Discussion 2

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Chapter 5 The Actions of Drugs

Sources of Drugs

Many drugs are chemically derived from plants

Why do plants produce so many psychoactive drugs?

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Names of Drugs

Chemical name

Gives a complete chemical description of the molecule

derived from the rules of organic chemistry for naming any compound

Generic name

Official or legal name of drugs

listed in the United States Pharmacopoeia or U S P

Example: amphetamine

cannot be trademarked

Brand name

Specific drug or formulation trademarked by manufacturers

Patented drugs can be manufactured and sold for 20 years without direct competition by the companies that discovered and patented them

Example: Vyvanse, or lisdexamfetamine dimesylate

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Categories of Drugs, 1

Stimulants produce wakefulness and a sense of energy and well-being

Depressants slow nervous system activity

Opioids or narcotics produce a relaxed, dreamlike state

Hallucinogens produce altered perceptions

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Categories of Drugs, 2

Psychotherapeutic drugs are prescribed by physicians for the control of mental disorders

Some drugs belong to multiple categories

Examples: Marijuana and nicotine

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Figure 5.1: Classification of Psychoactive Drugs

Jump to Figure 5.1: Classification of Psychoactive Drugs, Appendix

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Figure 5.1 from text

Drug Identification

Physicians can tell from appearance of the drug the exact drug and dose

The Physician’s Desk Reference or P D R includes photographs of legally manufactured pharmaceuticals

Illegal drugs are sometimes marked, packaged, or labeled in an identifiable way

Example: M D M A

Drugs can also be tested and identified through chemical analyses

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Types of Drug Effects

Nonspecific effects

derive from the user’s unique background and particular perceptions of the environment

Also called placebo effects, because they can be produced by an inactive chemical that the user believes to be a drug

Important in treating pain and depression

Specific effects

depend on the presence of a chemical at certain concentrations in the target tissue

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Double-Blind Procedure

Tests for the effectiveness of a new drug

Neither the experimental participants nor the researchers know whether a subject is receiving a placebo or an experimental drug

The blinding code is “broken” after the drug trial is over

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Dose-Response Relationships

Dose-response curve

Graph depicting the relationship between a range of drug doses and the resulting drug effects

Threshold

the lowest dose at which an effect is observed

Different dose-response curves can be created for different drug effects

Some response systems have higher thresholds

Some drugs have an all-or-none dose-response relationship

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Figure 5.2: Relationship between Alcohol Dose and Multiple Responses

Jump to Figure 5.2: Relationship between Alcohol Dose and Multiple Responses, Appendix

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Estimating the Safety Margin, 1

Safety margin

Difference between the dose that produces the desired therapeutic effect in most patients and the lowest dose that produces an unacceptable toxic reaction

Potency

Amount of a drug required to produce a particular effect

Side effects

Unintended effects that accompany therapeutic effects

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Estimating the Safety Margin, 2

Effective dose

dose of a drug that produces a meaningful effect in some percentage of test subjects

E D50 is the effective dose for half the animals in a drug test

Lethal dose

dose of a drug that has a lethal effect in some percentage of test subjects

L D50 is the lethal dose for half of the animals in a drug test

Therapeutic index

Defined as L D50 divided by E D50

Should always be greater than one

Most drugs have an L D1 well above the E D95 level

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Time-Dependent Factors

The time course of a drug’s effect depends on:

how the drug is administered

how rapidly the drug is absorbed

Lipid solubility affects the extent to which a psychoactive drug dissolves in oils and fats

how the drug is eliminated from the body

Drug effects can be prolonged by taking additional doses at specific time intervals

Intervals vary from one drug to another

Taking multiple doses too close together will increase the maximum blood level with each dose, which can result in cumulative effects

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Figure 5.3: Possible Relationship between Drug Concentration in the Body and Measured Effect of the Drug

Jump to Figure 5.3: Possible Relationship between Drug Concentration in the Body and Measured Effect of the Drug, Appendix

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Routes of Administration

Oral administration

Insufflation

Intravenous injection

Subcutaneous and intramuscular injection

Inhalation

Jump to Route of Administration, Appendix

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Oral Administration

Absorption from the gastrointestinal tract is the most complicated way to enter the bloodstream

Drugs must withstand digestive processes and not be deactivated by food before they are absorbed

Drugs must then pass through the cells lining the gastrointestinal tract and into the blood capillaries

Only lipid-soluble and very small water-soluble molecules are readily absorbed into the capillaries

Drugs then pass through the liver

Very little may get into circulation if they get metabolized rapidly

©Corbis/VCG/Getty Images RF

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Image source: ©Corbis/VCG/Getty Images RF

Insufflation

Onset of effects is faster than it is for oral administration

Absorption through mucous membranes into the bloodstream occurs rapidly, bypassing the liver

Drawback associated with intranasal drug use includes nasal necrosis, or death of cells in the septal region

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Intravenous Injection

Drug is delivered directly into the bloodstream

Results in a rapid onset of its effects than does with oral administration or with other means of injection

Irritating material may be injected this way, because blood vessel walls are relatively insensitive

High concentrations can be delivered

Risks

Veins may become damaged over time

Blood-borne diseases spread easily

©Ingram Publishing/Ingram Publishing/Getty

Images RF

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Image source: ©Ingram Publishing/Ingram Publishing/Getty Images RF

Subcutaneous and Intramuscular injections

Subcutaneous injection

Injection under the skin

Also known as “skin popping”

If the material injected is extremely irritating to the tissue, the skin around the site of injection might die and be shed

Intramuscular injection

Absorption is more rapid from intramuscular injection than from subcutaneous injection because of the greater blood supply in muscles

Absorption of drugs is most rapid when the injection is into the deltoid muscle of the arm and least rapid when the injection is in the buttock

Larger volumes of material can be deposited in a muscle

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Inhalation

Efficient way of delivering a drug

Onset of drug effects is rapid because the capillary walls are accessible in the lungs, and the drug thus enters the blood quickly

Produces more rapid effects for psychoactive drugs than intravenous administration

Blood from the lungs, which contains the drug, moves directly to the brain

©Igor Stevanovic/123RF RF

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Image Source: ©Igor Stevanovic/123RF RF

Table 5.1: Some Characteristics of Routes of Drug Administration, 1

Route	Advantages	Disadvantages
Oral	Usually more safe Convenient	Absorption rate can be unpredictable Slow onset of drug effects
Insufflation	Liver metabolism avoided Rapid drug effects Reliable and convenient	Potential for nasal necrosis
Intravenous injection	Liver metabolism avoided Rapid drug effects	Suitable for irritating substances Increased risk of adverse effects Example for direct effects: overdose Example for indirect effects: potential for blood-borne diseases Potential for collapsed veins

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Table 5.1: Some Characteristics of Routes of Drug Administration, 2

Route	Advantages	Disadvantages
Subcutaneous injection	Drug absorption can be slow and constant providing a sustained drug effect	Potential for pain and necrosis from irritating substances
Intramuscular injection	Drug effects are more rapid than subcutaneous route	Suitable for irritating substances Drug absorption can be unpredictable or unusual in very obese and emaciated individuals
Smoked	Liver metabolism avoided Rapid drug effects	Increased risk of direct adverse effects Potential for lung toxicity

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Transport in the Blood, 1

Drug molecules attach to protein molecules

Most common protein involved: albumin

Inactive in this state and cannot leave the blood

Protected from inactivation by enzymes

Free or unbound drug molecules can move to sites of action in the body

Release of protein-bound drug occurs to maintain the proportion of bound to free molecules

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Transport in the Blood, 2

Drugs vary in their affinity for binding with plasma proteins

A drug with high affinity will displace a drug with low affinity, and thus, the drug with low affinity exists in the unbound form

Increase in the unbound drug concentration helps move the drug out of the bloodstream to the sites of action faster

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Blood-Brain Barrier

In general, only small lipophilic molecules enter the brain

Heroin is more lipophilic than morphine, and thus, it is more potent

About 85 percent of brain capillaries are covered with glial cells, and there is little extracellular space next to the blood vessel walls

Active transport systems may be needed to move chemicals in and out of the brain

Cerebral trauma can impair the blood-brain barrier and permit agents to enter that normally would be excluded

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Mechanisms of Drug Action

Effects on all neurons

Drugs act on the semipermeable membrane of neurons

Alter the electrical characteristics of the neuron by influencing its permeability

Effects on specific neurotransmitter systems

Drugs may alter the availability of a neurotransmitter by changing the transmitter chemical’s rate of:

Synthesis

Metabolism

Release from storage vesicles

Reuptake into the releasing neuron

Drugs may activate or prevent the activation of a receptor

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Drug Interactions

All depressant drugs, alcohol, and all narcotics tend to slow down the respiration rate

Combining any of these drugs can result in respiratory depression

Combining stimulants and depressants

Complicated interactions occur

Example: Combination of an upper, or methamphetamine, and a downer, or alcohol

Methamphetamine lessens alcohol-related performance disruptions

Alcohol lessens methamphetamine-related sleep disruptions

Produces greater increases in heart rate and euphoria

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Drug Deactivation, 1

A drug ceases to have an effect when it is excreted unchanged from the body or is chemically changed

Common way is for enzymes in the liver to act on the drug molecules to change their chemical structure

Enzyme Induction

When the body’s cells detect the presence of a foreign drug, they produce more of the enzyme that breaks down that molecule

C Y P 450 family, the most important drug-metabolizing liver enzymes, is specialized to inactivate various general foreign chemicals ingested

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Drug Deactivation, 2

Important for:

Tolerance to a particular drug

Interactions with other drugs broken down by the same enzyme

Increased rate of metabolism may alter the effectiveness of a previously effective drug dose

Many drugs have active metabolites that produce effects similar to those of the original drug and prolong the effects considerably

Example: marijuana and diazepam, or valium

Prodrugs are being developed

Inactive in original form and active only when altered by liver enzymes

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Tolerance and Withdrawal Symptoms

Drug disposition, or pharmacokinetic, tolerance

Increased metabolism or excretion reduces the effect of the subsequent dose

May relate to enzyme activity or the alteration of the p H of the urine

Behavioral tolerance

Drug continues to have the same biochemical effect but with a reduced effect on behavior

Reduced behavioral effect is a result of a drug user learning to compensate

Pharmacodynamic tolerance

leads to a reduced effectiveness of the drug

Causes withdrawal symptoms

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appendices

Figure 5.1: Classification of Psychoactive Drugs, Appendix

The figure shows the head of a man facing sideways, and the area of his brain is labeled psychoactive drugs. There are seven boxes extending from the center that list the various types of drugs with examples. The boxes are labeled stimulants, hallucinogens, cannabinoids, depressants, opioids, psychotherapeutics, and nicotine. Examples given for stimulants are cocaine, amphetamine, and caffeine. Examples given for hallucinogens are psilocybin, L S D, and ayahuasca. Examples given for cannabinoids are Cannabis; delta-9-tetrahydrocannabinol, or T H C; cannabidiol, or C B D; and nabilone. Examples given for depressants are alcohol, benzodiazepines, other sedatives, sleeping pills, and inhalants. Examples given for opioids are morphine, codeine, heroin, and oxycodone. Examples given for psychotherapeutics are cymbalta and abilify.

Jump back to Figure 5.1: Classification of Psychoactive Drugs

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Figure 5.2: Relationship between Alcohol Dose and Multiple Responses, Appendix

The x-axis of the graph represents the dose of alcohol, and the y-axis represents the percentage of individuals showing the effect. The x-axis ranges from low to high. The y-axis ranges from 0 to 100 at intervals of 10. There are three S-shaped curves slightly sloped to the right. These are labeled slowed reaction time, ataxia, and coma. All three curves begin at a point slightly above 0 on the y-axis and end at approximately 90 on the y-axis. The curve for slowed reaction time lies in the left region on the x-axis, which is labeled low; the curve for ataxia lies in the central region of the x-axis; and the curve for coma lies in the right region on the x-axis, which is labeled high.

Jump back to Figure 5.2: Relationship between Alcohol Dose and Multiple Responses

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Figure 5.3: Possible Relationship between Drug Concentration in the Body and Measured Effect of the Drug, Appendix

The graph consists of a horizontal axis labeled time. The left end of the horizontal axis is labeled point of drug administration. There are two curves, one below the other, and begin at the point of drug administration. The curve on the top is bell shaped curve and represents the concentration of drug in the blood. It has labels from A to G at equal intervals throughout the curve. The curve below it represents the measured effect of drug. It is constant in the beginning until the point B, after which there is a steep increase until the point C. It assumes a constant path until the point E, followed by a steep decrease until the point F. It then remains constant until G.

Jump back to Figure 5.3: Possible Relationship between Drug Concentration in the Body and Measured Effect of the Drug

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Routes of Administration, Appendix

During intravenous injection, drugs move into the lungs through the right side of the heart and move out through the left side of the heart toward the brain, the intestine, and rest of the body. During inhalation, drugs move from the lungs to the left side of the heart. From there, the drugs move toward the brain, the intestine, and the rest of the body. During oral administration, the drugs move from the intestine to the liver. From the liver, they move into the lungs through the right side of the heart and move out through the left side of the heart toward the brain and the rest of the body. During intramuscular injection, drugs move into the lungs through the right side of the heart and move out through the left side of the heart toward the brain, the intestine, and the rest of the body.

Jump back to Route of Administration

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