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The Actions of Drugs – Smart Essays

Chapter 5

The Actions of Drugs

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Chapter Objectives

After reading this chapter, students should be able to:

· Explain why plants produce so many of the chemicals we use as drugs.

· Distinguish among generic, brand, and chemical names for a drug.

· Understand and describe the typical effects of drugs in each of six categories.

· Understand the importance of placebo effects and the necessity of double-blind studies.

· Define and explain dose-response relationship, ED50, LD50, and therapeutic index.

· Explain why pharmacological potency is not synonymous with effectiveness.

· Compare and contrast the most important routes of drug administration.

· Explain the potential influence of protein binding on interactions between different drugs.

· Describe ways psychoactive drugs interact with neurons to produce effects in the brain.

· Explain the role of homeostatic mechanisms in pharmacodynamic tolerance and withdrawal symptoms.

Chapter Vocabulary (in order of appearance in chapter)

5-7

chemical name

generic name

brand name

stimulant

depressant

opioid

analgesic

hallucinogen

psychotherapeutic

antipsychotic

neuroleptic

antidepressant

placebo

placebo effect

nonspecific effect

specific effect

double-blind procedure

dose-response curve

threshold

ataxia

comatose

PETA

effective dose (ED)

lethal dose (LD)

ED50

LD50

therapeutic index (TI)

safety margin

side effect

potency

time course

cumulative effects

lipid solubility

intravenous (IV)

subcutaneous

intramuscular

inhalation

blood-brain barrier

synapse

availability

receptor

metabolite

active metabolites

prodrugs

tolerance

drug disposition tolerance

behavioral tolerance

pharmacodynamic tolerance

Chapter Outline

I. Sources and Names of Drugs

A. Most drugs are derived directly or indirectly from plants.

B. Names of drugs

1. Chemical name

a. Complete chemical description of the molecule

b. Based on rules of organic chemistry for naming a compound

2. Generic name

a. Official (legal) name of drug listed in the United States Pharmacopoeia

b. Shorter and simpler version of the chemical name

c. Cannot be trademarked (in public domain)

3. Brand name

a. The brand name specifies a particular formulation and manufacturer.

b. It is trademarked (copyrighted) by a specific manufacturer.

c. A new chemical structure, new way of manufacturing a drug, or new use for a chemical can be patented for 20 years.

d. Once a patent expires, other manufacturers can produce and sell a drug, although they must use the generic name or their own brand name.

e. When a drug “goes generic,” the original manufacturer might reduce the price of the drug or develop new formulations of the drug.

II. Categories of Drugs

A. Stimulants produce wakefulness and a sense of energy.

B. Depressants slow the activity of parts of the nervous system.

C. Opioids (narcotics) reduce pain.

D. Hallucinogens produce altered perceptions.

E. Psychotherapeutic drugs are used to control mental disorders.

1. Antipsychotics

2. Antidepressants

F. Marijuana and nicotine are difficult to classify because they have effects typical of more than one category of drugs; each has its own category.

G. It is important that both legal and illicit drugs be identifiable by appearance.

H. The Physician’s Desk Reference (PDR) includes color photographs of many legally manufactured pharmaceuticals.

I. Illegal drugs are sometimes shaped or marked in an identifiable way.

J. Drugs can be tested and identified through chemical analysis.

IV. Drug Effects

A. Nonspecific (placebo) Effects

1. Nonspecific effects are influenced by expectations, experience, and setting, and are derived from the user’s unique background and perceptions.

2. Placebo effects are those produced by an inactive chemical that the user believes to be a drug.

3. Placebo effects are real effects and have been shown to be especially important in treating pain and psychological depression.

4. To determine the effectiveness of a drug, double-blind tests are needed; in a double-blind procedure, neither the test subjects nor the person evaluating the drug’s effect knows whether a person is receiving a placebo or the experimental drug until the trial is over.

5. Specific effects are those that depend on the presence of the chemical at certain concentrations.

B. Dose-response Relationships

1. A dose-response relationship is a strong demonstration of specific drug effects.

2. A dose-response relationship means there is a correlation between the response and the quantity of drug administered.

3. A dose-response curve graphs the size of a response to the amount of drug administered.

4. The dose at which an effect is first observed is called the threshold.

5. Some response systems have higher drug thresholds than others, so dose-response curves can be created for different drug effects.

6. Some drugs have an all-or-none effect.

C. Effective and Lethal Doses and the Margin of Safety

1. An effective dose is the dose of a drug that produces an effect in some percentage of test subjects; ED50 refers to the effective dose for half the animal subjects in a drug test.

2. A lethal dose is the dose of a drug that has a lethal effect in some percentage of test subjects; LD50 refers to the lethal dose for half the animal subjects in a drug test.

3. Therapeutic index is defined as LD50/ED50.

4. The safety margin is the difference between the dose that produces the desired therapeutic effect in most patients and the lowest dose producing some unacceptable toxic reaction.

5. For human use of drugs, side effects are usually considered in setting upper dosage limits; if the number or severity of side effects is great, a drug will be discontinued or the dose lowered even if it is effective.

D. Potency

1. Potency is the amount of a drug that must be given to obtain a particular response.

2. Potent drugs produce effects at very low doses.

E. Time-dependent Factors in Drug Actions

1. Drugs vary in the timing of the onset, duration, and termination of their effects.

2. The time course of a drug depends on how the drug is administered, how rapidly is it absorbed, and how it is eliminated from the body.

3. Drug effects can be prolonged by taking additional doses at intervals determined by the time course of the drug.

4. Taking multiple doses too close together will increase the maximum blood level of the drug and can result in cumulative effects.

V. Getting the Drug to the Brain

A. A Little “Chemistry”

1. Lipid solubility refers to the tendency of a chemical to dissolve in fat as opposed to in water.

2. Most psychoactive drugs dissolve to some extent in both water and lipids, but lipid solubility is important for certain routes of administration (especially oral ingestion).

B. Routes of Administration

1. Oral ingestion

a. Absorption from the gastrointestinal (GI) tract is a complicated process.

b. Chemicals must withstand the digestive processes and get through the cells lining the GI tract into the bloodstream.

c. Drugs from the GI tract travel through veins first to the liver; those drugs that are rapidly metabolized by the liver may thus enter the general circulation in only very small amounts.

2. Injection—delivered with a hypodermic syringe

a. Intravenous (IV) injection involves putting the drug directly in the bloodstream.

(1) Effects are rapid.

(2) High concentrations can be delivered.

(3) Veins can be damaged over time.

(4) Infections can be directly introduced into the bloodstream.

b. Subcutaneous injection (under the skin) and intramuscular injection (into a muscle) have similar characteristics, except that absorption is more rapid from intramuscular injection due to the greater blood supply in muscles.

3. Inhalation

a. The drug moves from the lungs into the bloodstream through capillary walls.

b. Effects are rapid because blood moves fairly quickly from the lungs to the brain.

4. Topical application

a. Absorption through the skin can provide slow, steady drug delivery.

b. Absorption through the mucous membranes occurs more rapidly.

C. Transport in the Blood

1. Some drug molecules attach to protein molecules; they are inactive in this state.

2. Free (unbound) drug molecules can move to sites of action in the body.

3. Drugs vary in their affinity for binding with plasma proteins.

D. Blood-brain Barrier

1. Some classes of compounds are blocked from crossing the blood-brain barrier and act only on neurons outside the central nervous system.

2. Only lipid-soluble substances can leave capillaries in the brain because brain capillaries, unlike capillaries in other parts of the body, have no pores.

3. Many brain capillaries are covered with glial cells, also increasing the difficulty for compounds to pass out of the capillaries.

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

5. Trauma and infections can impair the blood-brain barrier.

VI. Mechanisms of Drug Action

A. Effects on All Neurons

1. Chemicals that affect all neurons influence a common characteristic, such as the permeability of the cell membrane.

B. Effects on Specific Neurotransmitter Systems

1. Different psychoactive drugs produce different types of effects by interacting in different ways with neurotransmitter systems in the brain.

a. Drugs may alter the availability of a neurotransmitter by changing the rate of synthesis, metabolism, release, or reuptake.

b. Drugs may activate or prevent the activation of a receptor.

C. Drug Interactions

1. Combining depressant drugs can cause dangerous, or even fatal, respiratory depression.

2. Combining stimulants and antidepressants can lead to overexcitement, high blood pressure, and irregular heartbeat.

3. Combining stimulants and depressants can lead to explosive and dangerous behaviors.

4. Combining cocaine and alcohol produces a stimulant called cocaethylene, which has similar but less potent effects than cocaine.

VII. Drug Deactivation

A. A drug ceases to have an effect when it is excreted unchanged from the body (usually in urine) or it is chemically changed.

B. A common process for deactivation is for enzymes in the liver to change the chemical structure of the drug; the most important drug-metabolizing liver enzymes are in a group known as CYP450.

1. The resulting metabolite no longer has the same action as the drug.

2. The resulting metabolite can be excreted by the kidneys.

C. Enzyme induction occurs when the body’s cells detect the presence of a foreign drug molecule; they trigger production of more of the specific enzyme that metabolizes the drug.

1. Enzyme induction plays a role in tolerance.

2. Enzyme induction plays a role in interactions of drugs that are broken down by the same enzyme.

3. Enzyme activity returns to normal some time after the inducing drug is no longer being used.

4. Enzyme induction can affect the action of therapeutic drugs and can be induced by prescription and over-the-counter drugs and dietary supplements as well as by illicit drugs.

D. Some Drugs Produce Active Metabolites

1. Active metabolites produce effects similar to the original drugs and prolong the effects.

2. Prodrugs become active only after they are altered by liver enzymes.

VIII. Mechanisms of Tolerance and Withdrawal Symptoms

A. Drug Disposition (Pharmacokinetic) Tolerance

1. Occurs when use of a drug increases the rate of metabolism or excretion

2. May relate to enzyme activity or alteration of urine pH

B. Behavioral Tolerance

1. Occurs when individuals learn to compensate for nervous system impairment

2. Drug may have the same biochemical effect but a reduced behavioral effect

C. Pharmacodynamic Tolerance

1. Occurs when the sensitivity of neurons to a drug changes

2. May relate to changes in neurotransmitter production or receptor numbers

3. Can cause withdrawal reactions

Key Points

· Many drugs come directly from plants or are chemically derived from plant substances.

· In the United States, sales of legal pharmaceuticals exceed $189 billion per year.

· All commercially available drugs have at least three categories of names. The chemical name is the complete chemical description of the molecule. Most will never know or understand this name of a drug they are taking. The generic name of a drug is the legal name of the drug, usually a simpler version of the chemical name. The brand name is for a specific formulation and manufacturer. The big difference between the generic name and the brand name is that a generic name is public domain while a brand name is trademarked by the company that developed the drug. The developing company gets to name the drug but it must be approved FDA.

· Categories of psychoactive drugs (in Figure 5.1) are stimulants, hallucinogens, marijuana, depressants, opioids, psychotherapeutics, and nicotine.

· Each drug has defining characteristics that separate it from others.

· The Physician’s Desk Reference has color photographs of most legally manufactured drugs; it also includes information like dose and potency.

· The placebo effect is usually thought of in terms of an inactive (“sugar”) pill.

· Many drugs effects are influenced by the user’s experiences, mood, expectations, and factors such as what food and other drugs she or he has consumed.

· The dose-response relationship refers to the correlation between the quantity of drug administered and the size of the effect. The response may vary due to factors such as tolerance.

· Dose-response curves help provide information on effective and lethal doses.

· Toxicity, in early animal studies, is measured in how many animals die as a result of taking the drug. After more studies, the therapeutic index is set as LD50/ED50.

· The margin of safety is the difference between the doses necessary for an intended effect and the dose above which toxic side effects occur.

· Potency refers to the amount of drug necessary to cause an effect, while toxicity is the capacity of a drug to upset or destroy normal body functions.

· The forms and methods of taking drugs greatly influence how the drugs will interact with the user’s system. Oral ingestion is a simple way to take a drug, but absorption via the GI tract is a complicated process. Inhalation is when the drug is smoked or “huffed”; the drug moves very quickly into the blood via absorption through capillaries in the lungs. Nicotine, marijuana, and crack are most effective when delivered this way. Injection can occur in several ways—directly into a vein (intravenous), under the skin (subcutaneous), or into a muscle (intramuscular); intravenous injection results in the most rapid effects.

· Topical application is not used as often because many drugs are not absorbed effectively through the skin.

· After drug administration, the body eliminates the drug through metabolism and excretion.

· The drug will either leave the system or be changed so much that it will no longer have an effect on the body.

· Prodrugs have been developed to start working only after they have been altered by the body.

· The body has adaptive processes, such as tolerance, to protect against potential harm.

· With drug disposition tolerance, the more the drug is used, the faster the metabolism or excretion.

· Behavioral tolerance occurs when a drugs has the same biochemical effect but a reduced behavioral effect because the user has learned to compensate for some of the behavioral effects of the drug.

· Pharmacodynamic tolerance occurs when the sensitivity of neurons to a drug changes; if drug use stops, withdrawal reactions can occur because the nervous system has adapted its functioning to the drug.

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