Pharmacology Renal/Genitourinary agents.

sankarolina9

Renal1.ppt

Home >Nursing homework help >Pharmacology Renal/Genitourinary agents.

CHAPTER 32

Diuretics

DRUG OVERVIEW

Diuretics

Thiazides and thiazide-like inhibitors

Sodium channel blockers

Loop Diuretics

Carbonic anhydrase inhibitors

Potassium-sparing

Sodium channel blockers

Aldosterone antagonists

Fixed-dose combination therapies

HCTZ with amiloride, spironolactone, or triamterene

Potassium supplements

Facilitate Loss of sodium and water

Reduce Cardiac Output and blood pressure

After usually 8 weeks return to normal (CO)

BP remains reduced

INDICATIONS

Hypertension
Congestive heart failure
Renal failure
Cirrhosis

THIAZIDE DIURETICS: MECHANISM OF ACTION

5%-7% of filtered Na is reabsorbed

Inhibit sodium reabsorption in the distal tubule through inhibition of NaCl transporter

Effect blunted by reabsorption of sodium distally in cortical collecting tubule

Less efficacious for edema

During long-term therapy for HTN, may decrease peripheral vascular resistance

Enhance calcium absorption and lessen excretion

Used as initial therapy, either alone or in combo with ACE inhibitors ARB B blockers or Calcium channel blocers

MOA: Inhibit sodium reabsorption in the distal tubules causing increased excretion of sodium and water, potassium and hydrogen ions

Adverse effects: Potassium depletion, mag, hyponatremia, hyperglycemia, increase serum lipid concentrations, precipitate gout

LOOP DIURETICS: MECHANISM OF ACTION

20% of filtered Na is reabsorbed

Inhibit reabsorption of sodium and chloride in ascending loop of Henle and distal renal tubule and cause increased excretion of water, sodium, chloride, magnesium and calcium

Promote excretion of calcium: Clinically relevant effect

Adverse effects: Hypokalemia, hyperuricemia, gout, metabolic alkalosis, hypomagnesemia, hyponatremia, hyperglycemia

CARBONIC ANHYDRASE INHIBITORS:
MECHANISM OF ACTION

50%-75% of filtered Na is reabsorbed

Diuretic response is weak

Most filtered sodium is reclaimed by loop of Henle and distal nephron

Inhibition causes luminal hydrogen ion concentrations to rise, and activity of Na/H exchanger is inhibited

Loss of bicarbonate in urine

Treatment of metabolic alkalosis

Leads to severe metabolic acidosis

POTASSIUM-SPARING DIURETICS
MECHANISM OF ACTION

Sodium channel blockers

Block sodium reabsorption → slowing potassium excretion → leading to potassium retention

Net diuretic effect: 1%-2% of filtered sodium

Commonly paired with loop or thiazide diuretic

Refractory edema

Prevention of excess potassium loss

Mechanism of Action:

Interfere with potassium/sodium exchange in the distal tubule, cortical collecting tubule and collecting duct by inhibiting sodium, potassium,-ATPase; decreases calcium excretion, increases magnesium loss

Adverse effects: Hyperkalemia, hyponatremia, gynecomastia, hyperchloremic metabolic acidosis

POTASSIUM-SPARING DIURETICS: MECHANISM OF ACTION

Aldosterone antagonists (spironolactone and eplerenone)

Competitively inhibit aldosterone receptors, preventing activation of inactive luminal sodium channels and stimulation of production of additional sodium channels

Net diuretic effect: 1%-2% of filtered sodium

Treatment of cirrhosis and ascites

Improve survival in patients with heart failure

Eplerenone: More specific inhibitor of aldosterone; fewer side effects than spironolactone

TREATMENT PRINCIPLES

Salt restriction

Thiazide: First line

Loop: Second line

Other diuretics as needed for specific conditions

TREATMENT PRINCIPLES (CONT.)

Patients are less responsive to diuretics as renal function declines

Efficacy of loop diuretics is maintained in moderately severe renal insufficiency, but increased dosage is necessary

Thiazides are relatively ineffective with a GFR 30-40 mL/min

Exceptions: Metolazone and indapamide

Potassium-sparing drugs should be used with caution or avoided in patients with renal insufficiency

TREATMENT PRINCIPLES (CONT.)

Length of time on therapy may contribute to responsiveness

Ability of diuretic to increase renal NaCl excretion declines over time

Diuretic resistance: 1:3 patients with HF

Second drug may mitigate this process

Evaluate patient noncompliance with medication regimen or low-sodium diet

Evaluate for HF, renal failure, nephrotic syndrome, and cirrhosis

Evaluate for drug interactions that cause resistance

(See Boxes 32-1 and 32-2)

TREATMENT PRINCIPLES (CONT.)

Thiazides

Most frequently used and least expensive

Initial treatment of HTN

Addition of a thiazide to a loop diuretic + Na restriction with refractory edema may be useful

 New stone formation with idiopathic hypercalciuria

 Urine volume with nephrogenic diabetes insipidus

Major complications: Electrolyte imbalance

TREATMENT PRINCIPLES (CONT.)

Thiazides

Start at lowest dose

Doses no greater than 25 mg daily of HCTZ or chlorthalidone should be used for treatment of HTN

TREATMENT PRINCIPLES (CONT.)

Loop diuretics

Treat volume excess

CHF, nephrotic syndrome, acute and chronic renal insufficiency, cirrhosis

Dose equivalencies

Furosemide 40 mg = bumetanide 1 mg

Furosemide 40 mg = torsemide 20 mg

Diuresis in patients with normal renal function

10-40 mg furosemide

Maximal equivalent doses of bumetanide and torsemide are 1 mg and 20 mg, respectively

TREATMENT PRINCIPLES (CONT.)

Loop diuretics

Treatment of congestive symptoms of pulmonary and peripheral edema

Symptom relief with loop: Hours to days

Symptom relief with ACEI and digoxin: Weeks to months to reach maximal effects

Starting dose: 20-40 mg furosemide daily

Dosing guided by diuretic response; increase every 1-2 weeks

Monitor with daily weight log

TREATMENT PRINCIPLES (CONT.)

Loop diuretics

Toxicities

Fluid and electrolyte imbalance

Hypersensitivity reaction:

Sulfonamide derivatives

Ototoxicity

Fluid and electrolyte imbalance

Hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, hyperuricemia

Metabolic alkalosis

Elevations in BUN and serum creatinine

Hypersensitivity reaction: Sulfonamide derivatives

Careful with “sulfa allergies”

Nonsulfonamide loop diuretic ethacrynic acid is reserved for those who have a true allergic reaction to a loop or thiazide diuretic

Ototoxicity

May be permanent

Reported in treatment of acute renal failure at doses 80 to 160 mg per hour

Concurrent use of aminoglycosides may enhance this process at lower doses of the diuretic

TREATMENT PRINCIPLES (CONT.)

Carbonic anhydrase inhibitors

Weak diuretics

Treatment of open-angle glaucoma

Prophylaxis and treatment of acute mountain sickness

Acetazolamide

May be used in combination with other diuretics to treat HF

Used to treat metabolic alkalosis

TREATMENT PRINCIPLES (CONT.)

Potassium-sparing diuretics

Used in combination with thiazides to augment diuresis and blunt hypokalemic effects of thiazides and loops

Spironolactone

Treatment of HF (RALES trial)

Eplerenone

Designed to minimize endocrine side effects of spironolactone

Treatment of HF (EPHESUS trial)

TREATMENT PRINCIPLES (CONT.)

Osmotic diuretics

Mannitol:

Inhibits sodium reabsorption in the proximal tubule and loop of Henle

Use limited to inpatient settings to  ICP or to  intraocular pressure in glaucoma

Combination diuretics

Thiazide and potassium-sparing combinations

Loop and thiazide combinations

Loop and carbonic anhydrase inhibitors

PATIENT VARIABLES

Geriatrics

Age-related decline in renal function

Diuretic-induced electrolyte imbalances

Decreased GFR diminishes diuretic response

(especially thiazides)

Indicated for treatment of isolated systolic hypertension at low doses (SHEP trial)

PATIENT VARIABLES (CONT.)

Pediatrics

Safety and efficacy have been established

Potential glucose elevation and lipid and electrolyte abnormalities

May be used for patients with edema, glaucoma, and epilepsy

Careful monitoring

Changes in personality or sleeping patterns

Restlessness

PATIENT VARIABLES (CONT.)

Pregnancy and lactation

Category C

Race and gender

Gender has not been identified as a consideration in diuretic therapy

African Americans respond better to diuretics than to other antihypertensive medications

CHAPTER 33

Male Genitourinary Agents

DRUG OVERVIEW

Benign prostatic hyperplasia (BPH)

α1-Adrenergic antagonist

α1A-Selective: Tamsulosin (Flomax)

Long-acting α1: Doxazosin (Cardura)

Short-acting α1: Prazosin (Minipress)

5α-Reductase inhibitors

Finasteride (Proscar)

Dutasteride (Avodart)

Erectile dysfunction (ED)

PDE5 inhibitor

Sildenafil (Viagra)

Tadalafil (Cialis)

Vardenafil (Levitra)

Other

Alprostadil (Caverject)

Yohimbine (Yocon)

BENIGN PROSTATIC HYPERPLASIA

Mechanism of action

α1-Adrenergic receptor blockers

 Sympathetic tone

Relax urethral stricture

5α-Reductase inhibitors

 Size of prostate

6-12 months for effect

BENIGN PROSTATIC HYPERPLASIA (CONT.)

Surgery is primary treatment for BPH

Treatment is initiated when symptoms become problematic

All α-blockers are considered equally efficacious

α-Blockers are best for quick symptom relief

5α-Reductase inhibitors can prevent growth of the prostate over the long-term:

Finasteride

Goals:

Alleviate symptoms

Maintain kidney function

BENIGN PROSTATIC HYPERPLASIA (CONT.)

Category X: Finasteride, dutasteride

FDA has issued a warning of an increased risk of high-grade prostate cancer while taking 5α-reductase inhibitors

Combination therapy with finasteride and doxazosin shown to lower the risk of clinical progression of BPH by 66%

Herbal treatment with saw palmetto is popular

It acts as a 5α-reductase inhibitor

Finasteride/dutasteride is teratogenic. Finasteride tablets must not be touched by a woman who may be pregnant because the product may be absorbed through the skin. A pregnant woman should not come in contact with the semen of a man who is taking finasteride.

Finasteride: Anabolic hormone inhibitors, block dihydrotestosterone production, reduce prostate tissue growth, reducing symptoms

Long latency period before effect

Useful only for men with large prostate-meta-analysis

Sexual side effects: Libido

MECHANISM OF ACTION: DRUGS FOR ED

PDE5 inhibitors

Enzyme

Maintain smooth muscle relaxation and promote inflow of blood flow

Alprostadil (Caverject)

Prostaglandin

Corporeal venoocclusive mechanism

Yohimbine (Yocon)

Alkaloid

Stimulates presynaptic norepinephrine release in lower nerve centers

PDE5 Inhibitors: A phosphodiesterase type 5 inhibitor is a drug used to block the degradative action of cGMP-specific phosphodiesterase type 5 on cyclic GMP in the smooth muscle cells lining the blood vessels supplying the corpus cavernosum of the penis

TREATMENT PRINCIPLES: ED

Pharmacologic treatment

Hormone replacement

PDE5 inhibitors

Intraurethral prostaglandin

Yohimbine

Nonpharmacologic treatment

Vascular reconstruction

Vacuum constriction devices

Implanted penile prostheses

CHAPTER 34

Agents for Urinary Incontinence and Urinary Analgesia

INDICATIONS

Drug specific

Dysuria

Neurogenic bladder

Overactive bladder

Urge incontinence, frequency, urgency

Adjunctive therapy of peptic ulcer

Primary nocturnal enuresis (intranasal)

Urinary retention

MECHANISM OF ACTION

Anticholinergics

Blockade of muscarinic actions

Inhibit the action of acetylcholine on bladder smooth muscle

Cholinergic agonists

Stimulation of parasympathetic system

Release of acetylcholine, increasing detrusor muscle tone

MECHANISM OF ACTION (CONT.)

Desmopressin

Strong antidiuretic; decreases urine output for ~6 hours

Urinary tract analgesia: Phenazopyridine

An azo dye that is excreted in the urine; exerts a topical analgesic effect on urinary tract mucosa

TREATMENT PRINCIPLES

Stress incontinence

Beneficial: SSRIs (duloxetine), estrogen cream, ring, imipramine, pseudoephedrine

Likely to be beneficial: Pelvic floor electrical stimulation, pelvic floor muscle exercises, vaginal cones

Tradeoff between benefits and harms: Estrogen supplements

Urge incontinence

First line: Oxybutynin, darifenacin, solifenacin, tolterodine, trospium

Second line: TCAs

Third line: Flavoxate, propantheline, dicyclomine

TREATMENT PRINCIPLES (CONT.)

Nonpharmacologic treatment

Mainstay of treatment

Fluid management

Bladder training

Bladder retraining

Pelvic floor muscle rehabilitation