Albia Dugger • Miami Dade College

Chapter 5 The Pharmacology

and Physiology of Drug Use

Pharmacology

• Different drugs produce different effects within the psyche and soma

• The interaction between drugs and living organisms is called pharmacology

• Drug pharmacology relates to the way it is administered, absorbed, distributed, metabolized, and excreted

• Drugs that act quickly and produce intense effects are more likely to be abused than are drugs that act slowly

Injected drugs reach the brain quickly

Drug Actions

• Drugs affect various organs, including the nervous system.

• The nervous system consists of the central nervous system (CNS), the autonomic nervous system (ANS), and the peripheral nervous system (PNS)

• The CNS consists of the brain and spinal cord, and is composed of nerve cells (neurons)

• Information is transmitted electrically within the neuron, and chemically between neurons

The Neuron

• Dendrites transmit nerve impulses to the nerve’s cell body (soma)

• Axons send impulses away from the cell body

• Electrical impulses (action potentials) originate in the dendrite and pass through the cell body via the axon

• Between the axon of one neuron and the dendrite of another neuron is a space called a synapse

Neurons in the Brain

The Neuron

• At the ends of axons are saclike vesicles containing neurotransmitters which cross the synapse to receptor sites

• Chemicals in the receptor sites generate electrical impulses

• Drugs that influencing the release, storage, and synthesis of neurotransmitters are classified as presynaptic

• Drugs affecting neurotransmitters after they cross the synapse are classified as postsynaptic

Synaptic Transmission

Drugs and Synaptic Transmission

• Neurotransmitters linked to addiction include dopamine, norepinephrine, GABA, and serotonin

• Some drugs increase activity and excitation nerve cells (e.g. caffeine)

• Sedative-hypnotic drugs make nerve cells less sensitive

• Many nerve cells contain autoreceptors that alter the synthesis of neurotransmitters (e.g. LSD)

Neurotransmitters

• Most drugs affect brain activity by increasing or decreasing the activity of various neurotransmitters

• Neurotransmitters enable the brain to receive, process, and respond to information by carrying impulses from one neuron to the next

Acetylcholine

• Acetylcholine (ACH) • Synthesized from choline and acetyl coenzyme A• Cholinergic neurons are linked to specific behaviors• Excitatory neurotransmitter in skeletal muscles• Inhibitory neurotransmitter in heart muscle• Reduced ACH receptors associated with Alzheimer’s• Anticholinergic hallucinogens interfere with ACH• Cholinesterase inhibitors such as nerve gas

Serotonin

• Serotonin • Inhibitory neurotransmitter in the upper brain stem

(tryptaminergic neurons)• Helps regulate pain, sensory perception, eating, sleep,

and body temperature• Excessive reabsorption results in depression

(antidepressant drugs SSRIs)• Related to hallucinations, psychosis, obsessive-

compulsive disorder, aggression or violence• Amino acid tryptophan is needed to synthesize serotonin

in tryptaminergic neurons

How Drugs Work

Gamma-aminobutyric Acid (GABA)

• Gamma-aminobutyric acid (GABA)• Inhibits nerve impulses from being sent from one neuron

to another• Alcohol stimulates GABA, producing relaxation and

feelings of decreased inhibition• Barbiturates and minor tranquilizers also increase the

action of GABA

Catecholamines

• Catecholamines• Epinephrine, dopamine, and norepinephrine• Reabsorbed by the neuron that makes them (reuptake)• Increase causes stimulation; decrease causes depression• Amphetamines and cocaine initially increase

catecholamines, followed by depletion• Dopamine levels are influenced by marijuana, nicotine,

heroin, and amphetamines• Epinephrine released in fight-flight-fright syndrome• Mescaline and MDMA (Ecstasy) reduce norepinephrine

Fight-Flight-Fright Mechanism

Peptides

• Peptides • Substances in which amino acid sequences are linked• Modulate the activity of transmitters• Natural endorphins have opiate-like properties• High levels of endorphins in the brain (enkaphalins) could

be a factor in morphine dependency• Chronic alcohol use impairs endorphin production

Effects of Selected Neurotransmitters

Central Nervous System (CNS)

• The CNS consists of the brain and spinal cord

• Messages are transmitted from the brain to the muscles and organs and back to the brain through the spinal cord

• The type of message depends on which part of the brain is sending it

Cross Section of the Human Brain

Reticular Activating System (RAS)

• Reticular Activating System (RAS)• Part of the central nervous system• Affects sleep, attention, and arousal• Shuts down during sleep• Many drugs, including barbiturates, LSD, alcohol, and

amphetamines, affect the RAS extensively• Stimulants activate the RAS

Hypothalamus

• Hypothalamus• Gland situated near the base of the brain• Maintains homeostasis• Controls the pituitary gland, which regulates hormones

that affect stress, aggressiveness, heart rate, hunger, thirst, consciousness, body temperature, blood pressure, and sexual behavior

• Linked to behavioral and chemical dependencies from alcohol to gambling to obesity

Cerebral Cortex

• Cerebral cortex• Part of the cerebrum involved in intellectual functioning• Affects speech, motor movement, sensory perception,

hearing, vision, sensory discrimination, memory, language, reasoning, abstract reasoning, and personality

• Affected by almost all psychoactive drugs

Limbic System

• Limbic system • Part of the central nervous system that plays a key role in

memory and emotion• Consists of many diverse structures in the cerebral

hemispheres• Cocaine affects neurotransmitters in the limbic system,

creating intense feelings of excitement and joy• Depressants reduce electrical activity in the limbic system,

producing feelings of tranquility and relaxation

Limbic system Regulates Anger and Hostile Behaviors

Medial Forebrain Bundle

• Medial forebrain bundle (MFB) • Serves as a communication route between the limbic

system and the brain stem• Affects pleasure and reward• Sensation of orgasm originates here• Amphetamines and cocaine produce intense euphoria

Basal Ganglia

• Basal ganglia • Part of the central nervous system which maintains

involuntary motor control• Regulates abilities to stand, walk, run, carry, throw, and lift• Parkinson’s disease destroys the basal ganglia• Drugs prescribed for schizophrenia can precipitate

Parkinson’s-like behavior• China white (fentanyl) has been linked to brain damage

similar to Parkinson’s disease

Periventricular System

• Periventricular System• Composed of nerve cells above and to either side of the

hypothalamus• Implicated in punishment or avoidance behavior• Coupled with the MBF in that stimulation of one inhibits the

other

Brain Stem

• The brain stem is located at the point where the brain and spinal cord join

• It consists of the medulla oblongata, pons, and midbrain

• Regulates functions such as breathing, heartbeat, dilation of the pupil of the eye, blood pressure, and the vomiting reflex

• Drugs affecting the brain stem include alcohol and opiates

Actions of Various Parts of the Brain

Peripheral Nervous System

• Peripheral nervous system (PNS) • Consists of the somatic and autonomic nervous systems

• Somatic nervous system • Part of the nervous system that controls movement of the

skeletal muscles

• Autonomic nervous system (ANS) • Part of the peripheral nervous system that is automatic

and involuntary

Autonomic Nervous System

• The autonomic nervous system (ANS) regulates blood pressure, gastrointestinal and urinary functioning, body temperature, sweating, and other involuntary bodily functions

• Divided into two branches which work in opposition:• Sympathetic nervous system reacts to situations that

require fighting or fleeing (fight-flight-fright syndrome)• Parasympathetic nervous system allows the body to

achieve a resting state

Comparison of Sympathetic andParasympathetic Systems

Autonomic Nervous System

• Drugs that mimic actions of the sympathetic system are called sympathomimetics

• Examples: Amphetamines, cocaine, and caffeine

• Drugs that mimic actions of the parasympathetic system are called parasympathomimetics

• Examples: Nicotine and the hallucinogen Amanita muscaria

Drugs and Major Body Systems

• Endocrine System• Hormones stimulate growth of new tissues, store nutrients,

maintain homeostasis, and affect metabolism and sexual behavior

• The hypothalamus controls the endocrine system and the pituitary gland

• The adrenal glands, secrete adrenaline and cortisol• Many synthetic hormones are used as drugs

Drugs and Major Body Systems

• Cardiovascular System• Drugs that interfere with the heart’s ability to contract

present a danger• Alcohol can cause the heart muscle to degenerate, induce

cardiac arrhythmia, and increase blood pressure• Cocaine increases heart rate and blood pressure, and is a

vasoconstrictor• Cigarettes raise blood pressure and reduce oxygen• Marijuana causes tachycardia

Drugs and Major Body Systems

• Respiratory System• Depressant drugs such as barbiturates, minor

tranquilizers, alcohol, and narcotics slow respiration• Combining depressants with other drugs can have a

synergistic effect• Stimulants such as amphetamines and cocaine increase

respiratory rate• Cigarette smoke impedes cilia from removing mucus and

other foreign matter from the lungs

Drugs and Major Body Systems

• Gastrointestinal System• Antacids containing sodium bicarbonate, calcium

carbonate, aluminum hydroxide, or magnesium salts are used to neutralize stomach acid

• Laxatives are used to relieve constipation• Alcohol causes diarrhea and irritates the stomach, small

intestine, esophagus, and pancreas

Factors Influencing the Effects of Drugs

• Age• Infants and the elderly are more sensitive to the effects of

drugs than people between these two life stages• Drug actions are prolonged because they are less able to

metabolize and excrete drugs• Tolerance for alcohol lessens as people age• Some drugs accumulate in adipose tissue, increasing

sensitivity and the possibility of a toxic reaction• Elementary-age children respond differently to drugs

Elderly use the most prescription drugs

Factors Influencing the Effects of Drugs

• Gender:• Women are more sensitive to drugs because fat stores

drugs and water dilutes drugs in the bloodstream• Females are especially affected by drugs during the

premenstrual phase of the menstrual cycle and pregnancy• Teratogenic drugs damage the developing fetus• Use of tobacco, coffee, and alcohol during pregnancy

increases the risk of miscarriages

Emergency Department Visits by Gender

Males FemalesAll illicit drugs 640,704 352,136Cocaine 306,651 175,465Heroin 138,607 62,018Marijuana 245,553 128,435Stimulants 52,189 39,744MDMA 9,439 8,425

Factors Influencing the Effects of Drugs

• Dosage• The smallest amount of a drug required to produce an

effect is the threshold dose• The amount necessary to achieve a specific response is

the effective dose (ED)• The quantity required to cause death is the lethal dose

(LD)• A dose-response curve represents the effects of drugs at

various levels

Dose-Response Curve

Purity and Potency

• Many problems arise from impurities rather than from the drugs themselves

• The purity of drugs varies greatly among illegal drugs – heroin has varied from 4% to 69%

• Potency refers to a drug’s ability to produce an effect relative to other drugs – some drugs vary naturally in potency

Drug Interactions

• An estimated 25% of admissions to emergency rooms result from interactions between alcohol and medications

• The effects of combining drugs and food can be additive, antagonistic, or synergistic

• Taking certain antidepressants with certain foods can result in hemorrhaging and stroke

• More than 150 prescription and over-the counter medications interact negatively with alcohol

Drug Interactions with Alcohol

Drug Interactions with Alcohol

Tolerance

• Tolerance• Progressively decreasing responsiveness to a drug

• Pharmacological tolerance • Adjustment or compensation of the body to the presence

of a given drug

• Behavioral tolerance • Adjustment or behaviors learned by an individual to

compensate for the presence of drugs

Tolerance

• Cross-tolerance • Transference of tolerance to a drug to chemically similar

drugs

• Reverse tolerance • A drug user’s experiencing of the desired effects from

lesser amounts of the same drug

Set and Setting

• The effects of drugs on behavior depend on one’s attitudes toward drugs, emotional state, and previous experiences

• Set • The psychological state, personality, and expectations of

an individual while using drugs (internal environment)

• Setting • The physical and social environment in which drugs are

used (external environment)

Set and Setting

• Placebos are inert substances capable of producing psychological and physiological reactions

• Placebo prescriptions are effective because of expectations for the drug

• The notion of a drug being euphoric or dysphoric depends a great deal on set

• To a large extent, setting determines set

Methods of Administration

• Oral Ingestion• Drugs can be consumed in the form of pills, liquids,

tablets, or capsules• Convenient and safe• Not appropriate in emergencies • Slow absorption rate may reduce the amount of the drug

to an insufficient level• Can choke on a drug if not conscious• Some ingested drugs cause nausea and vomiting• Because conditions in the gastrointestinal tract change

constantly, drug absorption is variable

Methods of Administration

• Injection (parenteral drug use)• Reach the brain quickly but carry many risks• In intravenous injection, or mainlining, drugs are

administered directly into the bloodstream• In intramuscular injection, drugs are injected into muscle

tissue• Injecting drugs just below the layers of the skin is called

subcutaneous injection• Unsterile needles pose risk for infectious diseases such as

AIDS

AIDS Cases by Transmission Category

Risks associated with injected drug use

Methods of Administration

• Topical application (transdermal method)• Drugs applied to the skin and absorbed into the

bloodstream by placing small disks or patches behind the ear or on the arm or chest

• Introduces drugs into the body slowly• Drugs are absorbed directly into the bloodstream at

programmed rates• Used to relieve motion sickness, angina pectoris, and

nicotine dependency

Methods of Administration

• Inhalation• Drugs absorbed into the bloodstream via the lungs• Fast and efficient• Irritates the lungs• Inhaled drugs include volatile anesthetics such as glue,

paint thinner, and gasoline, in addition to cigarettes, marijuana, and crack cocaine