives there are if the chosen treatment is not effective.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
■■ The total treatment regimen includes pharmacological and nonpharmacological measures. Be sure the patient and/or family members are aware of the specific measures to be taken.
ADHERENCE ISSUES
■■ Health-care providers should be aware of the potential problem of nonadherence and should discuss the importance of completing the entire treatment regimen with the patient and/or family members.
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975
Monitoring
Outcome Evaluation
Patient Education
SKIN INFECTIONS
Pathophysiology Bacterial Skin Infections
Viral Skin Infections
Fungal Skin Infections
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Goals of Treatment
Rational Drug Selection Bacterial Skin Infections
Viral Skin Infections
976
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977
Table 32–3 Drugs Commonly Used: Skin Infections
Drug Indication Strengths Available Dose Comments
Topical Antibiotics
Systemic Oral Antibiotics
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978
Table 32–3 Drugs Commonly Used: Skin Infections—cont’d
Drug Indication Strengths Available Dose Comments
Antivirals
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979
Table 32–3 Drugs Commonly Used: Skin Infections—cont’d
Drug Indication Strengths Available Dose Comments
Antifungals
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980
Table 32–3 Drugs Commonly Used: Skin Infections—cont’d
Drug Indication Strengths Available Dose Comments
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981
Table 32–3 Drugs Commonly Used: Skin Infections—cont’d
Drug Indication Strengths Available Dose Comments
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982
Table 32–3 Drugs Commonly Used: Skin Infections—cont’d
Drug Indication Strengths Available Dose Comments
Fungal Skin Infections
CLINICAL PEARL
Thrush Infants (and some older or very ill patients) are unable to hold nystatin suspension in their mouth. To achieve better results with nystatin administration, instruct the parents or caregivers to dip a clean cotton-tipped appli- cator into the nystatin solution, then rub the medication into the areas of thrush on the inner cheeks. Use a clean swab for each side and do not redip the applicator into the nystatin. After swabbing on the nystatin, the parent or caregiver can then administer 1 to 2 mL to each cheek.
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Monitoring
Outcome Evaluation
Patient Education
SKIN INFESTATIONS
Pathophysiology Lice
983
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984
PATIENT EDUCATION P ATIENT
EDUCATI ON
Skin Infections
RELATED TO THE OVERALL TREATMENT PLAN/DISEASE PROCESS
■■ Pathophysiology
■■ Role of preventive and nonpharmacological measures if appropriate
■■ Importance of adherence to the treatment regimen
■■ Self-monitoring of symptoms
■■ What to do when symptoms worsen
■■ Need for follow-up visits with the primary care provider
SPECIFIC TO THE DRUG THERAPY
■■ Reason for taking the drug and its anticipated action on the disease process
■■ Doses and schedules for taking the drug
■■ Possible adverse effects and what to do if they occur
■■ Interactions between other treatment modalities and these drugs
REASONS FOR TAKING THE DRUG(S)
■■ Patient education about specific drugs is provided in the appropriate chapter.
SPECIFICALLY FOR BACTERIAL SKIN INFECTIONS
■■ Explanation regarding the suspected cause of the infection and the rationale for the antibiotic treatment chosen
■■ Hand washing should be stressed to prevent spread of the skin infection to the patient or others.
■■ Give clear guidelines regarding notifying the practitioner if the infection is getting worse.
■■ Improvement should be noted in 24 to 48 hours; if not, a change in therapy may be indicated.
SPECIFICALLY FOR VIRAL INFECTIONS
Expectations of the medication. The healthy patient will have resolution of the vesicular lesions even without pharmacolog- ical intervention. Effective antiviral therapy decreases the time to scabbing and healing of lesions and decreases viral shed- ding time. In immunocompromised patients, the medication will help decrease the severity of the outbreak. ■■ Explain how the virus can become dormant and recur at a later time, even many years later.
■■ Patients using topical antivirals need to be instructed to use a glove or finger cot to apply the ointment to prevent getting the virus on their hands and spreading it; also, the patient may experience a transient burning when the medication is applied.
■■ It should be stressed to the patient and/or family members that the patient is contagious until the lesions are healed or scabbed over, even if antiviral agents are being taken; the patient should avoid contact with immunocompromised indi- viduals and avoid sexual intercourse if the patient has genital herpes lesions.
SPECIFICALLY FOR FUNGAL INFECTIONS
■■ The patient and/or family members should understand how the fungal infection is spread and how contagious the infection is.
■■ Family members and pets should be checked for signs of infection and treated if indicated.
■■ The provider should stress the possibility of relapse if the medication regimen is not followed correctly and for the full treatment time.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
■■ The total treatment regimen includes pharmacological and nonpharmacological measures. Be sure the patient and/or family members are aware of the specific measures to be taken.
ADHERENCE ISSUES
■■ Health-care providers should be aware of the potential problem of nonadherence and should discuss the importance of completing the entire treatment regimen with the patient and/or family members.
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Scabies
Goals of Treatment
Rational Drug Selection
Head Lice
985
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Body Lice
Pubic Lice
986
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Scabies
Monitoring
Outcome Evaluation
Patient Education
987
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ALOPECIA ANDROGENETICA (MALE PATTERN BALDNESS)
Pathophysiology
Goals of Treatment
Rational Drug Selection
Minoxidil
Finasteride
Monitoring
988
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Outcome Evaluation
Patient Education
REFERENCES
989
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991
CHAPTER 33
Kathy Shaw • Marylou Robinson
PATHOPHYSIOLOGY, 992 Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Complications
Prediabetes
Diagnosis and Screening
PHARMACODYNAMICS, 997 General Diabetes Management and Glycemic Control
Insulin
Oral Agents
Other Injectable Drugs
GOALS OF TREATMENT, 1000
APPROPRIATE TREATMENT, 1001 Initial Assessment
Setting a Glycemic Target
Lifestyle Modifications
Pharmacologic Management
PREVENTION AND MANAGEMENT OF COMPLICATIONS IN DIABETES, 1010 Obesity
Coronary Heart Disease and Heart Failure
Hyperlipidemia
Hypertension
Nephropathy
Neuropathy
Retinopathy
Thyroid Function
Autoimmune Disorders
ASSESSING GLYCEMIC CONTROL, 1016 Hb A1c
Self-Monitoring of Blood Glucose (SMBG)
OUTCOME EVALUATION, 1017
PATIENT EDUCATION, 1017
D
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PATHOPHYSIOLOGY
Type 1 Diabetes Mellitus
992
Table 33–1 Comparison of Type 1 and Type 2 Diabetes Mellitus
Characteristic Type 1 Type 2
3827_Ch33_991-1020 01/07/15 2:46 PM Page 992
Type 2 Diabetes Mellitus
993
On The Horizon CURE FOR TYPE I DM?
Two recent research endeavors are exploring the use of older non-diabetic medications to intervene in early cases of DM I. Mice given verapamil essentially eradicated a protein that causes the death of beta cells. Trials funded by the Juvenile Diabetes Foundation with humans are planned to test this “cure” of type 1 DM (Shalev, 2014). Other researchers at Massachusetts General are exploring an interesting positive effect on pancreas recovery after administration of the old BCG vaccine originally developed to assist with TB care (Faustman et al, 2012).
3827_Ch33_991-1020 01/07/15 2:46 PM Page 993
994
Polyuria InfectionsGlycosuria Dilutional hypo-NA+
Hyperglycemia
No insulin
HLA DR3/5 viral exposure beta cell destruction
Cardiac dysrhythmia
Decreased O2 trans
Intracellular dehydration
Intracellular starvation
Altered protein metabolism
Altered fat metabolism
AcidosisRenal threshold exceeded
Hyper-K+ Circulatory overload
Polydipsia Weight loss
Polyphagia Poor wound healing
Impaired immune system
Figure 33–1. Pathophysiology of type 1 diabetes.
3827_Ch33_991-1020 01/07/15 2:46 PM Page 994
Complications
Pre-Diabetes
Diagnosis and Screening Diagnostic Criteria for Diabetes and Pre-Diabetes
995
Table 33–2 Diagnostic Criteria for Diabetes Mellitus and Pre-Diabetes
Diagnostic Category Diagnostic Criteria
Diabetes mellitus
Pre-diabetes
3827_Ch33_991-1020 01/07/15 2:46 PM Page 995
Diagnostic Criteria for Pregnant Women
Screening Criteria for Children
996
Table 33–3 Criteria for Testing Asymptomatic Adults for Diabetes
3827_Ch33_991-1020 01/07/15 2:46 PM Page 996
PHARMACODYNAMICS
General Diabetes Management and Glycemic Control
Insulin
997
Table 33–4 Common Insulin Types, Onset, Peak, and Duration
Type Insulin Onset Peak Duration
Rapid-Acting
Short-Acting
Intermediate-Acting
Long-Acting
Fixed Combination
3827_Ch33_991-1020 01/07/15 2:46 PM Page 997
Oral Agents
Biguanides
998
On The Horizon ULTRA-LONG-ACTING INSULIN
An ultra-long-acting basal insulin analogue, insulin degludec, has just been approved. Duration of action nears 42 hours, so it might have an irregular dosing schedule. It is thought to have lower rates of nocturnal hypoglycemia compared to glargine. Its higher cost will be an issue. There are concerns about adverse CV effects.
CLINICAL PEARL
Rules for Fine-Tuning Insulin Doses • The correction factor (CF) and insulin: carbohydrate ratio
(I:C) for patients with either type 1 or 2 taking insulin. • The rule of 1,500 enables the provider to find the CF
or how much 1 unit of insulin will drop blood sugar for high blood glucose levels (usually greater than 140 to 150). First, calculate the total daily dose (TDD) of insulin as basal + bolus—about 50% of each. Then divide 1,500 by the TDD. For example, 1,500 divided by 30 units per day of insulin equals 50. One unit of rapid-acting insulin will drop glucose 50 points.
• The rule of 500 enables the provider to find the I:C ratio. Divide 500 by TDD. For example, 500 divided by 30 units per day of insulin equals 16.7. One unit will cover 16 to 17 g of carbohydrate (CHO). For ease of use, round down to 1 unit:15 g.
3827_Ch33_991-1020 01/07/15 2:46 PM Page 998
Sulfonylureas
Alpha-Glucosidase Inhibitors
Thiazolidinediones
Meglitinides
Selective Sodium Glucose Co-transporter 2 (SGLT-2)
999
3827_Ch33_991-1020 01/07/15 2:46 PM Page 999
Incretin Therapy
Dipeptidyl Peptidase-4 Inhibitors
Glucagon-Like Peptide-1 Receptor Agonists (GLP-1s)
Other Injectable Drugs
GOALS OF TREATMENT
1000
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1000
APPROPRIATE TREATMENT
Initial Assessment
Setting a Glycemic Target
1001
Table 33–5 American Diabetes Association Treatment Targets for Persons With Diabetes
Hb A1c
Preprandial Plasma Glucose
2-hour Postprandial Plasma Glucose
Blood Pressure
LDL
Triglycerides
HDL
Excess Urinary Albumin Excretion
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1001
Lifestyle Modifications
1002
Table 33–6 Correlation Between Hb A1c Level and Mean Plasma Glucose Level
Hemoglobin A1c Levels Mean Plasma Glucose (mg/dL)
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Immunizations
1003
Table 33–7 Lifestyle Modifications for Patients With Diabetes
Nutrition
Exercise
Weight Loss
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Considerations in Special Populations
1004
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Race and Ethnic Groups
1005
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Pharmacological Management
Type 1 Diabetes
1006
Table 33–8 Basal Bolus Insulin
Rapid-Acting (RAI) Short-Acting (SAI) Intermediate-Acting (IAI) Long-Acting (LAI) Mix
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1007
Establish glycemic target
Adults without severe complications who are willing and able to use individualized algorithm, take up to 4 injections/day and test BG at least 4!/day. Tight control/intensive therapy: —FPG and premeal 90–130 mg/dL —Postprandial <180 mg/dL —HbA1c <7%
Children Plasma blood glucose goal (mg/dL)
Patients who are at high risk for hypoglycemia; older adults; patients w/ late disease or advanced, severe complications; not motivated to follow complex regimen. Conventional therapy: —FPG 120–150 mg/dL —Bedtime glucose 120–160 mg/dL —HbA1c 7%–8%
Age 0–6 7–12 13–19
Before meals 100–180 90–180 90–130
Bedtime 110–200 100–180 90–150
HbA1c 7.5%–8.5% <8% <7.5%
Lifestyle modifications (see Table 33-7) Plus insulin
1. Start w/ total daily dose 0.2–0.4 units/kg; usual 0.4–0.8 units/kg 2. 50% basal give once or twice daily (glargine, detemir preferred, or NPH) 3. 50% prandial—rapid acting preferred (aspart, lispro, glulisine, or R) a. Start with 1 unit/15 g carbohydrate OR b. Divide into equal doses if consistent carbohydrate OR c. Divide into 3 doses based on meal size 4. Correction dosing to be used in addition to meal dose for blood sugars >150 More advanced methods may be used as patient comfort increases. See text.
Hypoglycemia (<70) Treat before addressing hyperglycemia —Fasting: decrease basal dose —Preprandial: decrease dose of rapid acting at preceding meal
Hyperglycemia —Fasting: >130 increase long-acting dose —Preprandial: >150 increase dose at previous meal —Titrate both q 3 days
Contact by e-mail or phone 1–2!/wk initially by NP, RN, or CDE
FU visit at 1 month —Review blood sugar patterns, activity, hypoglycemic episodes —Continue dose adjustment as needed
Contact as needed by NP, RN, or CDE
FU visit at 3 mo —Review as above —HbA1c
Glycemic targets met? NoYes
—Continue regimen —May advance to pump therapy or advanced carbohydrate counting. See Clinical Pearls.
—Review lifestyle, insulin regimen, and adherence —Consider confounding variables —Adjust insulin based on patterns
HbA1c and visit every 3 mo
Most Type 1 patients should be followed by a multidisciplinary endocrinology team.
Figure 33–2. Treatment algorithm for type 1 diabetes.
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1008
CLINICAL PEARL
Type I Diabetes Treatment • Most patients should see an endocrinologist and di-
abetes treatment team; treatment can be challenging and a team approach works best. Consultation with a Certified Diabetes Educator is a must.
• Make small changes gradually with close follow-up (every 1 to 2 wk) until adequate control is achieved.
• Ongoing follow-up has been shown to be very bene- ficial; this can be done by phone or electronically.
• It is normal to have wide variability in BGL even with adherence to the treatment plan. Variability does not necessarily mean nonadherence.
• Consistency in mealtimes, injection sites, and timing and frequency of exercise is vital.
• The treatment plan must be individualized with adjustments preplanned for anticipated sudden increases in physical activity such as summer sports camps or ski vacations.
Type 2 Diabetes
Table 33–9 ! Commonly Used Insulin Regimens
Insulin Therapy Type Insulin Schedule Advantages Disadvantages
Intensive Insulin Therapy
Split-Mix Insulin Therapy—3 injections
Split-Mix Insulin Therapy—2 injections
Basal = IAI
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1009
a. Consider beginning at this stage in patients with very high HbA1c (e.g., > 9%). b. Consider rapid-acting, nonsulfonylurea secretagogues (meglitinides) in patients with irregular meal schedules or who develop late postprandial hypoglycemia on sulfonylureas. c. See (…)[text] for additional potential adverse effects and risks(…). d. Usually a basal insulin (NPH, glargine, detemir) in combination with noninsulin agents e. Certain noninsulin agents may be continued with insulin (see text).. Consider beginning at this stage if patient presents with severe hyperglycemia (>16.7–19.4 mmol/L [300–350 mg/dL]; Hb A1c >10.0–12.0%) with or without catabolic features (weight loss, ketosis, etc.).
Figure 33–3. General recommendations for antihyperglycemic therapy in type 2 diabetes. Inzucchi et al (2012). Management of hyperglycemia in type 2 diabetes: A patient centered approach. Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care, 35(6), 1364–1379.
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Severe Insulin Resistance Therapy: U-500 Insulin
PREVENTION AND MANAGEMENT OF COMPLICATIONS IN DIABETES
Obesity
1010
On The Horizon U-300 INSULIN
The FDA has just approved a U-300 insulin (Toujeo), which is a long-acting basal insulin with a lower glucose lowering effect per unit than glargine, but lower risks of hypoglycemia. Lower- volume injections will be beneficial. The precautions about mixing solutions in a syringe also pertain. This insulin uses units per dose like glargine; this is unlike the U-500 insulins, which are volume based.
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Coronary Artery Disease and Heart Failure
Hyperlipidemia
1011
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1012
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Hypertension
1013
On The Horizon RENAL INSUFFICIENCY
Metformin and other medications are curtailed when creati- nine values rise. Several recent calls to continue with drug use if monitoring for lactic acidosis is not yet FDA-approved.
Nephropathy
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Neuropathy
1014
Table 33–10 Major Clinical Manifestations of Diabetic Autonomic Neuropathy
Body System Manifestations
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Retinopathy
1015
CLINICAL PEARL
Pumps and Daylight Savings Time Some pumps may not automatically adjust for changes in daylight savings time. This will not impact basal in- sulin rates, but bolus doses can be impacted. Time-zone travel can also impact timing of doses if the pump is not GPS-enabled.
Thyroid Function
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Autoimmune Disorders
ASSESSMENT OF GLYCEMIC CONTROL
Hb A1c
Self-Monitoring of Blood Glucose (SMBG)
1016
Table 33–11 Situations Where Hb A1c May Be Unreliable
Disease or Impact on Situation Hb A1c Value
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OUTCOME EVALUATION PATIENT EDUCATION
1017
DIABETES MELLITUS P ATIENT
EDUCATI ON
Related to the Overall Treatment Plan/Disease Process
■■ Pathophysiology of diabetes and the long-term effects of inadequate management on target organs
■■ Role of lifestyle modification, especially dietary therapy, in improving outcomes and keeping the number and cost of required drugs down
■■ Importance of adherence to the treatment regimen
■■ Need for regular follow-up visits with the primary care provider and other specialists
SPECIFIC TO THE DRUG THERAPY
■■ Reason for taking the drug(s) and the anticipated action of the drug(s) on the disease process
■■ Doses and schedules for taking the drugs
■■ Possible adverse reactions (especially hypoglycemia, DKA, and hyperosmolar hyperglycemic non-ketotic coma), how to prevent them, and what to do if they occur
■■ Interactions between lifestyle modifications and these drugs
REASONS FOR TAKING THE DRUG(S)
Patient education about specific drugs is provided in Chapter 21. Specific information related to diabetes includes the following: glycemic control and management of hypertension and hyperlipidemia are central to reducing morbidity and mortality from cardiovascular disease and preventing retinopathy and end-stage renal disease. The risks of these complications while maintaining the potential for a good quality of life with appropriate treatment must be discussed.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
Expectations should be clear about what the drugs can and cannot do. Dietary and other lifestyle modifications comple- ment drug therapy and are equally important. Diabetes is a chronic, progressive disease. Self-management requires incor- porating a combination of medications, healthy eating, exercise, stress management, and SMBG into the everyday life of the patient with diabetes.
ADHERENCE ISSUES
Nonadherence to the treatment regimen may result in increased risk for complications and reduced life expectancy. Health- care providers should be aware of potential problems with nonadherence, discuss the importance of adherence at each follow-up visit, and assist patients in removing barriers to adherence such as lack of social support and cost of the treat- ment regimen. A team approach with the patient as an active partner should be maximized. Ways to deal with nonadher- ence are discussed in Chapter 6. Patient education booklets are available from the ADA, which can be accessed on the Internet at www.diabetes.org.
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REFERENCES
1018
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1018
1019
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1021
CHAPTER 34
Teri Moser Woo
GASTROESOPHAGEAL REFLUX DISEASE, 1021 Pathophysiology
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
PEPTIC ULCER DISEASE, 1028 Pathophysiology
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
P
GASTROESOPHAGEAL REFLUX DISEASE
Pathophysiology
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Signs and Symptoms
1022
Table 34–1 Foods and Drugs That Influence GERD
Foods and Drugs Action on LES Tone
Foods
Drugs
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Diagnosis
Pharmacodynamics
Drugs to Improve Lower Esophageal Sphincter Tone
Drugs to Reduce the Amount of Acid
1023
Table 34–2 Signs and Symptoms of GERD and Potential Complications
Signs and Potential Suggestive of Symptoms Common Unusual Extra-esophageal Complication Cancer (Alarm)
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Drugs to Improve Peristalsis
Drugs to Decrease Mucosal Exposure
1024
K+
Parietal cell with proton pump
Antibiotic Antacid
+ HCL water + salt
Parietal cell with H2-receptor
Acid secretion
Ulcer with H. pylori
Proton pump inhibitors bind to the enzyme H+, K+-ATPase and prevent
acid from being secreted.
Antibiotics eradicate H. pylori, the primary cause of peptic ulcers.
Alkaline antacids chemically combine with acids to lower stomach pH.
H2-receptor antagonists occupy the histamine receptors and
prevent acid secretions.
Proton pump
Proton pump inhibitors
H2-receptor
H2-receptor blockers
Figure 34–1. Sites of action of drugs used to treat GERD and PUD.
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1024
Goals of Treatment
Rational Drug Selection Algorithm
Lifestyle Modifications
Drug Therapy
Patient Variables
1025
Dyspepsia or mild GERD symptoms
No erosive disease
OTC antacids or H2RAs to control
symptoms
Moderate to severe GERD or erosive
disease
Lifestyle modification and proton pump inhibitors (PPI) Continue therapy for 8 weeks
Reassess every 6–12 months. Consider referral to
gastroenterology specialist.
Symptoms Relieved Wean off PPI.
Erosive esophagitis or Barrett's esophagitis
NO response to PPI
Symptoms recur.
Restart PPI.
Continue on PPI.
Refer to Gl specialist.
Figure 34–2. Algorithm for gastro - esophageal reflux disease (GERD).
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1026
BOX 34–1 LIFESTYLE MODIFICATIONS IN GERD MANAGEMENT FOR ADULTS
Antireflux Maneuvers
• Sleep with the head of the bed elevated 6 to 8 inches with bed blocks or wedges or by using a hospital bed.
• Avoid the recumbent position within 3 hours after eating.
• Avoid bending over within 3 hours after eating. • Avoid exercise, especially strenuous exercise,
within 3 hours after eating. • Attain and maintain appropriate body weight.
DIETARY CONSIDERATIONS
• Avoid spicy, acidic, tomato-based, or fatty foods. • Avoid chocolate, peppermint, onions, and citrus
fruits and juices. • Limit your intake of coffee, tea, alcohol, and
colas. • Eat moderate amounts of food at each meal. Do
not gorge yourself. • Avoid eating meals or bedtime snacks within
3 hours of going to bed. • Reserve fluid intake for after or between meals.
SMOKING CESSATION
• Stop smoking. Smoking both lowers LES tone and increases the secretion of gastric acid.
• Smoking cessation is a high priority.
WEIGHT LOSS
• Weight loss may improve symptoms
Table 34–3 Lifestyle Modifications in GERD Management for Infants and Children
Antireflux Maneuvers Dietary Considerations
Infants
Children
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Monitoring
1027
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1027
Outcome Evaluation
Patient Education
PEPTIC ULCER DISEASE
Pathophysiology
Gastric Ulcer Disease
1028
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1028
1029
PATIENT EDUCATION P ATIENT
EDUCATI ON
Gastroesophageal Reflux Disease
RELATED TO THE OVERALL TREATMENT PLAN/DISEASE PROCESS
■■ Pathophysiology of gastroesophageal reflux and its long-term risks for permanent esophageal damage and cancer of the esophagus
■■ Central role of lifestyle modifications in improving prognosis and keeping the number and cost of required drugs down
■■ Importance of adherence to the treatment regimen
■■ Need for follow-up visits with the primary care provider if the symptoms do not resolve or if they recur
SPECIFIC TO THE DRUG THERAPY
■■ Reason for the drug(s) being given and the anticipated action of the drug(s) on the disease process
■■ Doses and schedules for taking the drug(s)
■■ Possible adverse reactions and what to do when they occur
■■ Coping mechanisms for complex and costly drug regimens
■■ Interaction between lifestyle modifications and these drugs
REASONS FOR TAKING THE DRUG(S)
Patient education about specific drugs is provided in Chapter 20. Specific information related to GERD: drugs used to treat GERD are given to reduce symptoms, heal any esophageal ulcers, reduce the risk for permanent esophageal damage or cancer, and prevent relapse of symptoms. Different drugs have different roles with each of these. The expectations should be clear about what the drugs can and cannot do. Drugs alone will not correct the disorder.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
Lifestyle modification is equally important in disease management. GERD is a chronic condition. Patients with GERD must understand the lifelong nature of the disorder and the need to incorporate the treatment regimen into their everyday lives.
ADHERENCE ISSUES
Any disease process where lifestyle modifications are central to management is prone to problems with adherence. Health- care providers should be aware of the potential problem of nonadherence, discuss the importance of adherence at each follow-up visit, and assist patients in removing barriers to adherence, such as the complexity and cost of the treatment regimen and the presence of adverse reactions.
Table 34–4 Comparison of Gastric and Duodenal Ulcer Disease
Characteristic Gastric Ulcer Duodenal Ulcer
Pathophysiology
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Duodenal Ulcer Disease
Diagnosis
Pharmacodynamics
Goals of Treatment
Rational Drug Selection Algorithm
1030
BOX 34–2 SUBSTANCES THAT CAN DISRUPT THE GASTRIC MUCOSAL BARRIER
Drugs
Alcohol Aspirin Caffeine Corticosteroids NSAIDs Tobacco
Other Causes
H. pylori infection Bile and pancreatic secretions Physiological and psychological stress Salmonella Spicy, irritating foods* Staphylococcus organisms Uremia associated with renal failure
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1031
Step 1 Lifestyle modification and antacids
Refer to gastroenterologist for endoscopy.
PPI Continue for 8–12 weeks
until healing complete. Repeat endoscopy
in 12 weeks to determine healing.
Complicated (bleeding)
High risk* Consider chronic suppressive
therapy with PPI or H2RA. (*smokers, !60 yr, COPD, CAD,
hx of bleeding or perforated ulcer, patients on NSAIDs)
Step 2 H. pylori testing and
proton pump inhibitor (PPI)
Step 3 Treatment for H. pylori with
antibiotics and PPI
Low risk No ongoing
therapy
Treatment for H. pylori
Uncomplicated
Figure 34–3. Stepped-approach algo- rithm for peptic ulcer disease.
Table 34–5 Invasive and Noninvasive Diagnostic Tests for
Test Sensitivity Specificity Comments
Noninvasive
Invasive
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Lifestyle Modifications
Drug Therapy
Adverse Drug Reactions for the Total Regimen
Antimicrobial Resistance
1032
Table 34–6 ! Drug Treatment Protocols for Eradication
Drug 1 Drug 2 Drug 3 Drug 4 Comments
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Patient Variables
Monitoring
Outcome Evaluation
1033
PATIENT EDUCATION PA TIENT
EDUCATI ON
Peptic Ulcer Disease
RELATED TO THE OVERALL TREATMENT PLAN/DISEASE PROCESS
■■ Understanding the pathophysiology of ulcer forma- tion and its long-term risks for bleeding and cancer of the stomach
■■ Role of lifestyle modifications in total treatment regimen
■■ Importance of adherence to the treatment regimen, especially in light of antimicrobial resistance
■■ Need for follow-up visits with the primary care provider if the symptoms recur or do not resolve
SPECIFIC TO THE DRUG THERAPY
■■ Reason for the drug(s) being given and the antici- pated action of the drug(s) on the disease process
■■ Doses and schedules for taking the drug(s)
■■ Possible adverse reactions and what to do when they occur
■■ Coping mechanisms for complex and costly drug regimens
■■ Interactions between lifestyle modifications and these drugs
REASONS FOR TAKING THE DRUG(S)
Patient education about specific drugs is provided in Chapters 20 and 24. Specific information related to PUD includes the following: drugs used to treat PUD are given to treat H. pylori, reduce symptoms, heal any ul- cers, reduce the risk for complications, and prevent re- lapse of symptoms. Different drugs have different roles with each of these.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
Lifestyle modification is important in disease manage- ment. PUD is often a chronic condition, requiring lifelong maintenance therapy.
ADHERENCE ISSUES
Any disease process in which lifestyle modifications are required or in which a complex regimen of three or four drugs over a period of weeks is required is likely to have problems with adherence. Health-care providers should be aware of the potential problem of nonadherence, discuss the importance of adherence, and assist pa- tients in removing barriers to adherence, such as the complexity and cost of the treatment regimen and the presence of adverse reactions.
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Patient Education
REFERENCES
1034
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1035
CHAPTER 35
Theresa Mallick-Searle
MIGRAINE, 1036 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
TENSIONTYPE HEADACHES, 1053 Pathophysiology
Goals of Therapy
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
CHRONIC DAILY HEADACHES, 1054 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
CLUSTER HEADACHES, 1056 Pathophysiology
Goals of Treatment
Rational Drug Therapy
Monitoring
Outcome Evaluation
Patient Education
MEDICATIONOVERUSE HEADACHES, 1057 Pathophysiology
Goals of Therapy
Rational Drug Therapy
Monitoring
Outcome Evaluation
Patient Education
POSTTRAUMATIC POSTCONCUSSIVE HEADACHES, 1058 Pathophysiology
Goals of Therapy
Rational Drug Therapy
Monitoring
Patient Education
H
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MIGRAINE
Pathophysiology
Goals of Treatment
Rational Drug Selection
Acute Therapy
1036
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1037
Table 35–1 Common Migraine Triggers
Factor Triggers
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1038
Yes
No
Yes
Yes
No
Yes
No
No
Patient has a migraine
Determine severity
Early and mild (0–4 h)
Simple analgesics (OTC “headache” preparation,
aspirin, ibuprofen, naproxen sodium)
Nonpharmacologic measures (darkened room,
lying down, ice to head)
Moderate to severe (0–4 h)
Ultrasevere or lasting >72 h
Antiemetic, if needed for nausea (metoclopramide)
Unresponsive to treatment
Treat as per moderate or severe
Simple analgesics plus antiemetic or analgesic/opioid
combination
Coronary artery disease or uncontrolled hypertension?
Pregnant? Taking MAOIs or SSRIs?
DHE given IM or IV
Headache pain accompanied by nausea/vomiting?
Ergotamine suppository plus antiemetic or sumatriptan SC
or nasal spray or DHE nasal spray
Oral triptan or ergotamine suppository
Limit use of any medication to 2 to 3 times per week
Poor response? Unacceptable adverse effects?
Recurrence of migraine after use?
Switch to another drug
New drug effective?
Reevaluate treatment
Combination drug (if indicated) (Midrin or butalbital-containing drug)
(use with caution)
Figure 35–1. Treatment algorithm for acute migraine headache.
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1039
Table 35–2 Drugs Commonly Used: Headaches
Strengths Rebound Drug Initial Dose Maximum Dose Available Potential Comments
Nonnarcotic Analgesics
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1040
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound Drug Initial Dose Maximum Dose Available Potential Comments
Combination Analgesics
Narcotic Analgesics
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1041
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound Drug Initial Dose Maximum Dose Available Potential Comments
Ergot Derivatives
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1042
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound Drug Initial Dose Maximum Dose Available Potential Comments
Serotonin Receptor Agonists
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1043
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound Drug Initial Dose Maximum Dose Available Potential Comments
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1044
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound Drug Initial Dose Maximum Dose Available Potential Comments
Alpha Agonist, Central
Antiemetics
Beta Blockers
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1045
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound Drug Initial Dose Maximum Dose Available Potential Comments
Tricyclic Antidepressants
Anticonvulsants
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1046
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound Drug Initial Dose Maximum Dose Available Potential Comments
NSAIDs
Calcium Channel Blockers
Serotonin Antagonist
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1047
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound Drug Initial Dose Maximum Dose Available Potential Comments
Antispasmodic/Neurotoxin (inhibits acetylcholin release from nerve endings)
Nutraceuticals
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1048
CLINICAL PEARL
Ergotamine Suppositories Ergotamine suppositories can provide relief if taken at the beginning of a migraine attack. If a patient has not used ergotamine before, instruct the patient to use one-third of a 2 mg suppository initially and repeat in 30 to 60 minutes. Refrigeration makes the suppository easier to slice.
CLINICAL PEARL
Triptans It is advisable to administer the first dose of any of the triptans under direct supervision to monitor for unrec- ognized coronary disease. The patient should receive the first dose in the clinic (or urgent care center) and be monitored for any adverse cardiovascular effects. Sumatriptan is effective in decreasing the severity of headache in 54% to 80% of patients.
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Preventive Therapy
1049
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1050
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Nonpharmacological Management of Migraine
1051
On The Horizon MIGRAINES
A number of medications are in the pipeline for treatment of migraines. An inhaled form of dihydroergotamine (Semprana) will be reviewed by the FDA in 2015. Two monoclonal antibody preparations that target calcitonin gene-related peptide (CGRP) are in experimental trials. CGRP is a protein that is thought to trigger migraines. ALD403 (Alder Biopharmaceuticals) and LY2951742 (Lilly) have both demonstrated reduction in migraines com- pared to placebo. Boehringer Ingelheim Pharmaceuticals’ olcegepant, a CGRP antagonist, is undergoing phase II trials in Europe.
Monitoring
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1051
Outcome Evaluation
Patient Education
1052
PATIENT EDUCATION PA TIENT
EDUCATI ON
Headaches
RELATED TO THE OVERALL TREATMENT PLAN/DISEASE PROCESS
■■ Pathophysiology of headache
■■ Role of lifestyle modifications
■■ Importance of adherence to the treatment regimen
■■ Self-monitoring of symptoms and associated symptoms
■■ What to do when symptoms and associated symptoms worsen
■■ Need for regular follow-up visits with the primary care provider
SPECIFIC TO THE DRUG THERAPY
■■ Reason for taking the drug and its anticipated action in the disease process
■■ Doses (including maximum dosage) and schedules for taking the drug
■■ Possible adverse effects and what to do if they occur
■■ Interactions between other treatment modalities and these drugs
■■ Potential for medication-overuse headache
REASONS FOR TAKING THE DRUG(S)
Patient education about specific drugs is provided in the appropriate chapters. Specific reasons for taking the drug(s) should be discussed on an individual basis, depending on the diagnosis and nature of the headache. Medication overuse should also be discussed at the beginning of treatment.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
The total treatment regimen includes pharmacologi- cal and nonpharmacological measures, as well as the headache diary. A realistic expectation and goals of the individualized treatment plan should be presented.
ADHERENCE ISSUES
Nonadherence with the treatment regimen may affect functional status. Health-care providers should be aware of the potential problem of nonadherence and discuss the importance of adherence with the patient and family.
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1052
TENSION-TYPE HEADACHES
Pathophysiology
Goals of Therapy
Rational Drug Selection
Acute Therapy
1053
BOX 35–1 HEADACHE RESOURCES FOR PATIENTS AND HEALTH-CARE PROVIDERS
American Headache Society
http://www.americanheadachesociety.org
The American Headache Society (AHS) is a professional society of health-care providers dedicated to the study and treatment of headache and face pain. Founded in 1959, AHS brings together physicians and other health- care providers from various fields and specialties to share concepts and developments about headache and related conditions.
American Council for Headache Education
http://www.achenet.org
This site is geared for patients and is connected with the American Headache Society. There is patient information on headaches in general, migraines, and prevention and treatment of headaches, as well as a discussion forum for patients. There are specific sections for children and women.
National Headache Foundation
www.headaches.org
Nonprofit organization dedicated to educating headache sufferers and health-care professionals about headache causes and treatments.
International Headache Society
www.ihs-headache.org
The International Headache Society (IHS) is an interna- tional professional organization working with others for the benefit of people affected by headache disorders. The purpose of IHS is to advance headache science, education, and management, and to promote headache awareness worldwide. Note: The Web site asks about membership but nonmembers can access all guidelines.
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1053
Preventive Therapy
Monitoring
Outcome Evaluation
Patient Education
CHRONIC DAILY HEADACHES
1054
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1054
Pathophysiology
Goals of Treatment
Rational Drug Selection Chronic Migraine
Hemicrania Continua
Monitoring
Outcome Evaluation
Patient Education
1055
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1055
CLUSTER HEADACHES
Pathophysiology
Goals of Treatment
Rational Drug Therapy
Acute Therapy
Preventive Therapy
Monitoring
Outcome Evaluation
1056
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1056
Patient Education
MEDICATION-OVERUSE HEADACHES
Pathophysiology
Goals of Therapy
Rational Drug Therapy
1057
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1057
Monitoring
Outcome Evaluation
Patient Education
POST-TRAUMATIC (POST- CONCUSSIVE) HEADACHES
Pathophysiology
1058
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1058
Goals of Therapy
Rational Drug Therapy
1059
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1059
Monitoring
Patient Education
1060
On The Horizon
DRUGS THAT MAY PROVIDE NEUROPROTECTION FOR TBI
Magnesium has demonstrated neuroprotective properties in nu- merous TBI models. Magnesium has been shown to have many beneficial effects, including noncompetitive NMDA receptor blockade, inhibition of presynaptic excitatory neurotransmitter release, blockade of voltage-gated calcium channels, and reduc- tion in inflammatory cascades (Burd, Breen, Friedman, Cha, & Elovitz, 2010). Unfortunately, the data are lacking in specific and safe recommendations for the use of magnesium in this popula- tion. Additional studies should help clarify the clinical utility of magnesium supplementation following TBI (Maas & Murray, 2007).
Progesterone is an agent that appears to provide neuro- protection by multiple mechanisms. After TBI, progesterone has been shown to decrease oxidative stress by reducing membrane lipid peroxidation, reduce BBB disruption, and ameliorate the brain’s inflammatory response. A phase III clini- cal trial, the Progesterone for the Treatment of Traumatic Brain Injury (ProTECT III), is currently underway to further assess the clinical efficacy of progesterone (Vink & Nimmo, 2009).
Erythropoietin has been identified as a neuroprotective agent that appears to ameliorate TBI by multiple avenues. The Erythropoietin in Traumatic Brain Injury (EPO-TBI) trial is currently underway to assess whether erythropoietin can improve neuro- logical outcome in severe TBI patients (Vink & Nimmo, 2009).
Minocycline has been extensively studied in mice and has been shown to be an effective antioxidant and attenuator of the inflammatory sequelae of TBI. The study, A Safety and Feasibility of Minocycline in the Treatment of Traumatic Brain Injury, is currently underway, which will likely lead to additional clinical investigation of this drug (Schouten, 2007).
Cyclosporin is another multifactorial compound that has neuroprotective effects, including improving mitochondrial functioning, blocking free radical production, and inhibiting calcium accumulation. The animal data have been compelling that cyclosporin A (CsA) has therapeutic benefits in TBI models. However, the variability of study designs from the clinical stud- ies has made the outcome data difficult to interpret. The safety of CsA use in TBI has been demonstrated, but additional investi- gation is needed to clarify the efficacy of the drug (Lulic, Burn, Bae, van Loveren, & Borlongan, 2011).
Numerous other vitamins, minerals, and antioxidant agents are being investigated as potential therapeutic modalities. These include nicotinamide, a soluble B-group vitamin. Animal TBI models have demonstrated beneficial effects, including reduced cortical damage, inflammation, and behavioral disruption in animals receiving infusions (Goffus, Anderson, & Hoane, 2010).
Omega-3 essential fatty acids (EFAs) have been shown in experimental TBI models to improve the blood flow, reduce the toxic effects of glutamate, and stabilize membranes. Ani- mal models have shown that specific fatty acids can be sup- plemented in the diet and provide a protective function for the brain, especially in regard to seizures (Pages et al, 2011).
An antioxidant, !-lipoic acid, has also shown neuroprotective effects in an animal model by reducing inflammatory markers, preserving BBB permeability, and reducing brain edema (Toklu et al, 2009). Another agent called Resveratrol, which is a polyphenol, also has antioxidant properties and has been shown to improve behavioral outcome in a rat TBI model (Maroon & Bost, 2011). Zinc protoporphyrin has also been shown to attenuate brain edema and BBB permeability in an animal model (Vannemreddy et al, 2006).
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1060
REFERENCES
1061
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1061
1062
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1062
1063
CHAPTER 36
Laura Rosenthal
PATHOPHYSIOLOGY, 1063 Types of Heart Failure
Classifications of Heart Failure
Symptoms of Heart Failure
PHARMACODYNAMICS, 1065
GOALS OF TREATMENT, 1067
RATIONAL DRUG SELECTION, 1067 Guidelines
Diagnosis of Heart Failure
Treatment Recommendations Based on Stage of Heart Failure
Cost
Additional Patient Variables
Drug Combinations
MONITORING, 1076
OUTCOME EVALUATION, 1077
PATIENT EDUCATION, 1078
H
PATHOPHYSIOLOGY
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1063
Types of Heart Failure
1064
Decreased cardiac output
Decreased systemic blood pressure
Increased sympathetic discharge
Decreased renal blood flow
Decreased oxygen supply to kidney
Increased renin release
Increased angiotensin IIIncreased norepinephrine
Increased remodelingIncreased afterloadIncreased preload
Increased heart rate
Increased contractility
Figure 36–1. Compensatory responses in heart failure.
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1064
Classifications of Heart Failure
Symptoms of Heart Failure
PHARMACODYNAMICS
1065
Table 36–1 Comparison of Classification Systems for Heart Failure (HF)
American College of Cardiology/ New York Heart Association American Heart Association
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1065
1066
Table 36–2 Drugs Commonly Used: Heart Failure
Drug Indication Dosage Form Initial Dose Target Dose
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1066
GOALS OF TREATMENT
RATIONAL DRUG SELECTION
Guidelines
Diagnosis of Heart Failure
1067
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1067
1068
S ta
ge A
A t h
ig h
ris k
fo r h
ea rt
fa ilu
re b
ut w
ith ou
t s tru
ct ur
al h
ea rt
d is
ea se
fo r
sy m
pt om
s of
h ea
rt fa
ilu re
S ta
ge B
S tru
ct ur
al h
ea rt
d is
ea se
bu t w
ith ou
t s ym
pt om
s of
h ea
rt fa
ilu re
S ta
ge C
S tru
ct ur
al h
ea rt
d is
ea se
w ith
p rio
r o r c
ur re
nt sy
m pt
om s
of h
ea rt
fa ilu
re
S ta
ge D
R ef
ra ct
or y
he ar
t f ai
lu re
re qu
iri ng
s pe
ci al
iz ed
in te
rv en
tio ns
Pa tie
nt s
w ith
• hy
pe rt
en si
on •
co ro
na ry
a rt
er y
di se
as e
• di
ab et
es m
el lit
us
or Pa
tie nt
s •
us in
g ca
rd io
to xi
ns •
w ith
fa m
ily h
is to
ry o
f ca
rd io
m yo
pa th
y
Th er
ap y
• Tr
ea t h
yp er
te ns
io n
• E
nc ou
ra ge
s m
ok in
g ce
ss at
io n
• Tr
ea t l
ip id
d is
or de
rs •
E nc
ou ra
ge re
gu la
r ex
er ci
se •
D is
co ur
ag e
al co
ho l
in ta
ke , i
lli ci
t d ru
g us
e •
AC E
in ih
ib iti
on in
ap
pr op
ria te
p at
ie nt
s (s
ee te
xt )
Pa tie
nt s
w ith
• pr
ev io
us M
I •
LV s
ys to
lic d
ys fu
nc tio
n •
as ym
pt om
at ic
v al
vu la
r di
se as
e
S tr
uc tu
ra l
he ar
t d is
ea se
D ev
el op
m en
t of
s ym
pt om
s of
h ea
rt fa
ilu re
R ef
ra ct
or y
sy m
pt om
s of
he
ar t f
ai lu
re at
r es
t
Th er
ap y
• A
ll m
ea su
re s
un de
r st
ag e
A •
AC E
in hi
bi to
rs in
ap
pr op
ria te
p at
ie nt
s (s
ee te
xt )
• B
et a
bl oc
ke rs
in
ap pr
op ria
te p
at ie
nt s
(s ee
te xt
)
Pa tie
nt s
w ith
• kn
ow n
st ru
ct ur
al h
ea rt
di
se as
e •
sh or
tn es
s of
b re
at h
an d
fa tig
ue , r
ed uc
ed e
xe rc
is e
to le
ra nc
e
Th er
ap y
• A
ll m
ea su
re s
un de
r st
ag e
A •
D ru
gs fo
r r ou
tin e
us e:
D iu
re tic
s AC
E in
hi bi
to rs
B et
a bl
oc ke
rs D
ig ita
lis •
D ie
ta ry
s al
t r es
tri ct
io n
Pa tie
nt s
w ho
h av
e m
ar ke
d sy
m pt
om s
at re
st d
es pi
te
m ax
im al
m ed
ic al
th er
ap y
(e .g
., th
os e
w ho
a re
re
cu rr
en tly
h os
pi ta
liz ed
o r
ca nn
ot b
e sa
fe ly
d is
ch ar
ge d
fro m
th e
ho sp
ita l w
ith ou
t sp
ec ia
liz ed
in te
rv en
tio ns
)
Th er
ap y
• A
ll m
ea su
re s
un de
r st
ag es
A , B
, a nd
C •
M ec
ha ni
ca l a
ss is
t de
vi ce
s •
H ea
rt tr
an sp
la nt
at io
n •
C on
tin uo
us (n
ot
in te
rm itt
en t)
IV
in ot
ro pi
c in
fu si
on s
fo r
pa lli
at io
n •
H os
pi ce
c ar
e
Fi g
u re
3 6–
2. S
ta ge
s in
t he
e vo
lu tio
n of
H F
an d
re co
m m
en de
d th
er ap
y by
s ta
ge .
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1068
Treatment Recommendations Based on Stage of Heart Failure Stage A
Angiotensin-Converting Enzyme Inhibitors
1069
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1069
Beta Blockers
Stage B
1070
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1070
Stage C
Diuretics
1071
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1071
Cardiac Glycosides
1072
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1072
Angiotensin II Receptor Blockers
Calcium Channel Blockers
Nitrates
Stage D
1073
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1073
Patients With Heart Failure With Preserved Ejection Fraction (HF-pEF)
Cost
Additional Patient Variables Concomitant Diseases
Chronic Atrial Fibrillation and the Use of Anticoagulants
Diabetes and the Use of ACE Inhibitors
1074
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1074
Hypertension and the Early Use of Diuretics
Hyperlipidemia and the Use of Statins
Other Comorbidities
1075
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1075
Age and Gender
Pregnancy
Drug Combinations
MONITORING
1076
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1076
OUTCOME EVALUATION
PATIENT EDUCATION
1077
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1077
REFERENCES
1078
HEART FAILURE P ATIENT
EDUCATI ON
Related to the Overall Treatment Plan and Disease Process
■■ Pathophysiology of heart failure, its prognosis, and its long-term effects on other organs of the body besides the heart
■■ Role of lifestyle modifications, including dietary and activity modifications, in improving prognosis and keeping the number and cost of required drugs down
■■ Importance of adherence to the treatment regimen
■■ Self-monitoring of symptoms of worsening failure, including daily weights
■■ What to do when symptoms worsen
■■ Need for regular follow-up visits with the primary care provider
Specific to the Drug Therapy
■■ Reason for the drug being given and its anticipated action in the disease process
■■ Doses and schedules for taking the drug
■■ Possible adverse effects and what to do if they occur
■■ Coping mechanisms for complex and costly drug regimens
■■ Interactions between other treatment modalities and these drugs
Reasons for Taking the Drug(s)
Patient education about specific drugs is provided in Chapter 16. Specifically for HF, additional information includes the following: These drugs are given to reduce mortality, reduce symptoms, and improve functional status. Some drugs do all of these (ACE inhibitors); most do only one. The expectations should be clear about what the drugs can and cannot do. HF is a chronic condition that rarely occurs in a short period of time, and it is not likely to be corrected in a short period of time, if at all. Patients with HF must understand the seriousness of this diagnosis, including the 5-year mortality rate of 50% and the potential need for surgeries such as heart transplantation. All of this must be done while maintaining hope and emphasizing that a good quality of life is possible.
Drugs as Part of the Total Treatment Regimen
The total treatment regimen includes sodium restriction and avoidance of excessive fluid intake. Diuretics reduce fluid volume and may interact with dietary restrictions, resulting in orthostatic hypotension. Care should be taken not to reduce fluid volume too quickly, which exacerbates the problem of decreased cardiac output and may lead to hypotension or renal insufficiency. Patients should report symptoms of fluid volume deficit. They should be told to rise slowly from a supine to a standing position to permit the body to redistribute body fluids. Sodium restriction may lead some patients to seek salt substitutes that have a potassium salt as part of their contents. For patients taking ACE inhibitors, this can result in exces- sively high potassium levels. Such salt substitutes should be avoided. Nonsalt herbal seasoning is more appropriate.
Regular aerobic exercise such as walking or cycling may improve functional status and decrease symptoms. Regular, gradually increased exercise may lead to enough improvement, in some cases, to reduce the drugs needed. Timing of exer- cise with the peak action of drugs is important. Patients are often able to predict the timing of voiding after taking a diuretic or times when other drugs are more likely to produce dizziness. Exercise timing should take these into consideration.
Adherence Issues
Nonadherence with the treatment regimen in HF may reduce life expectancy and certainly affects functional status. Health-care providers should be aware of the potential problem of nonadherence, discuss the importance of adherence at each follow- up visit, and assist patients in removing barriers to adherence (e.g., cost, adverse effects, or complexity of the regimen).
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1078
1079
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1079
1080
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1080
1081
CHAPTER 37
James Raper • Gina Dobbs
PATHOPHYSIOLOGY, 1082 HIV-1
HIV-2
Transmission
Stages—Natural History of HIV
HIV Life Cycle
GOALS OF TREATMENT, 1085 Rationale for ART Medication Selection
Principles of Therapy
INITIATING ART MEDICATIONS, 1086 Medications Used to Treat HIV
Reverse Transcriptase Inhibitors
Protease Inhibitors
Integrase Strand Transfer Inhibitors
CCR5 Antagonists
Fusion Inhibitors
COST CONSIDERATIONS, 1094 AIDS Drug Assistance Program
Patient Assistance Programs
MEDICATION RESISTANCE, 1096 Pretreatment
Virological Failure
Causes of ART Failure
DISCONTINUATION OR INTERRUPTION OF ANTIRETROVIRAL MEDICATIONS, 1099 Monitoring
OUTCOME EVALUATION, 1099
CONCLUSION, 1100
N
3827_Ch37_1081-1102 02/07/15 2:45 PM Page 1081
PATHOPHYSIOLOGY
HIV-1
1082
3827_Ch37_1081-1102 02/07/15 2:45 PM Page 1082
HIV-2
Transmission
Stages—Natural History of HIV
Viral Structure and Genetic Material
HIV Life Cycle
1083
3827_Ch37_1081-1102 02/07/15 2:45 PM Page 1083
Fusion and Entry
Reverse Transcription and Integration
Transcription and Translation
Assembly, Budding, and Maturation
1084
1. Fusion of HIV to the host cell surface.
2. HIV RNA, reverse transcriptase, integrase, and other viral proteins enter the host cell.
3. Viral DNA is formed by reverse transcription.
4. Viral DNA is transported across the nucleus
and intergrates into the host DNA.
5. New viral RNA is used as genomic RNA and to make viral proteins.
6. New viral RNA and proteins move to the cell surface and a new, immature HIV forms.
7. The virus matures by protease-releasing indivdual HIV proteins.
Viral DNA
Host DNA
New viral RNA
Viral RNA
gp120
CD4
Co-receptor (CCR5 or CXCR4)
Host cell
Mature Virion
Reverse transcriptase
Intergrase
Preintegration complex
Figure 37–1. HIV replication cycle. Courtesy: National Institute of Allergy and Infectious Diseases (NIAID, 2013).
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1084
GOALS OF TREATMENT
Rationale for ART Medication Selection
Principles of Therapy
1085
BOX 37–1 HIV TREATMENT GOALS
• Improve quality of life • Obtain maximal and durable suppression of HIV • Prevent vertical HIV transmission • Prolong survival • Reduce HIV-related morbidity • Reduce transmissibility of HIV • Restore and preserve immunological function
BOX 37–2 PREDICTORS OF ART VIROLOGICAL SUCCESS
• High-level patient adherence to ART regimen • High potency of antiretroviral medication regimen • Higher baseline CD4 T-cell count • Low baseline HIV plasma viral RNA level • Rapid (i.e., equal to or greater than 1 log10 in 1 to
4 mo) reduction of viral RNA level in response to ART
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1085
INITIATING ART MEDICATIONS
1086
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1086
1087
BOX 37–3 POTENTIAL BENEFITS AND RISKS OF ART
Potential Benefits of Early Therapy
• Maintenance of a higher CD4 T-cell count and prevention of potentially irreversible damage to the immune system • Decreased risk for HIV-associated complications that can sometimes occur at CD4 counts more than 350 cells/!L,
including tuberculosis, non-Hodgkin lymphoma, Kaposi’s sarcoma, peripheral neuropathy, HPV-associated malignan- cies, and HIV-associated cognitive impairment
• Decreased risk of nonopportunistic medical conditions, including cardiovascular disease, renal disease, liver disease, and non–AIDS associated malignancies and infections
• Decreased risk of HIV transmission to others, which will have positive public health implications
Potential Risks of Early Therapy
• Treatment-related side effects and toxicities • Viral resistance to medications because of incomplete viral suppression, resulting in loss of future treatment options • Less time for the patient to learn about HIV and its treatment and less time to prepare for the need for adherence
to ART • Increased total time exposed to medication, with greater chance of treatment fatigue • Premature use of ART before the development of more effective, less toxic, and/or better studied combinations of
antiretroviral medications • Transmission of medication-resistant virus in patients who do not maintain full viral suppression
Table 37–1 ART Medications and Treatment Strategies, Naïve Patients
NNRTI-Based Regimen
PI-Based Regimens (in alphabetical order)
INSTI-Based Regimen
Preferred Regimen† for Pregnant Women
NNRTI-Based Regimens (in alphabetical order)
PI-Based Regimens (in alphabetical order)
INSTI-Based Regimen
NNRTI-Based Regimen
Comments
Comments
Comments
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1087
1088
Table 37–1 ART Medications and Treatment Strategies, Naïve Patients—cont’d
PI-Based Regimen
INSTI-Based Regimen
CCR5 Antagonist-Based Regimens
Medications Used to Treat HIV
Reverse Transcriptase Inhibitors
Nucleoside Reverse Transcriptase Inhibitors
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1088
1089
Ta b
le 3
7– 2
A n
ti re
tr o
vi ra
l A g
en t
C h
ar ac
te ri
st ic
s
R en
al F
ai lu
re D
o si
n g
Li ve
r Fo
o d
C
rC l
C rC
l C
rC l
Fa il
u re
D
ru g
N am
e Fo
rm U
su al
A d
u lt
D o
se Ef
fe ct
s 3
0 –5
9 m
L/ m
in 1
0 –2
9 m
L/ m
in <
1 0
o r
D ia
ly si
s D
o si
n g
T o
xi ci
ty
N u
cl eo
si d
e R
ev er
se T
ra n
sc ri
p ta
se In
h ib
it o
rs (N
R TI
s)
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1089
1090 Ta
b le
3 7–
2 A
n ti
re tr
o vi
ra l A
g en
t C
h ar
ac te
ri st
ic s—
co n
t’ d
R en
al F
ai lu
re D
o si
n g
Li ve
r Fo
o d
C
rC l
C rC
l C
rC l
Fa il
u re
D
ru g
N am
e Fo
rm U
su al
A d
u lt
D o
se Ef
fe ct
s 3
0 –5
9 m
L/ m
in 1
0 –2
9 m
L/ m
in <
1 0
o r
D ia
ly si
s D
o si
n g
T o
xi ci
ty
Pr o
te as
e In
h ib
it o
rs (P
Is )
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1090
1091
N o
n n
u cl
eo si
d e
R ev
er se
T ra
n sc
ri p
ta se
In h
ib it
o rs
(N N
R TI
s)
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1091
1092 Ta
b le
3 7–
2 A
n ti
re tr
o vi
ra l A
g en
t C
h ar
ac te
ri st
ic s—
co n
t’ d
R en
al F
ai lu
re D
o si
n g
Li ve
r Fo
o d
C
rC l
C rC
l C
rC l
Fa il
u re
D
ru g
N am
e Fo
rm U
su al
A d
u lt
D o
se Ef
fe ct
s 3
0 –5
9 m
L/ m
in 1
0 –2
9 m
L/ m
in <
1 0
o r
D ia
ly si
s D
o si
n g
T o
xi ci
ty
Fu si
o n
In h
ib it
o rs
C C
R 5
A n
ta g
o n
is ts
In te
g ra
se S
tr an
d T
ra n
sf er
In h
ib it
o rs
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1092
Nonnucleoside Reverse Transcriptase Inhibitors
Protease Inhibitors
Integrase Strand Transfer Inhibitors
1093
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1093
CCR5 Antagonists
Fusion Inhibitors
COST CONSIDERATIONS
AIDS Drug Assistance Program
Patient Assistance Programs
1094
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1094
1095
Table 37–3 Brand-Name Antiretroviral Medications, Usual Adult Dosing, and Monthly Average Wholesale (AWP) Price by Mechanistic Class
RTV AWP Generic Name Brand Name Usual Adult Dose AWP Price* Total
Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (N/NTRTIs)
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Protease Inhibitors (PIs)
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1095
1096
Table 37–3 Brand-Name Antiretroviral Medications, Usual Adult Dosing, and Monthly Average Wholesale (AWP) Price by Mechanistic Class—cont’d
RTV AWP Generic Name Brand Name Usual Adult Dose AWP Price* Total
Fusion Inhibitors (FIs)
CCR5 Antagonists
Integrase Strand Transfer Inhibitors (INSTIs)
Fixed-Dose Tablets From More Than One Class
MEDICATION RESISTANCE
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1096
1097
Table 37–4 Resistance Mutations to Antiretroviral Medicine
Antiretroviral Medicine Codon Mutation
Multi-NRTI Resistance: 69 Insertion Complex (affects all NRTIs)
Multi-NRTI Resistance: 151 Insertion Complex (affects all NRTIs)
Multi-NRTI Resistance: Thymidine Analogue-Associated Mutations (TAMS; affects all NRTIs)
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Mutation in the Protease Gene Associated With Resistance to Protease Inhibitors (PIs)
PIs Critical Secondary
Mutations in the Envelope Gene Associated With Resistance to Fusion Inhibitors (FIs) and CCR5 Antagonists
Mutations in the Integrase Gene Associated With Resistance to Integrase Inhibitors (IIs)
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1097
Pretreatment
Virological Failure
Causes of ART Failure
1098
BOX 37–4 HIV DRUG RESISTANCE TESTING: EIGHT IMPORTANT CONSIDERATIONS AND LIMITATIONS
1. Biological cutoffs are based on normal distribution of susceptibility to drug for wild-type strain from treatment-naïve patients.
2. Clinical cutoffs are based on data from clinical trials or cohort studies to determine change in susceptibility that results in reduced virological response.
3. Clinical phenotypic cutoff values include diminished versus no response; partial activity may be useful when treatment options are limited. Analysis compli- cated by prior drug exposure and activity of other drugs in salvage regimen.
4. Consider phenotyping over genotyping when treat- ment history is complex and/or significant resistance is expected.
5. May detect resistance only in species that make up more than 10% to 20% of viral population.
6. Measures susceptibility to individual medicines, not medication combinations.
7. Phenotypic resistance reported as fold change in IC50 for the test strain versus reference wild-type strain.
8. Testing should be performed on therapy whenever possible or within 4 weeks of stopping antiretroviral medicines and is not recommended when VL is less than 1,000 copies/mL.
BOX 37–5 FACTORS ASSOCIATED WITH ART FAILURE
Patient factors at baseline:
• AIDS diagnosis • Comorbid conditions (e.g., affective mental health
disorders and active substance use) • Earlier calendar year of starting ART when less-
potent regimens or more poorly tolerated antiretroviral medicines were used
• Higher pretreatment HIV RNA level (regimen- specific)
• Lower pretreatment or nadir CD4 T-cell count • Pretreatment drug-resistant virus • Prior ART failure, with development of drug resis -
tance or cross-resistance • ART adverse effects and toxicity • Nonadherence to ART and medical appointments • Suboptimal pharmacokinetics caused by variable
absorption, metabolism, and/or penetration into HIV reservoirs, food or fasting requirements, ad- verse drug–drug interactions with concomitant medications and foods
• Suboptimal potency of the ART regimen • Unknown causes
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1098
DISCONTINUATION OR INTERRUPTION OF ANTIRETROVIRAL MEDICATIONS
Monitoring
OUTCOME EVALUATION
1099
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1099
CONCLUSION
1100
On The Horizon FIVE DRUGS FOR THE FUTURE
New HIV-drug development continues.
• GS-7340 (tenofovir alafenamide, TAF), a new oral pro- drug, was well tolerated and had better antiviral activity at lower doses than tenofovir disoproxil fumarate (Viread, TDF) in early studies. Reportedly, in 38 people over 10 days, 25 mg of GS-7340 outperformed 300 mg of the currently approved tenofovir formulation. Along with fewer side effects, GS-7340 showed higher potency, which could mean longer and better viral suppression over time.
• Dolutegravir (GSK-572) is an investigational integrase inhibitor, but it has distinguished itself from the two ap- proved integrase inhibitors, raltegravir (Isentress) and elvitegravir. Dolutegravir has a long half-life of 15 hours, indicating it can be taken once a day. It does not require pharmacokinetic boosting. Although resistance can occur, dolutegravir shows activity against raltegravir- and elvitegraivr-resistant viral strains. The drug may be coformulated in a once-daily pill with abacavir and lamivudine.
• S/GSK-1265744 (744), an integrase inhibitor similar to dolutegravir, shows high potency and an exceedingly long half-life. Orally at once-daily doses of 30 mg, pa- tients showed a median 2.6 log reduction in viral load. Interestingly, when using nanotechnology to formulate 744 to be injected subcutaneously or intramuscularly, a single dose showed a half-life between 21 and 50 days. After a single dose, patients had detectable levels of 744 up to 48 weeks after injection. Like dolutegravir, 744 seems to have a high barrier to drug resistance. 744 showed activity against raltegravir- and elvitegraivr- resistant viral strains. In terms of safety, there were some injection-site reactions and nodules associated with sub- cutaneous dosing. But conceivably, 744 could be taken as infrequently as every 3 months for treatment, or even as PrEP (pre-exposure prophylaxis).
• Cenicriviroc (CVC), an investigational CCR5 antagonist, not only antagonize CCR5 binding, it also antagonizes CCR2 binding. CCR2 is a receptor that sits on the surface of macrophages and may be involved in inflammation. CVC showed potent antiretroviral activity. Cenicriviroc has been found to be well absorbed and within the ex- pected therapeutic range of potency. Further studies will assess the safety, efficacy, and effect of CCR2 inhibition on inflammatory biomarkers.
• Albuvirtide is a fusion inhibitor like enfuvirtide that of- fers a lot of activity against HIV but requires twice-daily injections. Albuvirtide, on the other hand, is an investi- gational fusion inhibitor that when given intravenously has a long average half-life of 11 days, warranting weekly dosing. Albuvirtide has a similar design to enfu- virtide. It is a peptide that is an analogue of gp41, one of the envelope proteins on HIV’s surface, and thereby blocks HIV through CD4 membrane fusion. In very early studies, Albuvirtide was generally well tolerated, with no injection-site reactions and no serious adverse events.
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REFERENCES
1101
HIV DISEASE PA TIENT
EDUCATI ON
Related to the Overall Treatment Plan/Disease Process
■■ After diagnosis, patients need to be educated regard- ing what it means to be HIV positive (they are in- fected with the HIV virus) versus what AIDS is (their immune system has been affected and they are at risk for life-threatening infections).
■■ Patients need education regarding the chronicity of HIV treatment. The clinician may make an analogy of HIV disease to diabetes; diabetics need insulin for the rest of their life and patients with HIV disease must take their medications daily for the rest of their lives.
■■ HIV-infected patients need to be vaccinated with the recommended adult vaccines, including an annual influenza vaccine.
■■ Symptoms of opportunistic infections should be dis- cussed so that patients receive early treatment.
Specific to the Drug Therapy
■■ Highly active antiretroviral therapy (HAART) is a combination of medications and all should be taken together as prescribed to decrease viral load.
■■ Adherence to HAART is critical to prevent the development of drug resistance.
Reasons for Taking the Drug(s)
■■ Prevention of serious complications from AIDS.
■■ Prevention of transmission of infection to the uninfected (public health issue).
Drugs as Part of the Total Treatment Regimen
■■ Importance of seeking treatment when symptoms appear.
■■ Patients need routine preventive care, including lipid monitoring, cardiovascular health screening, cervical cancer screening, STI screening, and immunizations.
Adherence Issues
■■ Importance of following the HAART treatment regi- men instructions to prevent resistance and to keep viral loads low.
■■ Importance of contacting the health-care provider if side effects or rash appears.
■■ The potential for drug interactions.
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1102
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1102
1103
CHAPTER 38
Marylou V. Robinson
HORMONE REPLACEMENT THERAPY, 1103 Pathophysiology
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
OSTEOPOROSIS, 1114 Pathophysiology
Ethnic Differences
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Combination Therapy
Monitoring
Outcome Evaluation
HORMONE REPLACEMENT THERAPY
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1103
Pathophysiology
!
Physiological Effects of Estrogen
Physiological Effects of Progestin
1104
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1104
Physiological Effects of Androgens
Menopausal Changes in Hormones
1105
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1105
Pharmacodynamics Estrogens
Progestogens
1106
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1106
Goals of Treatment
Rational Drug Selection
Cardiac Disease Prevention
Osteoporosis Prevention
1107
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1107
Cognitive Performance, Sleep Disturbance, and Skin Changes
Relief of Perimenopausal and Postmenopausal Symptoms
1108
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1108
1109
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1109
1110
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1110
Progestin Therapy
Combination Therapy with Estrogen and Progestins
1111
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1111
Testosterone Therapy
Monitoring
Outcome Evaluation
Patient Education
OSTEOPOROSIS
1112
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1112
1113
H or
m on
e re
pl ac
em en
t t he
ra py
(H R
T) /
E st
ro ge
n re
pl ac
em en
t t he
ra py
(E R
T)
N eg
at iv
e fa
m ily
hi st
or y
fo r C
H D
?
Pa tie
nt p
re fe
re nc
e
Po si
tiv e
fa m
ily h
is to
ry fo
r br
ea st
c an
ce r w
ith se
co nd
-d eg
re e
cl os
e re
la tiv
e
N o
sy m
pt om
s; pa
tie nt
p re
fe re
nc e
Po si
tiv e
fo r f
am ily
ca rd
io va
sc ul
ar d
is ea
se (C
V D
) Po
si tiv
e fo
r sy
m pt
om s
U se
E R
T if
no C
H D
is p
re se
nt .
C on
si de
r t ra
ns de
rm al
.
If ut
er us
is p
re se
nt co
ns id
er m
ic ro
ni ze
d pr
og es
tin .
U se
H R
T/ E
R T.
A dd
p ro
ge st
er on
e if
ut er
us is
p re
se nt
.
N o
fo r H
R T/
E R
T
O ffe
r r al
ox ife
ne ,
al en
dr on
at e,
c al
ci to
ni n.
N o
or y
es fo
r H
R T/
E R
T
R ee
va lu
at e
be ne
fit ve
rs us
ri sk
a nn
ua lly
.
Ye s
fo r H
R T/
E R
T N
o fo
r H R
T/ E
R T
R ee
va lu
at e
ris k
ve rs
us be
ne fit
s an
nu al
ly. U
se c
al ci
um , v
ita m
in D
w ith
a ll
th er
ap ie
s.
Fi g
u re
3 8–
1. T
re at
m en
t al
go rit
hm : H
or m
on e
re pl
ac em
en t
th er
ap y/
es tr
og en
r ep
la ce
m en
t th
er ap
y.
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1113
Pathophysiology Normal Bone Physiology
1114
HORMONE REPLACEMENT THERAPY P ATIENT
EDUCATI ON
Related to the Overall Treatment Plan/Disease Process
■■ Pathophysiology of the changes that take place in the female physiology at menopause that make a woman vulnerable to atrophy of the genital organs, vasomotor instability, and emotional lability, and when lower estrogen levels cause undesirable lipid patterns
■■ Role of lifestyle modifications and the various treatment protocols and medications available
■■ Importance of adherence to the treatment regimen
■■ Need for regular follow-up visits with the primary care provider, including annual screening tests such as mammography
Specific to the Drug Therapy
■■ Reasons for the drug’s being given
■■ Doses and schedules for taking the drug
■■ Possible adverse effects and what to do if they occur, especially if uterine bleeding occurs
■■ Interactions between other treatment modalities and these drugs
Reasons for Taking the Drug(s)
Additional information includes the following: Quality-of-life issues such as relief of hot flashes; target organ atrophy preven- tion; treatment of osteoporosis; prevention of early heart disease, which may be more successful, especially in families who have a hereditary tendency for cardiac disease; and the preliminary data on retention of cognition, which seems promising.
Drugs as Part of the Total Treatment Regimen
The total treatment regimen includes the following: therapy with alternative herbs and healthier lifestyle, which may relieve symptoms but have not proved to bestow reduced morbidity, as has drug therapy; hormonal therapy is indicated for vaginal atrophy and bladder outlet syndrome; and referral to an appropriate specialist to provide the appropriate care when adverse effects occur as a result of estrogen therapy.
Adherence Issues
Nonadherence to the treatment regimen may be a result of various causes. Concerns about the WHI results should be dis- cussed with correction of any inaccurate interpretations of media messages. Nonadherence due to the possible risk of can- cer should be discussed, and the absolute risk of cancer rather than relative risk of cancer should be calculated annually. The possibility of minor discomforts, such as breast tenderness, bloating, fluid retention, and the need for follow-up visits, should be discussed prior to therapy. If irregular or unexpected bleeding occurs, patients should be advised to contact their health-care provider for modifications to the treatment regimen rather than stop therapy on their own.
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1115
Table 38–1 Medical Conditions and Drugs That Increase the Risk for Development of Osteoporosis
Medical Conditions
Drugs
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1115
Bone Loss (Osteoporosis)
Ethnic Differences
African American Women
1116
Normal Osteoporotic Figure 38–2. Micrographs of normal and osteoporotic bone.
Table 38–2 Risk Factors for Osteoporosis and Resultant Fractures
Risk Factors for Osteoporosis
Risk Factors for Fracture Secondary to Osteoporosis
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1116
Asian Women
Hispanic Women
Pharmacodynamics
1117
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1117
Goals of Treatment
Rational Drug Selection Estrogen Therapy
1118
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1118
Calcium Therapy
1119
Table 38–3 Recommendations for Adequate Dietary Calcium Intake in the United States
Calcium Intake Upper Intake Age (mg/d) Levels (mg)
Table 38–4 Calcium Preparations
Drug Active Calcium How Supplied
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1119
Bisphosphonate Therapy
1120
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1120
Selective Estrogen Receptor Modulators
Human Parathyroid Hormone
1121
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1121
Combination Therapy
Comparisons Monitoring
1122
Table 38–5 Fracture Risk Reduction Comparisons
Vertebral Fracture Non-Vertebral Reduction Reduction
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1122
1123
Prevention of osteoporosis (no current osteoporosis)
Diet Exercise Other
DXA: BMD between –1 and –2.5 SD of young
normal (osteopenia)
Alendronate 5 mg/day or 35 mg/wk OR
Risendronate 5 mg/day or 35 mg/wk OR
Raloxifen 60 mg/day
DXA: > –2.5 SD of young normal (osteoporosis)
If fracture risk
See Figure 38–4
Calcium intake: Adults 19–50 yr: 1,000 mg/day Adults >50 yr: 1,200 mg/day Postmenopausal: 1,200 mg/day Vitamin D: Adults 19–50 yr: 600 IU/day Adults 51–70 yr: 800 IU/day Adults >70 yr: 800 IU/day Poor sun exposure: 800 IU/day
Low-impact weight-bearing or aerobic exercise for at least 20 min 3 times/wk
Smoking cessation: (see Chapter 43) Alcohol: Limit alcohol to no more than 2 drinks per day. One drink = 12 oz of beer, 5 oz of wine or 1.5 oz of 80-proof distilled spirits
Lifestyle modifications
Figure 38–3. Prevention of osteoporosis in patients without the disease.
Estrogen
Calcium
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1123
1124
Low-impact fracture Male with idiopathic or hypogonadal osteoporosis
Long-term glucocorticoid
therapy
1. No contraindication to estrogen therapy
2. Cost considerations
1. Contraindication to estrogen therapy
2. Risk for breast cancer 3. Hyperlipidemia
Raloxifen 60 mg/day
Teriparatide
Estrogen (see HRT) Alendronate 10 mg/day or 70 mg/wk
Ibandronate 2.5 mg/day (equivalent monthly dose) Risedronate 5 mg/day or
35 mg/wk
1. Contraindication to estrogen therapy or male
2. Frail elderly (>80 yr with or without fracture)
(See Fig. 38–3 with fracture risk and
osteopenia)
If history of fracture or failed other therapy
Lifestyle modifications (see Fig. 38–3)
If postmenopausal with multiple fractures, intensify bisphosphonate therapy or increase bisphosphonate intensity or terparatide or consider IV bisphosphonate or teriparatide
Figure 38–6. Treatment algorithm: Osteoporosis. (Adapted from Osteo- porosis and African American Women; Osteoporosis and Asian American Women; Osteoporosis and Hispanic Women [all from NIAMS documents, 2005]; and National Osteoporosis Foundation, 2004, Physician’s Guide.)
Table 38–6 Common Methods for Bone Density Measurements
Test Sites Measured Comments
Bisphosphonates SERMs
Outcome Evaluation
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1125
OSTEOPOROSIS P ATIENT
EDUCATI ON
Patient education should include a discussion of information related to the overall treatment plan as well as that specific to the drug therapy, reasons for taking the drug, drugs as part of the total treatment regimen, and adherence issues. Patients who have taken teriparatide should take advantage of the voluntary patient registry to help track the rare occurrence of osteosarcoma.
Related to the Overall Treatment Plan/Disease Process
■■ Pathophysiology of the dynamic relationship between the osteoclasts and osteoblasts in the process of bone metabo- lism to help the patient understand how the lack of estrogen begins a cascade of events ending with the increased risk of osteoporosis in the early years after cessation of menses. For men, discussion of the role of other factors is important.
■■ The role of excessive intake of alcohol, nicotine, and caffeine and low intake of calcium and vitamin D as modifiable risks for osteoporosis and how nondrug treatments such as diets high in calcium and vitamin D, exercise, and avoidance of the high-risk lifestyles can help to prevent osteoporosis.
■■ An understanding of how knowledge of family history, ethnicity, and genetic characteristics helps to identify patients with nonmodifiable risk factors for osteoporosis.
■■ Importance of adherence to the treatment regimen
■■ Importance of supplementing the diet with additional calcium (up to 1,500 mg) and vitamin D (800 mg) to the osteoporosis therapy
■■ Self-monitoring of symptoms
■■ What to do when symptoms worsen
■■ Need for regular follow-up visits with the primary care provider and for screening tests such as BMDs every 2 years.
Specific to the Drug Therapy
■■ Reason for the drug(s) to be taken and anticipated action in the disease process
■■ Doses and schedules for taking the drug(s)
■■ Possible adverse effects and what to do if they occur
■■ Interactions between other treatment modalities and these drugs
Reasons for Taking the Drug(s)
Patient education specifically for osteoporosis should include the following: that prevention of osteoporosis is more successful than having to treat it later, especially in those who have a hereditary tendency for bone loss disease; treatment of fractures is far more expensive than drug therapy; and postmenopausal fractures are associated with early loss of independent living and reduced life expectancy.
Drugs as Part of the Total Treatment Regimen
The total treatment regimen includes lifestyle modification: healthy diet, dietary supplements, and exercise. However, these lifestyle modifications may not be enough, especially in older patients. Some form of drug therapy is usually neces- sary. A variety of therapies are available, and selection of estrogen versus nonestrogen therapy is possible with the same results for prevention and treatment of spine, hip, and wrist fractures associated with osteoporosis.
Adherence Issues
Adherence issues include the following: ■■ Media reports about disease and drug therapies have an increasing impact on patients and primary care practices.
■■ Membership in health maintenance organizations may affect the choice of drugs patients will receive.
■■ Patients’ fears or issues about drug therapy may not be based on facts.
■■ Drug therapy educational handouts should be available to patients and their families.
■■ Monitoring appointments are problematic if patients are homebound or transportation is difficult.
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REFERENCES
1126
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1126
1127
3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1127
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1129
CHAPTER 39
Marylou V. Robinson
C
PATHOPHYSIOLOGY
PATHOPHYSIOLOGY, 1129 Exogenous Pathway
Endogenous Pathway
Atherogenesis
VDRL Levels
GOALS OF TREATMENT, 1132
RATIONAL DRUG SELECTION, 1133 Risk Stratification
Treatment Algorithms
Additional Patient Variables
Cost
MONITORING, 1149
OUTCOME EVALUATION, 1150
PATIENT EDUCATION, 1150
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1129
Exogenous Pathway
Endogenous Pathway
Atherogenesis
1130
On The Horizon
Drugs in the pipeline are seeking to interfere with the synthe- sis of PCSK9 (proprotein convertase subtilisin/kexin type 9) in the liver. This liver protein is part of the natural synthesis of cholesterol in the body. If blocked with a targeted RNA particle, cholesterol levels drop (Fitzgerald et al, 2013).
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1130
1131
VLDL, LDL, HDL synthesized by liver
VLDL in plasma VLDL in arterial wallHDL in plasma
Excess LDL embedded in arterial wall undergoes oxidation and takes up free fatty acids from VLDL to
produce cholesterol within the arterial lumen.
Macrophages within the vessel wall take up the
cholesterol to become foam cells (the basic unit of atherosclerotic plaque).
HDL takes up excess cholesterol from arterial wall
and carries it to the liver.
Metabolized by the liver
LDL in plasma
Excreted in bile
LDL in arterial wall
Hydrolyzed to IDL and enriched with
cholesterol by hepatic triglyceride lipase
Figure 39–1. Relationship of lipid metabolism to atherosclerotic plaque formation. Excess LDL embedded in the arterial wall undergoes oxidation and takes up free fatty acids from VLDL to produce cholesterol within the arterial lumen. If the excess cholesterol is not taken up by HDL and carried to the liver, macrophages within the vessel wall create atherosclerotic plaque from this excess cholesterol.
Table 39–1 Factors That Contribute to Low HDL Cholesterol Levels
VDDL Levels
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GOALS OF TREATMENT
1132
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1132
RATIONAL DRUG SELECTION
Risk Stratification
1133
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1133
1134
Table 39–2 Major Risk Factors for Coronary Heart Disease (CHD) (Exclusive of LDL Cholesterol)
Risk Factor Positive Risk Negative Risk
Table 39–3 Factors to Be Considered in Future Guidelines
Table 39–4 Individualized Considerations When Risk Assessment Places Patient in Uncertain Category for Pursuing Statin Therapy
Support Raising No Support for Factor Risk Score Revising Risk Score
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1134
High Risk: CVD or CV Risk Equivalent
Lower Risk: Zero or One Risk Factor
1135
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1135
Treatment Algorithms Lifestyle Modifications
1136
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1136
Drug Therapy
1137
• Emphasize healthy, balanced diet. • Encourage moderate physical activity. • Consider referral to a dietitian.
• Reinforce healthy diet. • Consider adding plant stanols/sterols. • Increase fiber intake. • Consider referral to a dietitian.
• Initiate Tx for metabolic syndrome.
• Intensify weight management and physical activity.
• Increase fiber intake. • Consider referral
to a dietitian.
Visit 1: Begin lifestyle therapies
6 wk
Visit 2: Evaluate LDL response If LDL reduction not achieved,
intensify LDL-lowering Tx.
6 wk
Visit 3: Evaluate LDL response. If LDL reduction not achieved,
consider adding drug Tx.
Visit N: Monitor adherence to TLC.
Q 4–6 mo
Figure 39–2. Model of steps in Therapeutic Lifestyle Changes (TLC).
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1137
1138
Table 39–6 Definitions of High-to Low-Intensity Statin Treatment
High-Intensity Moderate-Intensity Low-Intensity Rx Daily Rx Daily Rx Daily
* Therapeutic options include intensifying LDL-lowering dietary or drug therapies, emphasizing weight reduction and increased physical activity, adding drugs to lower triglycerides, and intensifying control of other risk factors (ATP III).
CHD and CHD risk equivalents
LDL <100
LDL <100
LDL 100–129
LDL 100–129
LDL >130
TLC + control other risk factors
TLC + therapeutic options
TLC + LDL-lowering drug(s)
Continue TLC and current drug(s).
Consider other therapeutic options.*
The LDL cholesterol goal is <100 mg/dL (Intense Therapy).
Figure 39–3. Traditional therapeutic approaches for patients with CHD or CHD risk equivalents.
Table 39–5 The Four Statin Benefit Groups
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1138
Drug Therapy
1139
Table 39–7 ATP III Classification of LDL Cholesterol (reference only)
LDL Cholesterol Level (mg/dL) Category
Table 39–8 ATP III Low-Density Lipoprotein Goals (reference only)
LDL Cholesterol Patient Category Goal (mg/dL)
Figure 39–4. Traditional approaches for patients with multiple risk factors and 10 year CHD risk 10% to 20%.
Multiple (2+) risk factors 7-yr risk 10%–20%
LDL >130
LDL >130 LDL <130
LDL <130
TLC
3 mo
Control other risk factors Public health message on
healthy life habits Reevaluation in 1 yr
Continue TLC.Continue TLC and consider adding
LDL-lowering drugs.
The LDL cholesterol goal is <130 mg/dL. Drugs can be considered if necessary to attain the LD cholesterol goal if the LDL cholesterol level is >130 mg/dL after a trial of TLC (not targets, but general preferred range based on risk).
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1139
1140
LDL <130
Multiple (2+) risk factors 7-yr risk <10%
LDL >130
LDL >160 LDL <160
TLC Control other risk factors Public health message on
healthy life habits Reevaluation in 1 yr
Continue TLC.Continue TLC and consider adding
LDL-lowering drugs.
The LDL cholesterol goal is <130 mg/dL. Drug therapy can be considered if LDL cholesterol is >160 mg/dL after a trial of TLC (not targets, but desired range based on risk).
3 mo
0–1 risk factor (7-yr risk usually <10%)
LDL >160
LDL >190 LDL <160
LDL <130
TLC Public health message on healthy life habits
Reevaluation in 5 yr
Public health message on healthy life habits Consider drugs if
benefits outweigh risk.
Continue TLC.Continue TLC and consider adding
LDL-lowering drugs.
LDL 160–189
Continue TLC and LDL-lowering drugs
optional.*
The LDL cholesterol goal is <160 mg/dL. Drug therapy can be considered if LDL cholesterol is >190 mg/dL after a trial of TLC. If LDL cholesterol is 160–189 mg/dL, drug therapy is optional depending on clinical judgment and individual risks.
*Factors favoring drug use are a severe single risk factor, a family history of premature CHD, and underlying or emerging risk factors in addition to a single major risk factor.
3 mo
LDL 130–159
Figure 39–5. Traditional approaches for patients with multiple risk factors and 10 year CHD risk less than 10%.
Figure 39–6. Traditional approaches for patients with 0 or 1 risk factor.
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1140
1141
Table 39–9 Classification of Triglyceride Levels
Triglyceride Level (mg/dL) Category
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1141
Additional Patient Variables Children and Adolescents
1142
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1142
1143
Assessment
Repeat lipoprotein analysis; average with first measurement.
Obtain total blood cholesterol
Obtain lipoprotein analysis.
Blood cholesterol <170 mg/dL (acceptable)
Blood cholesterol 170–199 mg/dL (borderline)
Blood cholesterol >200 mg/dL or higher (high)
LDL cholesterol <110 mg/dL (acceptable)
LDL cholesterol >130 mg/dL (high)
LDL cholesterol 110–129 mg/dL (borderline)
LDL cholesterol <100 mg/dL (acceptable)
LDL cholesterol >130 mg/dL (high)
LDL cholesterol 100–129 mg/dL (borderline)
Repeat lipoprotein analysis within 5 yr.
Provide patient education.
Initiate clinical evaluation. Initiate Step 1, then
Step 2 diet. Set goal for LDL cholesterol.
Assess other family members.
Repeat lipoprotein analysis within 1 yr.
Provide patient education. Encourage Step 1 diet and
other risk-management strategies.
Blood cholesterol <170 mg/dL
Blood cholesterol >170 mg/dL
Family history (parent) of blood cholesterol level >240 mg/dL
Repeat cholesterol; average with
first measurement
Family history (parent or grandparent) of premature
(before age 55) cardiovascular disease
Repeat total blood cholesterol within 5 years. Provide patient education.
Figure 39–7. Management of blood cholesterol in children.
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1143
Middle-Aged Men
Women
1144
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1144
Older Adults
1145
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1145
Young Adults
African Americans
1146
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1146
Hispanic Americans
Native Americans (American Indians)
Asian and Pacific Islanders
Concomitant Disease States
1147
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1147
1148
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1148
Cost
MONITORING
1149
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1149
OUTCOME EVALUATION
PATIENT EDUCATION
1150
HYPERLIPIDEMIA P ATIENT
EDUCATI ON
Related to the Overall Treatment Plan and Disease Process
■■ Pathophysiology of lipid disorders and their long-term effects on cardiovascular morbidity and mortality
■■ Role of lifestyle modification, especially dietary therapy, in improving outcomes and keeping the number and cost of required drugs down
■■ Importance of adherence to the treatment regimen
■■ Need for regular follow-up visits with the primary care provider
Specific to the Drug Therapy
■■ Reason for the drug(s) being given and the anticipated action of the drug(s) on the disease process
■■ Doses and schedules for taking the drug(s)
■■ Possible adverse reactions, how to prevent them, and what to do if they occur
■■ Interaction between lifestyle modifications and the drug(s)
Reasons for Taking the Drug(s)
Patient education about specific drugs is provided in Chapter 16. Specific information related to hyperlipidemia includes the reasons for drug(s) being taken: Antilipidemics are given to reduce morbidity and mortality from the leading cause of death in the United States—cardiovascular disease. Discuss the risk of cardiovascular disease with the patient while maintaining the potential for good quality of life with adequate treatment.
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1150
REFERENCES
1151
HYPERLIPIDEMIAcont’d P ATIENT
EDUCATI ON
Drugs as Part of the Total Treatment Regimen
The expectations should be clear about what the drugs can and cannot do. Drugs are supplements to dietary and other lifestyle modifications, not substitutes for them. Lipid disorders are chronic conditions. Lifestyle modifications and drug regimens need to be incorporated into patients’ everyday lives. Discontinuation of treatment will result in return of lipids to pretreatment levels.
Adherence Issues
Nonadherence to the treatment regimen may increase patients’ risk for cardiovascular morbidity and reduce their life expectancy. Health-care providers should be aware of potential problems with adherence, discuss the importance of adherence at each follow-up visit, and assist patients in removing barriers to adherence, such as lack of social support and fear of side effects. Utilization of other health team members, especially the dietitian, should be maximized. Patient education booklets available from the American Heart Association and the National Cholesterol Education Program may supplement dietary instruction.
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1151
1152
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1152
1153
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1153
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1154
1155
CHAPTER 40
Marylou V. Robinson
H PATHOPHYSIOLOGY
PATHOPHYSIOLOGY, 1155 Factors That Regulate Blood Pressure
Laboratory Tests and Other Diagnostic Procedures
Classification of Blood Pressure for Adults
PHARMACODYNAMICS, 1158
GOALS OF TREATMENT, 1158 Barriers to Goal Attainment
RATIONAL DRUG SELECTION, 1159 Algorithm for Management of Hypertension
Stepped Therapy
Patient Variables
Surgery Patients
Cost
MONITORING, 1173
OUTCOME EVALUATION, 1173 Adherence Issues
PATIENT EDUCATION, 1174
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1155
Factors That Regulate Blood Pressure Baroreceptors
Endothelial Factors
Kidneys
1156
Systemic arterial pressure
Cardiac output
Stroke volume
SNS/norepinephrine activity
Heart rate
Total peripheral resistance
Arteriolar radius Blood viscosity
PNS activity SNS vasoconstrictor
Plasma norepinephrine
Local controls —O2 —K+ —CO2 —H+
Hematocrit
SNS vasodilator
End-diastolic ventricular volume
Atrial pressure
Venous return
Venous pressure Skeletal muscle pump
Blood volume
R-A-A system (kidney)
SNS activity on veins
Figure 40–1. Regulation of blood pressure. Systemic arterial pressure is determined by cardiac output and total peripheral resistance. Increases in cardiac output or total peripheral resistance increase systemic arterial pressure, and decreases in these factors decrease systemic arterial pressure. Antihypertensive drugs act at one or more of these anatomical sites of blood pressure control.
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1156
Genetic Influences
Laboratory Tests and Other Diagnostic Procedures
Classification of Blood Pressure for Adults
1157
Table 40–1 Blood Pressure Classifications and Management
Systolic BP Diastolic BP Lifestyle No Compelling Indication Compelling Indication Classification (mm Hg) (mm Hg) Modification (Drug Therapy) (Drug Therapy)
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1157
PHARMACODYNAMICS
GOALS OF TREATMENT
1158
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1158
Barriers to Goal Achievement
RATIONAL DRUG SELECTION
Algorithm for Management of Hypertension Lifestyle Modifications
1159
60
50
40
30
20
10
0
SBP 120 SBP 180
10 -Y
ea r R
is k
of C
H D
(% )
Cholesterol 180 240 240 240 240 240 HDL 50 50 35 35 35 35 Smoking No No No Yes Yes Yes Diabetes No No No No Yes Yes LVH No No No No No Yes
Figure 40–2. Ten-year risk for CHD by SBP and presence of other risk factors. (Source: Adapted from Anderson, K., Wilson, P., Odell. P., & Kannel, W. [1991]. An updated coronary risk profile: A statement for health professionals. Circulation, 83, 356–362.)
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1159
Stepped Therapy
Initial Drug Therapy
1160
Table 40–2 Lifestyle Modifications
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1160
1161
Lifestyle modifications
Initial drug choices
Without compelling indications
With compelling indications
Not at goal blood pressure
Optimize dosages or add additional drugs until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
Not at goal blood pressure (<150/90 mm Hg) (<140/90 mm Hg for those with diabetes or 140/80 chronic kidney disease)
SPB 159 or DBP 90–99 mm Hg 150
Thiazide-type diuretics for most;
may consider ACEI, ARB, CCB, or combination
SPB >160 or DBP >100 mm Hg
2-drug combination for most (usually thiazide-type) diuretics
and ACEI, ARB, BB, or CCB
Drug(s) for compelling indication
Other antihypertensive drugs (other diuretics, ACEI, ARB, alpha blockers,
CCB as needed)
Figure 40–3. James et al. (2014). 2014 evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the eighth joint national committee (JNC-8). Journal of the American Medical Association. 311(5), 507- 520. doi: 10.1001/jama. 2013.284427
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1161
Stepping Up to Multiple Drugs
1162
Table 40–3 Clinical Trial and Guideline Basis for Compelling Indications for Individual Drug Classes
Recommended Drugs
Compelling Indication* Diuretic BB ACEI ARB CCB Aldo ANT Clinical Trial Basis†
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1162
1163
Table 40–4 Common Combinations of Antihypertensive Drugs
Combination* Fixed-Dose Combination (mg)† Brand Name
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1163
1164
Table 40–5 Drug Choice Based on Concomitant Disease States
Disease State Drug Choice
Compelling Indications Unless Contraindicated
May Have Favorable Effects on Comorbid Conditions
Stepping Down
Patient Variables
Children and Adolescents
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1164
1165
Table 40–5 Drug Choice Based on Concomitant Disease States—cont’d
Disease State Drug Choice
May Have Unfavorable Effects on Comorbid Conditions (May Be Used With Special Monitoring Unless Contraindicated)
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1165
Older Adults
1166
Table 40–6 Max Blood Pressure Readings in Children and Adolescents (mm Hg) by Height at 95th Percentile to Diagnose HTN
Age Girls Girls Boys Boys
50th Percentile 75th Percentile 50th Percentile 75th Percentile for Height for Height for Height for Height
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1166
Women
1167
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1167
1168
Table 40–7 Antihypertensives in Pregnancy
Acceptable Drug Comments
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1168
Racial and Ethnic Minorities
1169
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1169
Concomitant Diseases and Therapies
1170
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1170
1171
On The Horizon
Renal GFR values that incorporate cystatin C levels become more reliable and uncover renal impairment earlier than the standard measurements. This can dramatically increase the number of patients requiring renal dosing of medications (Inkler et al, 2012).
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1171
Surgery Patients
1172
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1172
Cost
MONITORING
OUTCOME EVALUATION
1173
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1173
Adherence Issues
PATIENT EDUCATION
1174
Table 40–8 Factors to Improve Adherence to Therapy
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1174
REFERENCES
1175
HYPERTENSION P ATIENT
EDUCATI ON
Related to the Overall Treatment Plan and Disease Process
■■ Pathophysiology of hypertension and its long-term effects on target organs
■■ Role of lifestyle modifications in improving prognosis and keeping the number and cost of required drugs down
■■ Importance of adherence to the treatment regimen
■■ Self-monitoring of blood pressure
■■ Indications of target organ damage
■■ Need for regular follow-up visits with the primary care provider
Specific to the Drug Therapy
■■ Reason for taking the drug(s) and the anticipated action of the drug(s) on the disease process
■■ Doses and schedules for taking the drug(s)
■■ Possible adverse reactions and what to do when they occur
■■ Coping mechanisms for complex and costly drug regimens
■■ Interaction between lifestyle modifications and these drugs
Reasons for Taking the Drug(s)
Patient education about specific drugs is provided in Chapters 14 and 16. Specific information related to hypertension includes the reasons for taking the drugs. Antihypertensive drugs are given to reduce mortality and decrease target organ damage. Some drugs do both; most do one or the other. The expectations should be clear about what the drugs can and cannot do. Hypertension is a chronic condition that rarely develops in a short space of time and is not likely to be corrected in a short space of time, if at all. Patients with hypertension must understand the lifelong nature of the dis- order and the need to incorporate the treatment regimen into their everyday lives. The risk of target organ damage must be discussed, but hope must be maintained, and the potential for a good quality of life with adequate treatment must be emphasized.
Drugs as Part of the Total Treatment Regimen
The total treatment regimen includes salt reduction and avoidance of excessive fluid intake. Diuretics reduce fluid volume and may interact with dietary sodium reduction, resulting in orthostatic hypotension (OH). Care should be taken not to reduce salt and fluid too quickly. Patients should be taught to report signs and symptoms of fluid volume deficit. Sodium reduction may lead some patients to seek salt substitutes that have potassium as part of their contents. For patients taking ACE inhibitors or ARBs, this choice can result in excessively high potassium levels. Such salt substitutes should be avoided. Nonsalt herbal seasoning is more appropriate.
Vasodilators can produce OH. Tell patients to rise slowly from a supine position to permit the body to redistribute body fluids.
Regular aerobic exercise such as walking or cycling can improve blood pressure control. Gradually increased, regular exercise may lead to improvement in blood pressure level and reduce the drug(s) needed.
Adherence Issues
Nonadherence with the treatment regimen may reduce life expectancy and affect the functioning of target organs. Health-care providers should be aware of the potential problem of nonadherence, discuss the importance of adherence at each follow-up visit, and assist patients in removing barriers to adherence, such as the complexity and cost of the treatment regimen and the presence of adverse reactions.
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1175
1176
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1176
1177
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1177
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1178
1179
CHAPTER 41
Marylou V. Robinson
T
THYROID HORMONE SYNTHESIS
THYROID HORMONE SYNTHESIS, 1179
THYROID FUNCTION TESTS, 1180
SCREENING, 1181
HYPERTHYROIDISM, 1182 Pathophysiology
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Lifestyle Management
Drug Therapy
Monitoring
Outcome Evaluation
Patient Education
SUBCLINICAL HYPERTHYROIDISM, 1188
HYPOTHYROIDISM, 1188 Pathophysiology
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Drug Therapy
Monitoring
Outcome Evaluation
Patient Education
SUBCLINICAL HYPOTHYROIDISM, 1193
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1179
THYROID FUNCTION TESTS
1180
Table 41–1 Drug Effects on Thyroid Function
Drug Effect on Thyroid Function
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1180
!
SCREENING
1181
Table 41–2 Adult Thyroid Function Tests
Values in Values in Test Normal Value Hyperthyroidism Hypothyroidism
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1181
HYPERTHYROIDISM
Pathophysiology
Ophthalmopathy
1182
Table 41–3 Systemic Effects of Hyperthyroidism
Body System Clinical Manifestation Underlying Mechanism
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1182
Myxedema
Pharmacodynamics
1183
Table 41–3 Systemic Effects of Hyperthyroidism—cont’d
Body System Clinical Manifestation Underlying Mechanism
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1183
Goals of Treatment
Rational Drug Selection
Lifestyle Management
Drug Therapy
Preoperative Preparation
Patient Variables
1184
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1184
1185
Subclinical hyperthyroidism
TSH and free T4 every 3–4 wk
Presence of atrial fibriliation, ischemic heart disease, CHF, or pronounced osteoporosis?
Consider treatment with antithyroid drugs.
Remeasure TSH every 3–6 mo for 1 yr and
then 6–12 mo.
Initial drug choice
Yes No
Euthyroid and stable Continue therapy and recheck at 6–12 mo.
Disease not under control or relapse Consult with endocrinologist.
Hyperthyroidism
Presence of pregnancy, ophthalmopathy, difficulty swallowing, or overt cardiac symptoms?
Consult with/refer to endocrinologist.
Increase dietary iodine intake and begin drug therapy based
on TSH, free T4, and WBC lab data.
Patients with short-term disorder (e.g., thyroiditis)— beta-adrenergic blockers,
aspirin, or NSAIDs Children—
Check with specialists for current RX
Patients with mild disease— propylthiouracil or methimazole
with beta-adrenergic blocker to control symptoms
Young or middle-aged— propylthiouracil or methimazole
with beta-adrenergic blocker to control symptoms
Graves’ disease without significant ophthalmopathy— propylthiouracil or methimazole
with beta-adrenergic blocker to control symptoms
Pregnant patients— Older adults and cardiac patients—
radioactive iodine; may be pretreated with propylthiouracil or methimazole
Yes No
Figure 41–1. Drug therapy algorithm: Hyperthyroidism.
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1185
Drug-Related Variables
Monitoring
1186
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1186
Outcome Evaluation
Patient Education
1187
HYPERTHYROIDISM PA TIENT
EDUCATI ON
Related to the Overall Treatment Plan and Disease Process
Understanding the pathophysiology of hyperthy- roidism and its prognosis
Role of iodine intake in thyroid hormone production
Importance of adherence to the treatment regimen Need to take the drug for at least 1 year Indications of relapse or complications that need to
be reported Importance of discussing pregnancy or the potential
for pregnancy with the primary care provider Need for regular follow-up visits with the primary
care provider
Specific to the Drug Therapy
Discussion of the reasons for taking the drug(s) and the anticipated action of the drug(s) on the dis- ease process. It is especially important to inform the patient that antithyroid drugs take 4 to 8 weeks to have a noticeable effect.
Doses and schedules for taking the drug(s) Possible adverse reactions and what to do when
they occur Patient education specific to antithyroid drugs is
provided in Chapter 21. Patient education specific to beta-adrenergic blockers
is provided in Chapter 14.
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1187
SUBCLINICAL HYPERTHYROIDISM
HYPOTHYROIDISM
Pathophysiology
Primary Disease
Secondary Disease
1188
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1188
Pharmacodynamics
Goals of Treatment
1189
Table 41–4 Systemic Effects of Hypothyroidism
Body System Clinical Manifestation Underlying Mechanism
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1189
Rational Drug Selection
Drug Therapy
Patient Variables
1190
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1190
1191
C lin
ic al
ly e
ut hy
ro id
bu t T
S H
s til
l e le
va te
d
P rim
ar y
hy po
th yr
oi di
sm
If po
ss ib
le , s
to p
al l d
ru gs
w ith
p ot
en tia
l a nt
ith yr
oi d
ef fe
ct s.
Yo un
g an
d ot
he rw
is e
he al
th y
In iti
at e
le vo
th yr
ox in
e 50
–1 00
m cg
d ai
ly.
C lin
ic al
ly a
nd la
b eu
th yr
oi d
C on
tin ue
c ur
re nt
d os
e an
d re
ch ec
k TS
H in
6 w
ee ks
.
If st
ill e
ut hy
ro id
, c on
tin ue
cu rr
en t d
os e
an d
re pe
at TS
H e
ve ry
6 –1
2 m
o.
If eu
th yr
oi d,
c on
tin ue
cu rr
en t d
os e
an d
re pe
at T
S H
e ve
ry 6–
12 m
o.
If st
ill h
yp ot
hy ro
id ,
in cr
ea se
in in
cr em
en ts
a bo
ve ;
re pe
at T
S H
in 4
–8 w
k. If
st ill
h yp
ot hy
ro id
, r ef
er to
e nd
oc rin
ol og
is t.
If eu
th yr
oi d,
co nt
in ue
c ur
re nt
do se
a nd
re pe
at TS
H e
ve ry
6 –1
2 m
o.
If TS
H s
til l
el ev
at ed
, r ef
er to
en do
cr in
ol og
is t.
C on
tin ue
c ur
re nt
d os
e an
d re
pe at
T S
H in
4 –8
w k.
In cr
ea se
d os
e by
2 5
m cg
/d ay
fo r >
50 y
r a nd
/o r k
no w
n ca
rd ia
c di
se as
e; in
cr ea
se d
os e
by 5
0 m
cg /d
ay fo
r y ou
ng an
d ot
he rw
is e
he al
th y;
c he
ck T
S H
in 4
–8 w
k.
C lin
ic al
ly h
yp ot
hy ro
id an
d TS
H s
til l e
le va
te d
>5 0
yr a
nd /o
r k no
w n
ca rd
ia c
di se
as e
In iti
at e
le vo
th yr
ox in
e 12
.5 –5
0 m
cg d
ai ly.
TS H
a nd
fr ee
T 4
le ve
ls
TS H
a nd
fr ee
T 4
in 4
w k
Fi g
u re
4 1–
2. D
ru g
th er
ap y
al go
rit hm
: H yp
ot hy
ro id
is m
.
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1191
Drug-Related Variables
Monitoring
1192
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1192
Outcome Evaluation
Patient Education
SUBCLINICAL HYPOTHYROIDISM
1193
HYPOTHYROIDISM PA TIENT
EDUCATI ON
Related to the Overall Treatment Plan and Disease Process
Understanding the pathophysiology of hypothy- roidism and its prognosis.
Role of iodine intake in thyroid hormone production. Importance of adherence to the treatment regimen. Length of time the drug will need to be taken. For
those with thyroiditis, this may be less than 12 months. For many with primary hypothy- roidism, the treatment will be lifelong. The patient should be informed not to stop taking the drug without first consulting the health-care provider.
Indications of relapse or complications that need to be reported.
Importance of discussing pregnancy or the poten- tial for pregnancy with the primary care provider.
Need to wear a medical identification bracelet stating that patient is taking thyroid hormone replace- ment and to inform any provider who sees him or her that this is the case. This is especially impor- tant if this provider prescribes any new drugs for the patient.
Need for regular follow-up visits with the primary care provider, which will include laboratory monitoring of thyroid function to determine the status of the hypothyroidism and any needed dosage adjust- ments of the drug therapy.
Specific to the Drug Therapy
Discussion of the reasons for taking the drug(s) and the anticipated action of the drug(s) on the disease process. It is especially important to inform the patient that thyroid hormone replacement may take 4 to 8 weeks to have a noticeable effect.
Doses and schedules for taking the drug(s). Possible adverse reactions (e.g., rapid heart rate,
cardiac arrhythmias, chest pain, insomnia, diarrhea, or heat intolerance) and what to do when they occur.
Additional patient education specific to thyroid hormones is provided in Chapter 21.
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1193
REFERENCES
1194
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1194
1195
CHAPTER 42
Anne Hedger
P
ADULT PATIENTS WITH PNEUMONIA
Pathophysiology
ADULT PATIENTS WITH PNEUMONIA, 1195 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
PEDIATRIC PATIENTS WITH PNEUMONIA, 1199 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1195
Goals of Treatment
Rational Drug Selection Clinical Guidelines
1196
Table 42–1 Community-Acquired Pneumonia: Common Pathogens by Age
Age Common Pathogens
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1196
1197
Patient presents with clinical findings of pneumonia
Previously healthy and no risk factors for drug-resistant S.pneumoniae (DRSP) infection
Presence of comorbidities, such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or drugs; use of antimicrobials within the previous 3 mo; or other risks for DRSP infection
Clinical improvement in 48–72 hr
Macrolide (azithromycin, clarithromycin, or
erythromycin)
OR
Doxycycline
A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin)
OR
A !-lactam plus a macrolide (High-dose amoxicillin or amoxicillin-
clavulanate preferred)
Consider resistance.
Broader spectrum antibiotic
Continue to monitor.
Yes No
Figure 42–1. Treatment algorithm: Outpatient treatment of adults with community-acquired pneumonia.
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1197
Dosing Regimen
Patient Variables
1198
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1198
Lifestyle Modifications
Monitoring
Outcome Evaluation
Patient Education
PEDIATRIC PATIENTS WITH PNEUMONIA
1199
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1199
Pathophysiology
Goals of Treatment
Rational Drug Selection Patient Variables
1200
CLINICAL PEARLS
Immunizations Pneumococcal vaccine is recommended for specific groups of patients. Pneumococcal conjugate (PCV13) is recommended universally for all infants as part of the routine infant series, for children aged 6 to 18 years with immunocompromising conditions (CDC, 2013) and for adults aged 19 years or older with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants (CDC, 2012a). All patients with chronic medical conditions who are at high risk for infec- tions should get a pneumococcal polysaccharide vaccine. Chronic medical conditions that warrant pneumococcal vaccination include chronic lung disease (including asthma); chronic cardiovascular diseases; diabetes mel- litus; chronic liver diseases, cirrhosis; chronic alcoholism; functional or anatomic asplenia; immunocompromising conditions (including chronic renal failure or nephrotic syndrome); and cochlear implants and cerebrospinal fluid leaks (ACIP Adult Immunization Work Group, 2013; ACIP Childhood/Adolescent Immunization Work Group, 2013).
The influenza vaccine is recommended that all per- sons older than age 6 months be vaccinated annually, including pregnant women.
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1200
1201
Table 42–2 ! Drugs Commonly Used: Community-Acquired Pneumonia
Drug Dose Length of Treatment Strengths Available Comments
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1201
1202
Table 42–2 ! Drugs Commonly Used: Community-Acquired Pneumonia—cont’d
Drug Dose Length of Treatment Strengths Available Comments
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1202
Monitoring
Outcome Evaluation
Patient Education
1203
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1203
REFERENCES
1204
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1204
1205
CHAPTER 43
Benjamin J. Miller
T
PATHOPHYSIOLOGY, 1206 Nicotine Delivery
Nicotinic Receptors
Nicotine Withdrawal Syndrome
GOALS OF TREATMENT, 1206
RATIONAL DRUG SELECTION, 1207 Nicotine Replacement Therapy
Antidepressants
Nicotinic Receptor Partial Agonists
Combination Therapy
Nonpharmacological Treatment of Nicotine Addiction
Patient Variables
MONITORING, 1212
OUTCOME EVALUATION, 1213
PATIENT EDUCATION, 1213 Educational Resources
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1205
PATHOPHYSIOLOGY
Nicotine Delivery
Nicotinic Receptors
Nicotine Withdrawal Syndrome
GOALS OF TREATMENT
1206
On The Horizon TOBACCO-CESSATION THERAPIES
The future looks promising for tobacco-cessation therapies. Currently, a sublingual form of nicotine replacement, in a 2 mg or 4 mg dose, is available in Europe and Canada. Scientists are also investigating the potential of a vaccine that stimulates antibodies that block nicotine receptors in the brain and will be used to prevent relapse in smokers who quit. A recent study examining nicotine vaccinations found the vaccines were safe and well tolerated; however, insufficient antibodies developed that would lead to a significant long-term effect on relapse prevention (Tonstad et al, 2013).
BOX 43–1 ELECTRONIC CIGARETTES
Electronic cigarettes or e-cigarettes are growing in popu- larity as an alternative to traditional tobacco use, with U.S. sales expected to exceed $1 billion in 2013. E-cigarettes are battery-operated devices that deliver nicotine via inhaled vapor, eliminating the harmful tars and carbon monoxide. At present, there is considerable controversy over the health implications of e-cigarettes, which has attracted the attention of the FDA and the CDC (Sutfin, McCoy, Morrell, Hoeppner, & Wolfson, 2013).
Because of the ability to regulate the nicotine content, there may be a role for e-cigarettes in nicotine replace- ment therapy and tobacco cessation. In a small study of 86 tobacco users, the use of 18 mg of nicotine resulted in a significant decrease in withdrawal symptoms com- pared to a control group (Dawkins, Turner, Hasna, & Soar, 2012). These data suggest there may be a future role for e-cigarettes; however, no evidence-based recommenda- tions can be made at this time. Further study of the potential toxic effects of e-cigarette chemicals is warranted before large scale studies occur.
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1206
RATIONAL DRUG SELECTION
Nicotine Replacement Therapy
Nicotine Gum
Nicotine Lozenge
1207
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1207
Nicotine Nasal Spray
1208
CLINICAL PEARL
Nicotine Gum Patients complain about the taste of the nicotine gum. Suggest that the patient try the flavored variety, which patients seem to tolerate better.
Nicotine Transdermal System
CLINICAL PEARL
Nicotine Patch Advise patients to dispose of used nicotine patches out of the reach of children or animals. Enough nicotine is left in a used patch to lead to toxic levels in a child or small animal.
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1208
1209
Table 43–1 ! Drugs Commonly Used: Smoking Cessation
Drug Strength Available Dosage Comments
Nicotine Gum
Nicotine Transdermal Patch
Nicotine Nasal Spray
Nicotine Inhaler
Nicotinic Receptor Partial Agonists
Antidepressant
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1209
Nicotine Inhaler
Antidepressants
Bupropion
Nicotinic Receptor Partial Agonists
1210
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1210
Alpha2 Adrenergic Agonists
Combination Therapy
Nonpharmacological Treatment of Nicotine Addiction
1211
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1211
Patient Variables Pregnant Women
Children
Adolescents
1212
CLINICAL PEARL
Constipation and Tobacco Cessation Many patients experience constipation during tobacco cessation as the stimulating effects of nicotine on the GI system are decreased. Increased dietary fiber, in- creased fluids, and use of a bulk-producing laxative (Metamucil or Citrucel) or osmotic laxative (Miralax) will help with this problem.
MONITORING
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1212
OUTCOME EVALUATION
PATIENT EDUCATION
Educational Resources
1213
BOX 43–2 NICOTINE POISONING
Nicotine poisoning is a concern if children or pets ingest nicotine replacement products. There has been a rise in nicotine poisonings since e-cigarettes have appeared on the market (Chatham-Stephens et al, 2014). Ingesting even a small amount of nicotine may be toxic to young children. Symptoms of nicotine poi- soning include nausea, vomiting, increased salivation, headache, and sweating. Seizures and respiratory fail- ure may occur (Toxnet, 2014). Treatment for nicotine poisoning for mild toxicity is supportive (IV fluids, ob- servation). Treatment for severe toxicity includes IV flu- ids, airway support, and mechanical ventilation, with atropine given for bradycardia or muscarinic signs (Toxnet, 2014).
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1213
1214
SMOKING CESSATION P ATIENT
EDUCATI ON
Related to the Overall Treatment Plan/Disease Process
■■ Education regarding the physical and psychological aspects of tobacco addiction
■■ Role of lifestyle modifications
■■ Importance of adherence to the treatment regimen
■■ Need for regular follow-up visits with the primary care provider
Specific to the Drug Therapy
■■ Doses and schedules for taking the drug
■■ Possible adverse effects and what to do if they occur
■■ Interactions between other treatment modalities and these drugs
Reasons for Taking the Drug(s)
These drugs are given to help a person stop smoking. The medications that are used for smoking cessation need to be used as prescribed; overuse or underuse will increase treatment failure or lead to adverse effects. The patient needs to under- stand the danger of nicotine toxicity, know the symptoms, and have clear instructions to cease the medication and notify the health-care provider. The patient must not smoke while using a nicotine replacement. Nicotine replacement products, even after they are used, can be toxic to children and to pets; therefore, all of the products need to be handled carefully and disposed of properly after use.
Drugs as Part of the Total Treatment Regimen
The total treatment regimen includes nonpharmacological strategies. Nonpharmacological strategies such as relaxation, acupuncture, massage, exercise, and group therapy should be discussed and patients encouraged to incorporate multiple strategies to help them be successful.
A weight gain of 5 to 8 lb is common during tobacco cessation. Patients need to avoid strict diets during tobacco cessa- tion and increase exercise during cessation treatment. After they have been tobacco-free for a few months, they can then work on weight reduction. Encouraging exercise during treatment will decrease the amount of weight gained.
Adherence Issues
Patients should know that having quit before and resumed their habit does not predict that they cannot be successful and that patients often quit for a while and then lapse 2 or 3 times before they succeed.
Many patients need external motivation to be successful at tobacco cessation. Identifying each patient’s motivation and reminding her or him of it at each visit will assist patients in refocusing their goals when they feel like giving up. Common motivators include the health of their children or spouse and their own health. Pointing out the cost savings of quitting smoking, which can add up to over $250 a month for a pack-a-day smoker in New York City, where cigarettes are $9.00 a pack, can also help patients focus on their goal. Have them place a photo of what they will buy with their savings in a prominent place (the refrigerator or bathroom mirror) as a reminder.
REFERENCES
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1214
1215
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1215
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1216
1217
CHAPTER 44
Theresa Granger
SEXUALLY TRANSMITTED INFECTIONS, 1217 Populations at Risk
STI as Precursor to Cancer
Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
VAGINITIS, 1231 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
T
SEXUALLY TRANSMITTED INFECTIONS
Populations at Risk
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1217
STI as Precursor to Cancer
Pathophysiology
1218
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1218
Goals of Treatment
Rational Drug Selection Guidelines
1219
Table 44–1 Differential Diagnosis of Vaginal Discharge
Discharge Disease/ Appearance Symptoms pH Diagnostic Tests Microscope Findings Syndrome
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1219
1220
Table 44–2 ! Drugs Commonly Used: Sexually Transmitted Infections
Pathogen First Choice Alternative Choice
Bacterial Pathogens
Viral Pathogens First Episode Recurring Episodes
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1220
1221
Table 44–2 ! Drugs Commonly Used: Sexually Transmitted Infections—cont’d
Pathogen First Choice Alternative Choice
Human Papillomavirus
Fungal Pathogen Intravaginal Oral
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1221
1222
Table 44–2 ! Drugs Commonly Used: Sexually Transmitted Infections—cont’d
Pathogen First Choice Alternative Choice
Pathogen PROTOZOAN PATHOGEN
ECTOPARASITIC PATHOGENS
First Choice Alternative Choice
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1222
1223
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1223
1224
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1224
1225
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1225
1226
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1226
1227
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1227
Special Treatment Situations
1228
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1228
1229
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1229
Monitoring
1230
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1230
Outcome Evaluation
Patient Education
VAGINITIS
Pathophysiology
Cytolytic Vaginosis
Atrophic Vaginitis
1231
BOX 44–1 VACCINE-PREVENTABLE SEXUALLY TRANSMITTED INFECTIONS
Many of the sexually transmitted infections are vaccine preventable (HAV, HBV, and HPV). Due to growing pub- lic health concerns, escalating costs of treatment, and lack of insurance, preventing infections is, in most cases, easier and less expensive than treatment. Whenever possible, patients should be educated early and often regarding the type of vaccines that they would be successful candidates to receive. Currently, there is no approved vaccine available for hepatitis C virus (HCV). Prophylaxis treatment after exposure to the virus has not been shown to be effective (CDC, 2010).
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1231
1232
SEXUALLY TRANSMITTED INFECTIONS
Related to the Overall Treatment Plan/Disease Process
■■ Importance of routine Pap smears in women and testicular self-examinations (TSE) in men
■■ Prevention of high-risk sexual behaviors
■■ Avoidance of sexual intercourse until the organism is either eradicated (bacterial) or under control (viral)
■■ Include immunization against selected STDs as part of treatment regimen
Specific to the Drug Therapy
■■ Many OTC products are available to treat symptoms.
■■ Douching is no longer recommended because of the potential for pelvic infection and destroying the normal flora of Lactobacillus.
■■ BV must be diagnosed and treated on the same day in patients suspected of being pregnant (BV may cause preterm labor).
■■ Importance of assessment of pregnancy status in all women of childbearing years before prescribing
■■ Choosing a generic agent that has daily or twice-daily dosing increases patient compliance with treatment.
Reasons for Taking the Drug(s)
■■ Prevention of serious complications such as PID and infertility
■■ Prevention of transmission of infection to the uninfected (public health issue)
■■ Prevention of dyspareunia, which affects normal sexual relations
Drugs as Part of the Total Treatment Regimen
■■ Importance of seeking treatment when symptoms appear
■■ Importance of culturing asymptomatic young persons (aged 15 to 24) every 6 months
Adherence Issues
■■ Importance of following the labeled instructions to totally eradicate the infection
■■ Importance of finishing the full course of antibiotics
■■ Importance of contacting the health-care provider if side effects or rash appears
■■ The potential for drug interactions (the macrolides with antifungal, systemic antifungals, and birth control pills)
PATIENT EDUCATI
ON
Toxic Shock Syndrome
Noninfectious Vaginal Conditions
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1232
Other Conditions
Goals of Treatment
1233
Table 44–3 Treatment for Noninfectious Vulvovaginal Conditions
Condition Drug Used Nondrug Treatment
Hormonal Changes (normal responses)
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1233
Rational Drug Selection Guidelines
Cost
Patient Variables
Drug Variables
Monitoring
Outcome Evaluation
Patient Education
1234
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1234
REFERENCES
1235
VAGINITIS P ATIENT
EDUCATI ON
Related to the Overall Treatment Plan/Disease Process
■■ Knowledge of many causes of vaginal irritation, ranging from allergy to inflammatory conditions associated with local and systemic disease
■■ Knowledge of the physiological changes in vaginal epithelium from age 12 to 50
■■ Hygiene issues such as types of clothing for underwear, wiping correctly, and emptying bladder before and after intercourse
Specific to the Drug Therapy
■■ Many OTC products that were previously under prescriptive authority are available to treat symptoms and are still efficacious.
■■ Douching is no longer recommended because of the potential for pelvic infection and its destruction of the normal flora of Lactobacillus.
Reasons for Taking the Drug(s)
■■ Prevention of dyspareunia, which affects normal sexual relations
■■ Control of miserable chronic conditions like lichen sclerosus
Drugs as Part of the Total Treatment Regimen
■■ Importance of seeking treatment when symptoms first appear to obtain the correct diagnosis
■■ Drug treatment early may prevent long-term morbidity (atrophy, sclerosis, and cancers).
Adherence Issues
■■ Importance of following the labeled instructions to totally eradicate the infection
■■ Importance of contacting the health-care provider if side effects or rash appears
■■ Potential for drug interactions (the macrolides with antifungal, systemic antifungals, and birth control pills)
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1236
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1236
1237
CHAPTER 45
Teri Moser Woo
OUTCOME EVALUATION, 1248
PATIENT EDUCATION, 1248
PREVENTION OF TUBERCULOSIS, 1248 Pathophysiology
Drug Therapy
Monitoring
Outcome Evaluation
Patient Education
T
PATHOPHYSIOLOGY, 1238
GOALS OF TREATMENT, 1238
RATIONAL DRUG SELECTION, 1239 Risk Stratification
Screening
Drug Therapy for Infectious Tuberculosis
Drug Therapy for Drug-Resistant Tuberculosis
Algorithm
Extrapulmonary Tuberculosis
Patient Variables
MONITORING, 1247 Adverse Reactions to the Medications
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1237
PATHOPHYSIOLOGY
GOALS OF TREATMENT
1238
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1238
RATIONAL DRUG SELECTION
Risk Stratification
Screening
Drug Therapy for Infectious Tuberculosis
1239
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1239
1240
Table 45–1 Drug Regimens for Culture-Positive Pulmonary Tuberculosis Caused by Drug-Susceptible Organisms
Initial Phase Continuation Phase Rating (Evidence)
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1240
Six-Month Regimen Nine-Month Regimen
1241
Table 45–2 ! Drugs Commonly Used: Tuberculosis
Doses*
First-Line Drugs
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1241
1242
Table 45–2 ! Drugs Commonly Used: Tuberculosis—cont’d Doses*
Second-Line Drugs
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1242
Drug Therapy for Drug-Resistant Tuberculosis
1243
Table 45–2 ! Drugs Commonly Used: Tuberculosis—cont’d Doses*
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1243
Algorithm
Extrapulmonary Tuberculosis
Patient Variables Pregnancy and Lactation
1244
BOX 45–1 DIRECTLY OBSERVED THERAPY
Directly observed therapy (DOT) reduces the risk of de- veloping drug resistance. In DOT, the patient is required to take all of the medication in front of a health-care or other service provider. The Centers for Disease Control and Prevention (CDC), the American Thoracic Society (ATS), and the World Health Organization (WHO) recommend the widespread or universal use of DOT in the treatment of TB. DOT has been demonstrated to ensure the highest degree of compliance with the medication regimen. Compliance with DOT can be in- creased in many ways, including convenient clinic times and locations and incentives such as food, clothing, bus or carfare money, and gifts.
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1244
Pediatric Patients
1245
2 mo culture negative
Cavitation on CXR
or Positive AFB
smear at 2 mo No cavitation
CavitationHigh clinicalsuspicion for active
tuberculosis No cavitation
on CXR and
Negative AFB smear at 2 mo
INH/RIF
INH/RIF
INH/RIF
INH/RIF
INH/RIF
INH/RIF/EMB*/PZA†
INH/RPT‡§
2 mo culture positive
0 1 2 3 4 6 9 Time (months)
Patients in whom tuberculosis is proved or strongly suspected should have treatment initiated with isoniazid, rifampin, pyrazinamide, and ethambutol for the initial 2 months. A repeat smear and culture should be performed when 2 months of treatment have been completed. If cavities were seen on the initial chest radiograph or the acid-fast smear is positive at completion of 2 months of treatment, the continuation phase of treatment should consist of isoniazid and rifampin daily or twice weekly for 4 months to complete a total of 6 months of treatment. If cavitation was present on the initial chest radiograph and the culture at the time of completion of 2 months of therapy is positive, the continuation phase should be lengthened to 7 months (total of 9 months of treatment). If the patient has HIV infection and the CD4+ cell count is <100/µL, the continuation phase should consist of daily or 3 times weekly isoniazid and rifampin. In HIV-uninfected patients having no cavitation on chest radiograph and negative acid-fast smears at completion of 2 months of treatment, the continuation phase may consist of either once weekly isoniazid and rifapentine, or daily or twice weekly isoniazid and rifampin, to complete a total of 6 months (bottom). Patients receiving isoniazid and rifapentine, and whose 2-month cultures are positive, should have treatment extended by an additional 3 months (total of 9 months). *EMB may be discontinued when results of drug susceptibility testing indicate no drug resistance. †PZA may be discontinued after it has been taken for 2 months (56 doses). ‡RPT should not be used in HIV-infected patients with tuberculosis or in patients with extrapulmonary tuberculosis. §Therapy should be extended to 9 months if 2-month culture is positive. CXR = chest radiograph; EMB = ethambutol; INH = isoniazid; PZA = pyrazinamide; RIF = rifampin; RPT = rifapen- tine.
Source: American Thoracic Society, CDC, and Infectious Diseases Society of America (2003). Treatment of Tuberculosis. MMWR, 52 (RR11), 1–77.
Figure 45–1. Treatment algorithm for TB.
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1245
1246
Table 45–3 Treatment of Tuberculosis in Infants, Children, and Adolescents
Disease Category Drug Therapy Comments
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1246
Newborn Infants
The HIV-Positive Patient
MONITORING
1247
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1247
Adverse Reactions to the Medications
OUTCOME EVALUATION
PATIENT EDUCATION
PREVENTION OF TUBERCULOSIS
1248
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1248
Pathophysiology
Drug Therapy
1249
Table 45–4 Latent TB Treatment Regimens
Dosing Total Number Drug Duration Schedule of Doses
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1249
Monitoring
Outcome Evaluation
1250
On The Horizon DRUGS IN THE PIPELINE
Significant TB drug research has been spawned by the Global Alliance for TB Drug Development, which was established in 2000 to address the need for new and better TB drug treat- ment (www.tballiance.org). Child-appropriate formulations of the standard four-drug therapy (isoniazid + rifampin + pyrazi- namide + ethambutol) are currently in development and un- dergoing phase I clinical trials, as current formulations require either crushing of tablets or cannot easily be measured in the mg/kg dose required for infants less than 5 kg. The following are currently in early phase II trials:
• A combination of bedaquiline, clofazamine, and PA-824 in a less than 4-month, all-oral regimen for MDR TB. PA-824 is a nitroimidazole, a novel antibacterial class.
• A combination of bedaquiline, pyrazinamide, and PA-824 in a less than 4-month, all-oral regimen for MDR TB.
• A combination of bedaquiline, clofazimine, pyrazinamide, and PA-824 in a less than 4-month, all-oral regimen for MDR TB.
• A combination of bedaquiline, clofazimine, and pyrazi- namide in a less than 4-month, all-oral regimen for MDR TB.
Late phase II trials include a combination of PA-824, moxi- floxacin, and pyrazinamide that is showing promise for curing TB and some forms of MDR TB in 4 months using an oral regi- men that can be administered in a fixed dose. Phase III trials include investigation of a combination of isoniazid, rifampin, pyrazinamide, and moxifloxacin that is demonstrating prom- ise in shortening the length of TB treatment from 6 months to 4 months. Another phase III trial is investigating a combina- tion of ethambutol, rifampin, pyrazinamide, and moxifloxacin in a 4-month regimen to treat TB.
The Global Alliance continues to focus funds and scientific energy toward developing drugs that simplify and shorten treatment regimens, are effective against MDR TB, are com- patible with antiretroviral therapies for HIV, and expand the pediatric formulations available.
Patient Education
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1250
REFERENCES
1251
TUBERCULOSIS P ATIENT
EDUCATI ON
Related to the Overall Treatment Plan and Disease Process
■■ A clear description of the pathophysiology and mode of transmission of TB: patients need to understand that they can be infectious to their close contacts if they do not receive adequate treatment.
■■ A thorough outline of the complete treatment regimen, including an estimated length of time for treatment: patients need to know up front that they will be receiving months and possibly more than a year of treatment.
■■ Importance of adherence to the treatment regimen.
■■ Importance of regularly scheduled follow-up appointments.
Specific to the Drug Therapy
■■ A written plan of the medication schedule is essential, especially with multidrug regimens.
■■ Possible adverse effects of the medications and the importance of reporting immediately to the health-care provider any vague, flu-like symptoms.
Reasons for Taking the Drug(s)
■■ The drugs are given to prevent or eliminate infection by M. tuberculosis.
Drugs as Part of the Total Treatment Regimen
Tuberculosis medications are a part of the total treatment regimen, which also includes strict pulmonary care.
Adherence Issues
Extensive patient education is essential to successful treatment. The patient must understand the purpose for the long, multidrug treatment regimen and be a partner in the treatment. Adherence is a major issue; therefore, all teaching should have the underlying theme of taking all medication as scheduled. The long period of treatment requires education that is repeated and reviewed at the monthly visits. To teach patients who may be illiterate or who understand English only mini- mally, education should be conducted in a variety of media, such as videos in the patient’s primary language. Peer health counselors may also help to educate patients with TB. DOT may enhance compliance with and adherence to therapy.
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1252
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1252
1253
CHAPTER 46
Teri Moser Woo
VIRAL UPPER RESPIRATORY INFECTION, 1253 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
SINUSITIS, 1256 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
OTITIS MEDIA, 1259 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
OTITIS EXTERNA, 1264 Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
U
VIRAL UPPER RESPIRATORY INFECTION
3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1253
Pathophysiology
Goals of Treatment
Rational Drug Selection Drug Therapy
1254
Table 46–1 ! Drugs Commonly Used: Viral Upper Respiratory Infections
Drug Adult Dose Pediatric Dose Strengths Available Comments
Oral Decongestants
Topical Decongestants
3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1254
Nonpharmacological Therapy
Monitoring
Outcome Evaluation
Patient Education
1255
3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1255
SINUSITIS
Pathophysiology
1256
CLINICAL PEARL
Nutritional or herbal therapy Nutritional or herbal therapy is often thought to de- crease symptoms of the common cold. In the 1970s, Linus Pauling first brought forward the idea that vitamin C prevents and alleviates episodes of the common cold. Although this has still not been scientifically proven, many patients continue to take vitamin C at the first sign of a cold.
Zinc lozenges have also been proposed as a treat- ment for the common cold. It is thought that zinc ions inhibit rhinovirus replication in vitro. In a systematic re- view of seven randomized controlled trials (RCTs) (754 patients total), two of the studies suggested reduced duration and severity of upper respiratory infection (URI) symptoms (Marshall, 2000). Another review of 14 placebo-controlled trials published from 1966 to 2000 found that one well-designed study showed im- provement with the use of zinc nasal gel (Caruso, Prober, & Gwaltney, 2007). In a more recent RCT, a group of patients took a 13.3 mg zinc lozenge every 2 to 3 hours while awake and had a significantly shorter duration of cold symptoms (4.0 days versus 7.1 days; P less than 0.0001), shorter duration of cough (2.1 days versus 5.0 days), and nasal discharge (3.0 versus 4.5 days) than did the placebo control group (Prasad, Beck, Bao, Snell, & Fitzgerald, 2008). In light of these studies, zinc lozenges may decrease URI symptoms in some patients. Zinc nasal gels (Zicam) should be avoided after reports of permanent anosmia and an FDA warning to avoid their use.
Another common herbal therapy that patients may be using for their cold symptoms is echinacea. Echi- nacea is widely used in Europe for the prevention and treatment of colds and flu. Its use is increasing in the United States. A number of European studies have demonstrated the immune-enhancing properties of echinacea, specifically increasing T-cell activity and in- terferon. Among European providers, echinacea is the leading herbal recommendation for the prevention of colds and flu. It is available in tablet, liquid, and tea bag form. The correct dosage is 900 mg daily divided into two or three doses, or 40 drops of the juice 3 times a day. Length of therapy should not exceed 8 weeks. There are no reported side effects at the recommended dosages. It appears to be safe during pregnancy and lactation. The only true contraindication is having a pro- gressive systemic disease such as tuberculosis or mul- tiple sclerosis or an autoimmune illness. Echinacea is a relative of the daisy; therefore, patients who are allergic to daisies should also avoid any form of echinacea.
3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1256
Goals of Treatment
Rational Drug Selection
1257
Table 46–2 ! Drugs Commonly Used: Sinusitis and Otitis Media
Length of Drug Dose Treatment Strengths Available Comments
3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1257
1258
Table 46–2 ! Drugs Commonly Used: Sinusitis and Otitis Media—cont’d
Length of Drug Dose Treatment Strengths Available Comments
Monitoring
Outcome Evaluation
Patient Education
3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1258
OTITIS MEDIA
1259
Common cold or allergic rhinitis, which develops purulent nasal discharge
No
Improvement
Treat for 5–7 days (10 days in children)
Refer to otolaryngologist
Worsening or no improvement
after 3 days
Treat for 7–10 days (10 days in children)
Improvement
Yes
• Symptoms persistent and not improving for ≥10 days
• Severe symptoms for 3–4 days • “Double sickening” or worsening
of symptoms after 3–4 days
Initiate antibiotic treatment with first line treatment:
amoxicillin OR
amoxicillin-clavulanate OR
beta lactamase cephalosporin
Initiate treatment with second-line antibiotic: amoxicillin-clavulanate
OR beta lactamase stable cephalosporin
OR respiratory fluoroquinolone (adults)
Worsening or no improvement
after 3 days
• Age < 2 years • Daycare attendance • Antibiotics in past month • Comorbidities • Immunocompromised • Hospitalized in past 5 days
At risk for resistance?
Figure 46–1. Algorithm for treatment of sinusitis.
3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1259
Pathophysiology
Goals of Treatment
Rational Drug Selection Guidelines
1260
3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1260
Antimicrobial Resistance
Dosing Regimen
Length of Treatment
Watchful Waiting (No Antibiotics)
1261
3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1261
Pain Relief
1262
Child presents with confirmed diagnoses of AOM.
Age >2 yr with nonsevere illness, or uncertain diagnosis
Observe for 48–72 h with assurance of
appropriate follow-up.
Age < 2 yr and certain diagnosis or older child
with severe illness
Follow up patient 3–4 wk.
Begin appropriate antimicrobial therapy.
Does child have fever >39°C or severe otalgia?
Improvement after observation period
Yes No
Patient follow-up on completion of
antibiotics (3–4 wk)
Reassess and confirm diagnosis AOM, change
antimicrobial therapy (see Table 47–2)
Yes No
Amoxicillin/clavulanate 90 mg/kg/day of amoxicillin or appropriate alternative
for penicillin-allergic patient (see Table 47–2)
Amoxicillin 80–90 mg/kg/day is first-choice antibacterial.
Patient responds to initial treatment.
Yes No
Length of treatment < 2 years: 10 days
2–5 years (mild/moderate AOM): 7 days >6 years (mild/moderate AOM): 5–7 days
Figure 46–2. Algorithm for treatment of AOM.
3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1262
1263
Table 46–3 Treatment Options for Otitis Media
Temperature >39°C Antibiotic Treatment (102.2°F) and Severe Alternative Treatment After 48–72 h of Failure of Initial Otalgia; or <age 2 years Initial Treatment (if Penicillin Allergy) Antibiotic Treatment
Monitoring
Outcome Evaluation
Patient Education
3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1263
OTITIS EXTERNA
Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
REFERENCES
1264
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1265
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1267
CHAPTER 47
Erin Anderson
U PATHOPHYSIOLOGY
Host Factors Anatomy and Physiology of the Genitourinary Tract
PATHOPHYSIOLOGY, 1267 Host Factors
Microbial Factors
PHARMACODYNAMICS, 1269
GOALS OF TREATMENT, 1270
RATIONAL DRUG SELECTION, 1270 Algorithm
Drug Therapy
Drug Variables
Patient Variables
MONITORING, 1276
OUTCOME EVALUATION, 1277
PATIENT EDUCATION, 1278 Lifestyle Management
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1267
Behavioral Factors
Microbial Factors Ability of the Bacteria to Adhere to Epithelial Cells
Virulence of the Organism
Ability of the Organism to Survive the Urinary Tract Environment
Inflammatory Reaction to Bacteria
1268
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1268
PHARMACODYNAMICS
1269
Table 47–1 Factors Associated With Urinary Tract Infections
Host Factors Microbial Factors Inconsistent or Not Associated Factors
Table 47–2 Urinary Tract Infection Symptoms by Age
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GOALS OF TREATMENT
RATIONAL DRUG SELECTION
Algorithm
Drug Therapy
Drug Variables Spectrum of Activity
1270
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1270
Potential Adverse Drug Reactions
1271
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1271
Resistance Patterns
Cost
1272
Table 47–3 ! Drugs Commonly Used: Upper and Lower Urinary Tract Infections
Indication Primary Choices Alternative Choices
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1272
Patient Variables Age
1273
Table 47–3 ! Drugs Commonly Used: Upper and Lower Urinary Tract Infections—cont’d
Indication Primary Choices Alternative Choices
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1274
Dysuria, frequency, urgency, and no complicating factors
Suspect vaginitis/STD
Pelvic exam, urine and vaginal cultures
Vaginitis (see Chapter 44)
Asymptomatic after 3 days of therapy
Asymptomatic Symptomatic
No further follow-up
Positive culture
Post-treatment UA and culture ?Upper UTI
Treatment for 14 days Posttreatment UA and culture
Check adherence and lifestyle. Check sensitivities; may change antimicrobial
based on culture or extend therapy for 7–10 days.
Negative culture (”sterile pyuria”)
If symptoms persist >2 weeks, consult/refer for work-up.
?Chlamydia (see Table 47–3)
Culture urine
Symptomatic after 3 days of therapy
STD (see Chapter 44 )
+ UA/UTI – UA
Begin antimicrobial therapy (see Table 47–3).
Teach lifestyle management.
Work-up for other diagnosis
Suspect lower UTI
Urinalysis
Figure 47–1. Treatment protocol: Urinary tract infections in women.
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1274
Male Gender
Pregnancy
1275
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1275
Underlying Cause
MONITORING
1276
Urinary tract infection confirmed by urinalysis and culture
Complicated
Inpatient with IV antibiotics
Repeat culture in 48 h.
Refer to urologist.
Ultrasound before discharge
VUR+
VUR
Urine sterile, asymptomatic
Complete antimicrobial therapy.
Urine not sterile, symptomatic
If urine not sterile, refer to urologist.
Check antibiotic used against sensitivities.
Ultrasound in <10 days if: male, female <36 months or febrile UTI
in females age 3–7 yr with a fever >38.5°
Repeat culture after 48 h of antibiotic therapy.
Repeat culture after 48 h of antibiotic therapy.
If urine not sterile, continue therapy to 14 days and reculture 24–48 h after completion of therapy.
Organism sensitive Organism not sensitive
Antibiotic therapy for 7–14 days (see Table 47–3) Teach lifestyle management, including toileting habits.
Continue antibiotic for 14 days. Work-up for complications
Change antibiotic and give new drug for 14 days.
Recurrent UTI (>2/yr)
Start prophylactic drug for 6 mo.
UTI No UTI
Change drug for prophylaxis.
Discontinue drug and monitor.
Uncomplicated
Outpatient with oral or IM antibiotics
Figure 47–2. Treatment protocol: Urinary tract infections in children.
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1276
OUTCOME EVALUATION
1277
Dysuria, frequency, urgency
+ UA and culture/UTI + UA and + for prostatitis + only for prostatitis
(Not covered here)
– UA and culture
Refer for work-up.
Reculture in 72 h.
Reculture in 72 h.
Suspect STD. Culture any urethral discharge.
Urine for gonorrhea/clamydia NAAT (see Chapter 44)
Begin antimicrobial therapy (may begin empiric with
trimethoprim-sulfamethoxazole, but will need to adjust based on culture).
Suspect prostatitis. Three-void urine specimen for
urinalysis and culture
Choose antimicrobial that covers both common UTI organisms and prostatitis.
Suspect UTI. Urinalysis and urine culture
Urine sterile/asymptomatic
Complete antimicrobial therapy.
Change antimicrobial if needed based on culture.
May require 6–12 wk of antimicrobial therapy.
Consider referral for work-up.
Urine not sterile/symptomatic
Urine not sterile
Figure 47–3. Treatment protocol: Urinary tract infections in men.
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1277
PATIENT EDUCATION
Lifestyle Management
1278
URINARY TRACT INFECTIONS P ATIENT
EDUCATI ON
Related to the Overall Treatment Plan or Disease Process
■■ Understanding the causes of UTIs and their prognoses.
■■ Role of lifestyle modifications in preventing UTIs, especially ingestion of cranberry juice or cranberry extract; avoidance of diaphragms and spermicides, especially those containing nonoxynol-9; voiding 10 to 15 minutes after sexual intercourse to wash out the bacteria from the urethra that may have entered the bladder during intercourse; maintaining fluid intake of at least 2,000 mL/d of noncaffeinated fluids; and not resisting the urge to void.
■■ Importance of adherence to the treatment regimen.
■■ Indications of relapse or complications that need to be reported.
■■ Need for a follow-up visit only if patient remains symptomatic.
Specific to the Drug Therapy
■■ Discussion of the reasons for taking the drug(s) and the anticipated action of the drug(s) on the disease process. The patient should be asymptomatic within 48 hours for simple, uncomplicated lower UTIs and within 7 days for upper UTIs. Urinary analgesics should relieve symptoms within 24 hours.
■■ Doses and schedules for taking the drug and the length of time the drug will need to be taken. Possible adverse reactions and what to do when they occur. For patients given phenazopyridine, warn them that the drug turns the urine bright orange and that this is not an indication of hematuria.
■■ Additional patient education specific to antimicrobials is provided in Chapter 24.
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REFERENCES
1279
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1279
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1280
UNIT IV
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3827_Ch48_1281-1302 01/07/15 3:23 PM Page 1282
1283
CHAPTER 48
Priscilla M. Nodine
PHARMACOKINETICS AND PHARMACODYNAMICS IN WOMEN, 1285 Pharmacokinetics
Pharmacodynamics
FACTORS THAT INFLUENCE MEDICATION ADMINISTRATION, 1287 Puberty
Pregnancy
Menopause
Older Age
FACTORS THAT INFLUENCE POSITIVE OUTCOMES, 1292 Number of Drugs Taken
Duration of Medication Therapy
Fear That Medications Cause Disease
Nutritional Status
Safety of Medications While Breastfeeding
Ethnic, Cultural, and Religious Differences
COMMON PROBLEMS THAT REQUIRE MEDICATIONS, 1293 Menopause
Dysmenorrhea, Premenstrual Syndrome, and Premenstrual Dysphoric Disorder
Endometriosis
HIV/AIDS in Pregnancy
Infertility
Polycystic Ovarian Syndrome
HEALTH PROMOTION, DISEASE PREVENTION, AND SCREENING, 1298
GAY AND LESBIAN HEALTH, 1298
D
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1284
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1284
PHARMACOKINETICS AND PHARMACODYNAMICS IN WOMEN
Pharmacokinetics
1285
Table 48–1 Gender Differences in Pharmacokinetic Parameters
Pharmacokinetic Parameter Sex-Based Difference
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1285
Pharmacodynamics
1286
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1286
FACTORS THAT INFLUENCE MEDICATION ADMINISTRATION
Puberty
1287
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1287
Pregnancy
1288
CLINICAL PEARL
Prescribing for adolescents State laws vary regarding consent for treatment of sex- ually transmitted infections, contraception, and medical record confidentiality in minor patients. Nurse practi- tioners should become familiar with what health-care services can be provided to minors without parental consent.
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1288
1289
Table 48–2 Use of Selected Herbs During Pregnancy
Common Name Comments
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1289
Menopause
1290
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1290
1291
Table 48–3 Alternative Therapies for Menopause Symptoms
Symptom Alternative Therapy and Its Effects
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1291
Older Age
FACTORS THAT INFLUENCE POSITIVE OUTCOMES
Number of Drugs Taken
Duration of Medication Therapy
Fear That Medications Cause Disease
Nutritional Status
1292
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1292
Safety of Medications While Breastfeeding
Ethnic, Cultural, and Religious Differences
COMMON PROBLEMS THAT REQUIRE MEDICATIONS
Menopause
1293
CLINICAL PEARL
Prescribing in pregnancy and lactation The pregnancy risk categories (A, B, C, D, X) should be used as a guide only. Category X (known teratogenic effects on the fetus) must be avoided in pregnancy. Cat- egory D drugs should be used only in a life-threatening situation (i.e., chemotherapy drugs), as known fetal risks exist. Categories A, B, and C may have some risks. Every prescription drug now provides “Pregnancy Implications” and “Lactation” labeling and these should be read and understood before prescribing.
In 2014 the Food and Drug Administration passed The Pregnancy and Lactation Labeling Rule that will af- fect all prescription drugs and biological products. The pregnancy risk categories (A, B, C, D, X) will be elimi- nated and replaced with a summary of risks of using the drug during pregnancy and while breastfeeding. There will be a new section on drug labels titled “Female and Male of Reproductive Potential” that will include information about the need for pregnancy test- ing, contraceptive recommendations, and drug effects on fertility. All new drugs approved after June 30, 2015, will have the new labeling format (with no A, B, C, D, or X). The new format will be phased in gradually for previously approved drugs.
CLINICAL PEARL
Prescribing in a diverse culture Be aware of the common ethnic groups in your patient population. Get to know the cultures. Frequently, com- munity programs that teach cultural awareness and some simple ethnic phrases are available for health-care personnel. Bookstores carry pocket-sized books to facil- itate a simple medical interview in different languages.
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1293
Dysmenorrhea, Premenstrual Syndrome, and Premenstrual Dysphoric Disorder
Dysmenorrhea
1294
CLINICAL PEARL
Progesterone-only therapies Women who have contraindications to estrogen use need to be counseled that there are several easy-to-use progesterone methods, without estrogen, that offer effective contraception and treatment for dysmenorrhea.
Premenstrual Syndrome (PMS)
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1294
Premenstrual Dysphoric Disorder
Pathophysiology
Treatments
Nutritional Supplements
1295
Table 48–4 Treatment Options for PMDD
Therapy Dosing Symptom Improvement
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1295
Herbals
Drug Therapies
Psychotherapeutics
Endometriosis
1296
Table 48–4 Treatment Options for PMDD—cont’d
Therapy Dosing Symptom Improvement
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Pathophysiology
Drug Therapies
HIV/AIDS in Pregnancy
1297
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1297
Infertility
Polycystic Ovarian Syndrome
HEALTH PROMOTION, DISEASE PREVENTION, AND SCREENING
GAY AND LESBIAN HEALTH
1298
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1298
REFERENCES
1299
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1299
1300
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1300
1301
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1301
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1302
1303
CHAPTER 49
James Raper
HYPOGONADISM, 1304 Pathophysiology
Classifications
Signs and Symptoms of Hypogonadism Across the Life Span
Older Men
Diagnosis
TESTOSTERONE REPLACEMENT THERAPY, 1307 Pharmacodynamics
Testosterone Clinical Use and Dosing
COMMON PROBLEMS THAT REQUIRE MEDICATIONS, 1312 Erectile Dysfunction
Benign Prostatic Hyperplasia
Prostatitis and Male Pelvic Pain Syndrome
Hair Loss
HEALTH PROMOTION, DISEASE PREVENTION, AND SCREENING IN MEN, 1315
ETHNIC AND RACIAL ISSUES, 1315
HEALTH ISSUES FOR MEN WHO HAVE SEX WITH MEN, 1316 HIV Infection and Sexually Transmitted Infections
Anal Cancer
Tobacco Abuse
CONCLUSION, 1317
G
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1303
HYPOGONADISM
Pathophysiology
Classifications
1304
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1304
Signs and Symptoms of Hypogonadism Across the Life Span
1305
Dihydrotestosterone (DHT) Estradiol (E2)
• Muscle mass • Sexual function • Skeletal growth • Spermatogenesis
• Bone formation • Breast tissue
• Acne • Alopecia • Facial and body hair • Prostate growth
Testosterone
Figure 49–1. Effects of testosterone and its metabolites in men.
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1305
1306
BOX 49–1 COMMON CAUSES OF PRIMARY AND SECONDARY HYPOGONADISM
Primary Hypogonadism
Cancer treatment. Chemotherapy or radiation therapy for the treatment of cancer can interfere with testosterone and sperm production. The effects of both treatments are often temporary, but permanent infertility may occur. Although many men regain their fertility within a few months after treatment ends, preserving sperm before starting cancer therapy is a consideration.
Hemochromatosis. Excess iron in the blood can cause testicular failure or pituitary gland dysfunction, affecting testos- terone production.
Klinefelter syndrome. In this congenital abnormality of the sex chromosomes, X and Y, a male has two or more X chro- mosomes in addition to one Y chromosome. The Y chromosome contains the genetic material that determines the sex of a child and related development. In addition to other defects, the extra X chromosome causes abnormal development of the testicles, which in turn results in underproduction of testosterone.
Mumps orchitis. If a mumps infection involving the testicles (mumps orchitis) occurs during adolescence or adult- hood, long-term testicular damage may occur. This may affect normal testicular function and testosterone production.
Normal aging. As men age, testosterone production slowly and continuously decreases. The rate of decline varies greatly among men. As many as 30% of men older than 75 years have a low testosterone level, according to the American Association of Clinical Endocrinologists. The value of treatment is controversial.
Trauma to the testicles. The testicles are prone to injury. Damage to normally developed testicles can cause hypogo- nadism. Damage to one testicle may not impair testosterone production.
Undescended testicles. Before birth, the testicles develop inside the abdomen and normally move down into their permanent place in the scrotum. Sometimes, one or both of the testicles do not descend at birth. This condition often corrects itself within the first few years of life without treatment. If not corrected in early childhood, it may lead to malfunction of the testicles and reduced production of testosterone.
Secondary Hypogonadism
HIV/AIDS. This virus can cause low levels of testosterone by affecting the hypothalamus, the pituitary, and the testes.
Inflammatory disease. Certain inflammatory diseases, such as sarcoidosis, histiocytosis, and tuberculosis, involve the hypothalamus and pituitary gland and can decrease testosterone production.
Kallmann syndrome. Abnormal development of the hypothalamus can cause hypogonadism. This abnormality is also associated with impaired development of the ability to smell (anosmia).
Medications. Certain drugs and some hormones can affect testosterone production. Obesity. Being significantly overweight at any age may be linked to hypogonadism. Opioid users. Commonly prescribed opioids in sustained-action dosage forms usually produce subnormal sex hormone
levels, which may contribute to a diminished quality of life for many patients with painful chronic illness. Pituitary disorders. An abnormality in the pituitary gland can impair the release of hormones from the pituitary gland to
the testicles, affecting normal testosterone production. A pituitary tumor or other type of brain tumor located near the pituitary gland may cause testosterone or other hormone deficiencies. Surgery or radiation therapy for the treatment of brain tumor may impair pituitary function and cause hypogonadism.
Older Men
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Diagnosis
TESTOSTERONE REPLACEMENT THERAPY
Pharmacodynamics
Anemia
Bone Mineral Density
1307
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1307
1308
Table 49–1 Postpubertal Hypogonadal-Related Problems and Effectiveness of Testosterone Replacement
Postpubertal Problems Associated With Hypogonadism Evidence of Improvement With Administration of Testosterone
Cognitive Function Lower Urinary Tract Symptoms
Metabolic Syndrome and Type 2 Diabetes
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1308
Cardiovascular Disease
Mood and Energy and Quality of Life
Muscle Mass and Strength
1309
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1309
Sexual Desire, Function, and Performance
Testosterone Clinical Use and Dosing
1310
Table 49–2 ! Testosterone Preparations Available in the United States for Replacement in the Hypogonadal Male
Drug Dose
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1310
Risks and Contraindications Drug-Drug Interactions
Monitoring
1311
Table 49–3 Comparison of Testosterone Replacement Therapies
Topical Gels Buccal Intramuscular Subcutaneous & Liquids Topical Patch
Convenience
Cost
Physiological
Side effects
Stigma
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1311
Patient Education
COMMON PROBLEMS THAT REQUIRE MEDICATIONS
Erectile Dysfunction
Pathophysiology
Phosphodiesterase Type 5 (PDE-5) Inhibitors
1312
Table 49–4 Contraindications and Associated Potential Risk for Testosterone Replacement Therapy
Contraindication Parameter vs. Potential Risk
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1312
1313
Table 49–5 " Dosing Schedule of PDE-5 Inhibitors
Drug Name How Supplied Dose
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1313
Benign Prostatic Hyperplasia
Prostatitis and Male Pelvic Pain Syndrome
Hair Loss
1314
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1314
HEALTH PROMOTION, DISEASE PREVENTION, AND SCREENING IN MEN
ETHNIC AND RACIAL ISSUES
1315
Table 49–6 Screening Tests and Immunization Guidelines for Men by Age
Screening Tests Ages 18–39 Ages 40–49 Ages 50–64 Ages 65 and Older
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1315
HEALTH ISSUES FOR MEN WHO HAVE SEX WITH MEN
HIV Infection and Sexually Transmitted Infections
1316
Table 49–6 Screening Tests and Immunization Guidelines for Men by Age—cont’d
Screening Tests Ages 18–39 Ages 40–49 Ages 50–64 Ages 65 and Older
Immunizations
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1316
Anal Cancer
Tobacco Abuse
CONCLUSION
REFERENCES
1317
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1317
1318
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1318
1319
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1319
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1320
1321
CHAPTER 50
Teri Moser Woo
HISTORICAL PERSPECTIVE ON PEDIATRIC PRESCRIBING, 1321 Federal Drug Regulation
Best Pharmaceuticals for Children Act
PHARMACOKINETIC AND PHARMACODYNAMIC DIFFERENCES IN CHILDREN, 1322 Pharmacokinetics
Pharmacodynamics
DEVELOPMENTAL ASPECTS OF PEDIATRIC MEDICATION ADMINISTRATION, 1325 Breastfed Infants
Infants
Toddlers and Preschoolers
School-Age Children
Adolescents
FACTORS THAT INFLUENCE POSITIVE OUTCOMES, 1331 Specific Factors That Influence Compliance
Improving Compliance in the Pediatric Patient
Childhood Obesity Influences Outcomes
P
HISTORICAL PERSPECTIVE ON PEDIATRIC PRESCRIBING
Federal Drug Regulation
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1321
Best Pharmaceuticals for Children Act
1322
PHARMACOKINETIC AND PHARMACODYNAMIC DIFFERENCES IN CHILDREN
Pharmacokinetics
The Pediatric Trials Network is funded by the Best Pharmaceuticals for Children Act via the Eunice Shriver National Institute of Child Health and Human Develop- ment (NICHD). The purpose of the Pediatric Trials Net- work (PTN) is to create an infrastructure to study critical drugs and diagnostic devices in children to improve labeling for pediatric use. The PTN will conduct 16 tri- als over the next 5 years, adding to critical information on pediatric drug safety and efficacy. For more informa- tion see PTN’s website, www.pediatrictrials.org.
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1322
Drug Absorption
Distribution
Metabolism
1323
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1323
1324
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1324
Excretion
Pharmacodynamics
DEVELOPMENTAL ASPECTS OF PEDIATRIC MEDICATION ADMINISTRATION
Breastfed Infants
1325
BOX 50–1 PRESCRIBING TO LACTATING WOMEN
Prescribing medications for lactating women should be undertaken with the same caution as prescribing for pregnant women. Assume that any drug prescribed will, in some amount, be found in the breast milk. Therefore, knowledge regarding safety of medications for lactating women is essential for all primary care practitioners. When prescribing, take the following steps:
1. Review the safety of the drug during lactation. 2. If the drug is relatively safe, discuss the risks with the mother and explain the symptoms of drug toxicity. 3. Explain that the drug should be taken just after nursing or before infant’s sleep. 4. Measure drug concentrations in milk or infant’s serum when toxicity is likely. 5. Monitor the infant for signs of pharmacological action or drug toxicity. 6. Report any symptoms or signs of drug toxicity to the American Academy of Pediatrics, Committee on Drugs.
A few medications are absolutely contraindicated in lactating women (see Table 50-1). Contraindications include anti- neoplastic drugs because of immediate or delayed toxicity in the infant. Weekly use of methotrexate for rheumatic disease is acceptable during lactation, but the infant needs to be monitored closely, with routine laboratory analysis of complete blood count with differential, liver enzymes, and renal function essential to infant safety. Another contraindication to breastfeeding
Continued
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1325
Drug Excretion in Breast Milk
Factors Influencing an Infant’s Exposure to Drugs in Breast Milk
1326
BOX 50–1 PRESCRIBING TO LACTATING WOMEN—cont’d
is iodine-containing radioactive medications used in nuclear medicine studies. In this case, temporary cessation of breast- feeding (“pump and dump”) is indicated. The length of time before resumption of breastfeeding is determined by the half-life of the radiopharmaceutical agent.
Drugs that should be avoided include lithium and oral contraceptives, yet both have been used in lactating women. Lithium is excreted in breast milk at about 40% of the concentration of maternal serum, and milk and infant serum levels are approximately equal. If, for maternal health reasons, lithium needs to be prescribed, the infant’s serum lithium level needs to be monitored closely. The main contraindication to oral contraceptives containing estrogen is that they may decrease milk supply. An oral contraceptive with low estrogen levels can be prescribed once the milk supply is well established (more than 6 weeks’ postpartum), but the first choice should be a progestin-only oral contraceptive. Decreased milk supply should be discussed with the mother as an adverse effect of estrogen-containing oral contraceptives prior to prescribing.
All illicit drugs are contraindicated in lactating women, specifically cocaine, heroin, and methamphetamine. Infants exposed to cocaine via breast milk may show signs of toxicity (irritability, tremors, increased startle response). Cocaine metabolites can be found in breast milk for up to 36 hours after the mother’s last dose. Heroin enters breast milk and can cause neonatal depression. Amphetamines are excreted in breast milk and cause excitation in the infant. Methamphetamine poses an additional concern because some of the chemicals used to manufacture the illicit drug are toxic to both mother and infant, specifically lead, which is quite harmful to the infant. Any drug use during lactation should be explored and the mother encouraged to discontinue breastfeeding if illicit drug use is a concern.
Alcohol and tobacco are two commonly used legal drugs that can affect the breastfed infant. Alcohol passes freely into breast milk and reaches levels close to maternal serum levels. High levels of alcohol in the breast milk put the infant at risk for sedation and cause a reduction in the maternal milk-ejecting response. There is controversy regarding maternal alcohol use during lactation. It is probably safe for the mother to ingest small amounts of alcohol timed just after a feeding, when levels in the milk are the lowest possible. Tobacco is a concern because of both secondhand smoke exposure and the nicotine that passes into breast milk. Nicotine passes freely into breast milk, and therefore the breastfed infant is exposed to this toxin. If a nicotine replacement patch is used for maternal smoking cessation, then the nicotine blood levels and therefore breast milk levels are lower than with smoked tobacco.
Because drugs are almost never tested for use in lactating women prior to their release onto the market, questions regard- ing their safety during breastfeeding always exist. Understanding some basic principles regarding the transfer of drugs into breast milk and their pharmacokinetic actions helps the practitioner make decisions about safe prescribing. The practitioner should have ready reference to the most current information available about drugs during lactation, including Drug Facts and Comparisons; Drugs in Pregnancy and Lactation by Biggs, Freeman, and Yaffe; and Teratogen Information Services, available from your local Poison Control Center.
The National Library of Medicine TOXNET (Toxicology Data Network) maintains a peer-reviewed, searchable online database of drugs in lactation: LactMed (http://toxnet.nlm.nih.gov/index.html).
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1327
Table 50–1 Effects of Commonly Prescribed Medications on Infants During Lactation
Drug Effect on Infant Comments
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1327
1328
Table 50–1 Effects of Commonly Prescribed Medications on Infants During Lactation—cont’d
Drug Effect on Infant Comments
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1328
Infants
1329
Table 50–1 Effects of Commonly Prescribed Medications on Infants During Lactation—cont’d
Drug Effect on Infant Comments
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School-Age Children
Adolescents
1330
CLINICAL PEARL
Infants • Parents are often unsure how to administer medica-
tion to an infant. While the parents are in the clinic with the child, the practitioner should address this issue and demonstrate how to do it. For ease of ad- ministration, use a medication syringe and insert the syringe into the mouth along the inner cheek. To de- crease choking, advise parents to squirt small amounts (1 mL) of medication at a time into the inner buccal space. Wait until the infant swallows, and then administer another small amount until all the medica- tion is administered. Direct parents not to administer the medication directly over the tongue, which in- creases choking and allows the infant more easily to spit out the medication.
• Advise parents to check with the pharmacist before mixing any medication with formula or breast milk; some medications are bound with the calcium or other ingredients in the formula, causing them to be less effective.
• Breastfed infants often choke and sputter when med- ications are first administered because these infants are used to only the feel of the breast in their mouths. Warning parents of this response and teaching them proper technique will help them gain confidence in medication administration.
• Giving acetaminophen in suppository form is an option if administering oral medications to the infant is difficult. The practitioner can demonstrate this procedure, which works well in breastfed infants especially.
Toddlers and Preschoolers
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FACTORS THAT INFLUENCE POSITIVE OUTCOMES
Specific Factors That Influence Compliance Long-Term Medication Regimens
Number of Medications Prescribed
Medication Interval
1331
CLINICAL PEARL
Electrolyte solutions • Pediatric electrolyte solutions are often not well ac-
cepted by children. One trick is to use electrolyte popsicles (Pedialyte) or freeze the bottled solution into homemade popsicles. The cold taste seems to be better accepted.
• Sugar-free Kool-Aid or another drink mix sweetened with Nutrasweet can be added to unflavored elec- trolyte solutions to make the taste of the electrolyte solution more acceptable to children.
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1331
Palatability
Cost
Family Issues
Improving Compliance in the Pediatric Patient
Medication Concentration
Written Versus Oral Instructions
Self-Monitoring Calendars
1332
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1332
Telephone/E-mail Reminders
Mobile Phone Medication Adherence Apps
Contracts and Reinforcement Programs
1333
Pain in children can range from teething pain to pain associated with otitis media. Parents often ask the practitioner about using acetaminophen or ibuprofen for the treatment of pain in children. For the safety of their children and the ef- ficacy of the medication, parents should be taught how to administer over-the-counter (OTC) pain medications properly.
The two most commonly used analgesics in pediatric patients are acetaminophen and ibuprofen. Aspirin should never be given to children for acute pain management due to the risk of Reye syndrome, and the practitioner should teach parents this rule.
Acetaminophen can be administered orally or rectally (suppository), and it peaks in 30–60 minutes. Dosage for children is 10–15 mg/kg/dose q4–6h.
Ibuprofen is effective for pain control and has an additive anti-inflammatory effect, which appears to provide better pain control in acute otitis media than acetaminophen. The correct dosage is 5–10 mg/kg/dose q6–8h. Ibuprofen should not be administered by parents to children under age 6 months because immature kidneys are unable to excrete it, leading to increased risk of toxicity and renal damage. All children receiving ibuprofen should be well hydrated to prevent renal damage. Avoid ibuprofen if fluid intake is decreased.
Although acetaminophen and ibuprofen provide good pain relief for mild to moderate pain and both have antipyretic effects, ibuprofen may be the drug of choice for night pain associated with otitis media because of its longer duration. Both drugs are equally easy to administer, although ibuprofen is not available in suppository form. Combining acetaminophen and ibuprofen in an alternating schedule for fever or pain is not recommended in the outpatient setting. One or the other, properly dosed, should be used. The goal of antipyretic therapy is not to reduce temperature to normal, but to decrease discomfort associated with fever.
Give parents a dosing chart with their child’s dose based on weight. The different strengths of acetaminophen must be dosed correctly.
BOX 50–2 PRESCRIBING OVER-THE-COUNTER PAIN MEDICATIONS FOR PEDIATRIC PATIENTS
CLINICAL PEARL
Improving compliance with ophthalmic preparations • Administration of ophthalmic preparations to tod-
dlers and preschoolers is often difficult, and the in- cidence of noncompliance increases with each dose that is a battle to administer. Parents can safely restrain the child to administer eye medications as follows: 1. Sit on the floor with the child sitting on the floor
between the parent’s legs. 2. Place the child’s feet near the parent’s feet and the
child’s head between the parent’s thighs. 3. Slip the child’s arms under the parent’s thighs and,
with the legs, hold the child’s head and arms still. The parent then has both hands free to administer
the eye medication. Although this procedure may sound drastic, it is a quick way for a parent to administer the medication when no other adult is around to assist with a squirming, resistant child. • Older preschoolers and school-age children often co-
operate with administration of eyedrops if they are told to lie back and close their eyes. Eyedrops can then be applied to the inner corner of the eyes (while the eyes are closed). Next, children are told to open their eyes, without any head movement. The medica- tion rolls into the eye when the eye is opened. This is much easier than the bull’s-eye approach of trying to get children to keep their eyes open for squeezing in drops.
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Childhood Obesity Influences Outcomes
REFERENCES
1334
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1334
1335
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1335
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1336
1337
CHAPTER 51
Joan M. Nelson
DEMOGRAPHICS, 1337 Diseases Associated With Aging
Pharmacological Issues in Aging
PHYSICAL CHANGES ASSOCIATED WITH AGING, 1338 Mental Changes
Sensory Changes
Musculoskeletal Changes
PHARMACOKINETIC CHANGES, 1339 Absorption and Distribution
Metabolism and Excretion
PHARMACODYNAMIC CHANGES, 1341
PHARMACOTHERAPEUTICS, 1341 Polypharmacy
Adverse Drug Reactions
Drug-Drug and Drug-Food Interactions
Alternative Medicines
Assessment
Adherence
Advice to Prescribers
Self-Medication Practices
Inappropriate Prescribing: Drugs to Be Avoided in Older Adults
TRANSITIONS OF CARE AND CARE SETTINGS, 1346
GENERAL PRINCIPLES FOR PRESCRIBING FOR OLDER ADULTS, 1348
P DEMOGRAPHICS
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Diseases Associated With Aging
Pharmacological Issues in Aging
PHYSICAL CHANGES ASSOCIATED WITH AGING
Mental Changes
Sensory Changes Sight
Hearing
1338
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1338
Smell and Taste
Peripheral Sensation
Musculoskeletal Changes
PHARMACOKINETIC CHANGES
Absorption and Distribution
Metabolism and Excretion
1339
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1339
1340
Table 51–1 Common Pharmacokinetic and Pharmacodynamic Changes in Older Adults
Pharmacokinetic Process Changes in Older Adults Implications
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1340
PHARMACODYNAMIC CHANGES
PHARMACOTHERAPEUTICS
Polypharmacy
1341
CLINICAL PEARL
Start low, go slow The Golden Rule of geriatrics: Start low, go slow, but go! Treat the problem, starting at lower dosages, and titrate up slowly over a longer period of time than for a younger person. Evaluate for ADRs before they become serious and costly.
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1341
Drug-Drug and Drug-Food Interactions
1342
CLINICAL PEARL
Avoiding ADRs The first step in avoiding ADRs is to establish risk pre- dictions. Polypharmacy is only part of the picture. Take into account age, gender, multiple comorbidities, body weight, renal and hepatic failure, and previous drug reactions. Avoid medications that create unnecessary risk for patients who are determined to be at high risk for ADR.
Adverse Drug Reactions
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Alternative Medicines
Assessment
1343
Table 51–2 Selected Common Drug-Drug Interactions in Older Adults
Drug Drug Interaction
CLINICAL PEARL
Medication review Have the older adult bring all the drugs he or she is taking, including herbs, vitamins, and OTC drugs, in a brown bag to the annual visit. This will enable you to see all the drugs and to determine if there are overlapping drugs that could be eliminated, combinations that could reduce the total number of drugs, or drugs prescribed by other providers that the patient failed to mention. It also helps to evaluate the patient’s knowledge of the drugs, including why the drug is being taken and if he or she understands the ADRs.
Using a thorough and quick checklist at each clinic visit with older adult patients provides an accurate eval- uation of their understanding of the drugs and their ability to manage the regimen. Box 51-1 is a questionnaire that may be used for this assessment.
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1343
1344
CLINICAL PEARL
Resources • A helpful resource to evaluate the quality and content
of herbs and supplements: National Center for Com- plementary and Integrative Health https://nccih.nih.gov/
• Helpful assessment tools: Try This and How to Try This Series—Resources for the care of older adults, including assessment tools and instructions for the proper use of those tools: http://consultgerirn.org/
• Did you bring all of your medications with you? • List your medications, and tell me how you
take them. • Do you have any new eye drops, either over the
counter or from your eye doctor? • What over-the-counter medications are you taking,
such as food supplements, vitamins, laxatives, pain relievers, and herbal or natural products?
• What medicine or herbs do you use for headaches, muscle aches or pains, nausea, or constipation?
• Do you have any problems opening the bottles? • Do you sometimes skip some of the medicine?
Why? • What do you do when you run out of your pills? • At what time of the day do you take your pills,
and do you do this the same every day? • How do you remember to take your pills? Do you
use a pill box? • How do you tell the difference between your
medications (size, color)? • What questions do you have about your
medications? • Do you have any difficulty paying for your
medications? • Who sets up and orders your medications?
BOX 51–1 QUESTIONNAIRE FOR ASSESSING MEDICATION MANAGEMENT
Adherence
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1344
Advice to Prescribers
Self-Medication Practices
Inappropriate Prescribing: Drugs to Be Avoided in Older Adults
1345
• Using another’s medications or remedies. • Changing the prescribed medication regimen
without informing the provider. • Utilizing self-care practices based on no or poor
information. • Neglecting to inform the health-care provider
about all therapies being utilized. • Hoarding medications.
BOX 51–2 POOR DRUG PRACTICES COMMONLY SEEN IN OLDER ADULTS
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1345
TRANSITIONS OF CARE AND CARE SETTINGS
1346
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1346
1347
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1347
GENERAL PRINCIPLES FOR PRESCRIBING FOR OLDER ADULTS
REFERENCES
1348
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1348
1349
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1349
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1350
1351
CHAPTER 52
Ruth L. Schaffler
OVERVIEW OF PAIN CONCEPTS, 1351 The Experience of Pain
Pain Threshold and Pain Tolerance
Neurological Basis of Pain
Special Populations
ACUTE PAIN, 1356 Pathophysiology
Signs and Symptoms
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
CHRONIC PAIN, 1364 Pathophysiology
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
OVERVIEW OF PAIN CONCEPTS
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The Experience of Pain
Pain Threshold and Pain Tolerance
1352
Table 52–1 Comparisons of Acute and Chronic Pain
Acute Chronic
Etiology
Onset
Localization
Duration
Character
Temporal pattern
Associated symptoms
Prognosis
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1352
Neurological Basis of Pain Anatomy and Physiology
1353
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1353
Pain Modulation
! " # ! "
! "
# ! #
$
Special Populations
1354
Cerebrum
Midbrain
Pons NE and 5-HT (efferent)
Medulla NE and 5-HT (efferent)
Spinal cord Receptor
Substance P Neurokinin A
Calcitonin gene–related peptide (afferent)
Somatic sensory area of cerebal cortex
Tertiary sensory neuron
Secondary sensory neuron
Collateral fibers to reticular formation
Lateral spinothalamic tractDorsal root
ganglion
Primary sensory neuron
Thalamus
Figure 52–1. Anatomy of pain transmission.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1354
Pediatric Patients
Older Adults
Cognitive Impairment
Comorbid Chronic Illnesses
Pregnancy
Substance Abuse
1355
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1355
ACUTE PAIN
Pathophysiology
Signs and Symptoms
1356
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1356
1357
Lung and diaphragm
Small intestine
Heart Liver Liver
Pancreas
Stomach
Ovary
Kidney
Colon
Bladder
Ureter Appendix
A B
Kidney
Figure 52–2. Referred pain sites.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1357
1358
C2 C3 C4
C5 T1
T2 T3
T4 T5
T6 T7
T8 T9
T10 T11 T12
T1 T2
T3 T4 T5 T6 T7 T8
T9 T10
T11 T12L1
L2 L3
L1 L2
L3
L4 L5
S1
L4
L5
S1
S2
S2 S3
S4
S5
C6
C5
C6
C6
C7
C7 C8
C8
C8 C7
C6 C5 C4 C3
C2
C8
T1
L4
L5
L5
L4
L3
S3
S2
L2
L1
S1
Levels of principal dermatomes
C5 C5, 6, 7 C8, T1 C6 C6, 7, 8 C8 T4
Clavicles Lateral parts of upper limbs Medial sides of upper limbs Thumb Hand Ring and little fingers Level of nipples
T10 T12 L1, 2, 3, 4 L4, 5, S1 L4 S1, S2, L5 S1 S2, 3, 4
Level of umbilicus Inguinal or groin regions Anterior and inner surfaces of lower limbs Foot Medial side of great toe Posterior and outer surfaces of lower limbs Lateral margin of foot and little toe Perineum
Figure 52–3. Spinal dermatomes.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1358
1359
Table 52–2 Behavioral Responses to Pain
Age Group Vocalizations Facial Expressions Body Movements Coping Strategies
Pharmacodynamics
Anti-Inflammatory Drugs
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1360
Table 52–3 Common Analgesics Used for Pain Relief
Classification Drug Indication Contraindications Side Effects Route
Nonopioids
Selected Analgesic Adjuncts
Opioids
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1360
1361
Opioids
! "
!
!
!
" ! "
Goals of Treatment
Addiction and Dependency
Table 52–3 Common Analgesics Used for Pain Relief—cont’d
Classification Drug Indication Contraindications Side Effects Route
Local Anesthetics/ Analgesics
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Rational Drug Selection
1362
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1362
1363
Patient assessment
Assess response to therapy.
If pain relief still ineffective or becomes chronic, move to Chronic Pain algorithm (Fig. 52–5).
Interventions to resolve cause of pain (e.g., rest, ice, compression, and elevation)
Analgesia
Adequate pain relief with tolerable side effects. Goal:
Return to normal ADLs Adequate pain relief
but intolerable side effects Inadequate pain relief or increased pain not
explained by initial cause
Adequate pain relief with tolerable side effects
Ineffective pain relief
Taper off drugs.
Continue to treat with drug and adjunct therapy
as needed.
Treat side effects. • Constipation is common. • Nausea may not be
related to drugs.
New pain cause
Return to interventions to resolve cause of pain.
Change medication May require opiates
Mild to moderate pain Salicylates
NSAIDs Acetaminophen
Severe pain Increased doses of drugs for mild to moderate pain
Use opiates.
Figure 52–4. Acute pain manage- ment algorithm.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1363
Monitoring
Outcome Evaluation
Patient Education
CHRONIC PAIN
1364
ACUTE PAIN MANAGEMENT PA TIENT
EDUCATI ON
Related to the Overall Treatment Plan and Disease Process
■■ Pathophysiology of pain and its cause (where appropriate), at a level the patient can understand, to explain how the drugs work.
■■ Importance of adherence to the treatment regimen.
■■ Indications for contacting the health-care provider when pain relief is ineffective.
■■ Need for follow-up visit(s) with the primary care provider.
Specific to the Drug Therapy
■■ Reasons for taking the drug(s) and the anticipated action of these drug(s) in pain relief.
■■ Doses and schedules for taking the drug(s), including early round-the-clock dosing of drugs.
■■ Possible adverse reactions and what to do if they occur.
Reasons for Taking the Drug(s)
■■ Patient education about specific drugs is provided in Chapters 15 and 25. The explanations should be clear about what pain drugs can and cannot do.
Drugs as Part of the Total Treatment Regimen
■■ Role of both pharmacological and nonpharmacological treatments for pain and their interconnection.
Adherence Issues
■■ The fact that most acute pain can be resolved should be stressed. The importance of that resolution to avoid the development of chronic pain should be addressed.
■■ Adherence to the drug regimen is important to resolving acute pain.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1364
Pathophysiology
Nociceptive Pain
Neurogenic Pain
Psychogenic Pain
Pharmacodynamics
1365
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1365
Goals of Treatment
Rational Drug Selection
Lifestyle Modifications
Cognitive-Behavioral Interventions
Drug Therapy
Anti-Inflammatories
1366
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1366
1367
In fre
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To pi
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3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1367
Adjuvant Analgesics
!
Opioids
1368
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1368
Outcome Evaluation
Patient Education
1369
Monitoring
RECLASSIFICATION OF HYDROCODONE AS SCHEDULE II In 2013 the U.S. Food and Drug Administration (FDA) recommended that the U.S. Drug Enforcement Adminis- tration (DEA) reclassify hydrocodone from a Schedule III to a Schedule II drug due to the misuse and abuse of the drug. In October 2014 the DEA reclassified hy- drocodone, the most prescribed opioid in the United States, as a Schedule II drug.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1369
REFERENCES
1370
CHRONIC PAIN MANAGEMENT
Related to the Overall Treatment Plan and Disease Process
■■ Pathophysiology of pain and its cause (where appropriate), at a level the patient can understand, to explain how the drugs work.
■■ Role of lifestyle modification in improving prognosis and keeping the number and cost of required drugs and other treatments down.
■■ Indications for contacting the health-care provider when pain relief is ineffective.
■■ Need for follow-up visit(s) with the primary care provider.
Specific to the Drug Therapy
■■ Reasons for taking the drug(s) and the anticipated action of these drug(s) in pain relief.
■■ Doses and schedules for taking the drug(s), including round-the-clock dosing of drugs.
■■ Possible adverse reactions and what to do if they occur.
■■ Coping mechanisms to deal with the complex and costly treatment regimens.
Reasons for Taking the Drug(s)
■■ Patient education about specific drugs is provided in Chapters 15 and 25. The explanations should be clear about what pain drugs can and cannot do.
■■ Patient should be made aware that the drug(s) may need to be taken over a long period of time, so interventions to reduce adverse reactions and reporting them when they occur are important.
Drugs as Part of the Total Treatment Regimen
■■ Role of both pharmacological and nonpharmacological treatments for pain and their interconnection.
Adherence Issues
■■ The fact that most chronic pain cannot be resolved should be addressed.
■■ Adherence to the drug regimen is important to improving chronic pain.
■■ Adherence to lifestyle issues is equally important.
■■ Discussion of ways to remove barriers to adherence should occur.
PATIENT EDUCATI
ON
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1371
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1371
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1372
A
1373
Index
3827_Index_1373-1398 10/07/15 10:10 AM Page 1373
1374
3827_Index_1373-1398 10/07/15 10:10 AM Page 1374
1375
3827_Index_1373-1398 10/07/15 10:10 AM Page 1375
B
1376
3827_Index_1373-1398 10/07/15 10:10 AM Page 1376
1377
C
3827_Index_1373-1398 10/07/15 10:10 AM Page 1377
1378
3827_Index_1373-1398 10/07/15 10:10 AM Page 1378
1379
D
3827_Index_1373-1398 10/07/15 10:10 AM Page 1379
1380
3827_Index_1373-1398 10/07/15 10:10 AM Page 1380
1381
E
3827_Index_1373-1398 10/07/15 10:10 AM Page 1381
F
1382
3827_Index_1373-1398 10/07/15 10:10 AM Page 1382
1383
G
3827_Index_1373-1398 10/07/15 10:10 AM Page 1383
H
1384
3827_Index_1373-1398 10/07/15 10:10 AM Page 1384
1385
3827_Index_1373-1398 10/07/15 10:10 AM Page 1385
I
1386
3827_Index_1373-1398 10/07/15 10:10 AM Page 1386
1387
J
K
L
3827_Index_1373-1398 10/07/15 10:10 AM Page 1387
M
1388
3827_Index_1373-1398 10/07/15 10:10 AM Page 1388
1389
N
3827_Index_1373-1398 10/07/15 10:10 AM Page 1389
O
1390
3827_Index_1373-1398 10/07/15 10:10 AM Page 1390
1391
P
3827_Index_1373-1398 10/07/15 10:10 AM Page 1391
1392
3827_Index_1373-1398 10/07/15 10:10 AM Page 1392
1393
Q
R
3827_Index_1373-1398 10/07/15 10:10 AM Page 1393
S
1394
3827_Index_1373-1398 10/07/15 10:10 AM Page 1394
1395
T
3827_Index_1373-1398 10/07/15 10:10 AM Page 1395
1396
3827_Index_1373-1398 10/07/15 10:10 AM Page 1396
1397
U
V
3827_Index_1373-1398 10/07/15 10:10 AM Page 1397
W
X
Y
Z
1398
3827_Index_1373-1398 10/07/15 10:10 AM Page 1398
- Cover
- Title Page
- Copyright
- Dedication
- PREFACE
- ABOUT THE AUTHORS
- CONTRIBUTORS
- REVIEWERS
- CONTENTS
- UNIT I
- Chapter 1 THE ROLE OF THE ADVANCED PRACTICE NURSE AS PRESCRIBER
- Chapter 2 REVIEW OF BASIC PRINCIPLES OF PHARMACOLOGY
- Chapter 3 RATIONAL DRUG SELECTION
- Chapter 4 LEGAL AND PROFESSIONAL ISSUES IN PRESCRIBING
- Chapter 5 ADVERSE DRUG REACTIONS
- Chapter 6 FACTORS THAT FOSTER POSITIVE OUTCOMES
- Chapter 7 CULTURAL AND ETHNIC INFLUENCES IN PHARMACOTHERAPEUTICS
- Chapter 8 AN INTRODUCTION TO PHARMACOGENOMICS
- Chapter 9 NUTRITION AND NUTRACEUTICALS
- Chapter 10 HERBAL THERAPY AND NUTRITIONAL SUPPLEMENTS
- Chapter 11 INFORMATION TECHNOLOGY AND PHARMACOTHERAPEUTICS
- Chapter 12 PHARMACOECONOMICS
- Chapter 13 OVER-THE-COUNTER MEDICATIONS
- UNIT II PHARMACOTHERAPEUTICS WITH SINGLE DRUGS
- Chapter 14 DRUGS AFFECTING THE AUTONOMIC NERVOUS SYSTEM
- Chapter 15 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM
- Chapter 16 DRUGS AFFECTING THE CARDIOVASCULAR AND RENAL SYSTEMS
- Chapter 17 DRUGS AFFECTING THE RESPIRATORY SYSTEM
- Chapter 18 DRUGS AFFECTING THE HEMATOPOIETIC SYSTEM
- Chapter 19 DRUGS AFFECTING THE IMMUNE SYSTEM
- Chapter 20 DRUGS AFFECTING THE GASTROINTESTINAL SYSTEM
- Chapter 21 DRUGS AFFECTING THE ENDOCRINE SYSTEM
- Chapter 22 DRUGS AFFECTING THE REPRODUCTIVE SYSTEM
- Chapter 23 DRUGS AFFECTING THE INTEGUMENTARY SYSTEM
- Chapter 24 DRUGS USED IN TREATING INFECTIOUS DISEASES
- Chapter 25 DRUGS USED IN TREATING INFLAMMATORY PROCESSES
- Chapter 26 DRUGS USED IN TREATING EYE AND EAR DISORDERS
- UNIT III PHARMACOTHERAPEUTICS WITH MULTIPLE DRUGS
- Chapter 27 ANEMIA
- Chapter 28 CHRONIC STABLE ANGINA AND LOW-RISK UNSTABLE ANGINA
- Chapter 29 ANXIETY AND DEPRESSION
- Chapter 30 ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE
- Chapter 31 CONTRACEPTION
- Chapter 32 DERMATOLOGICAL CONDITIONS
- Chapter 33 DIABETES MELLITUS
- Chapter 34 GASTROESOPHAGEAL REFLUX AND PEPTIC ULCER DISEASE
- Chapter 35 HEADACHES
- Chapter 36 HEART FAILURE
- Chapter 37 HUMAN IMMUNODEFICIENCY VIRUS DISEASE AND ACQUIRED IMMUNODEFICIENCY SYNDROME
- Chapter 38 HORMONE REPLACEMENT THERAPY AND OSTEOPOROSIS
- Chapter 39 HYPERLIPIDEMIA
- Chapter 40 HYPERTENSION
- Chapter 41 HYPERTHYROIDISM AND HYPOTHYROIDISM
- Chapter 42 PNEUMONIA
- Chapter 43 SMOKING CESSATION
- Chapter 44 SEXUALLY TRANSMITTED INFECTIONS AND VAGINITIS
- Chapter 45 TUBERCULOSIS
- Chapter 46 UPPER RESPIRATORY INFECTIONS, OTITIS MEDIA, AND OTITIS EXTERNA
- Chapter 47 URINARY TRACT INFECTIONS
- UNIT IV SPECIAL DRUG TREATMENT CONSIDERATIONS
- Chapter 48 WOMEN AS PATIENTS
- Chapter 49 MEN AS PATIENTS
- Chapter 50 PEDIATRIC PATIENTS
- Chapter 51 GERIATRIC PATIENTS
- Chapter 52 PAIN MANAGEMENT: ACUTE AND CHRONIC PAIN
- Index
