Drugs and Human Behavior Chp 4 & 5

Absorption

Passage of a drug from the site of administration to the bloodstream

Liberation

Process of drug molecules separating from the pill or solution in which it was delivered

Distribution

The passage of a drug from the bloodstream to sites in the body

Bioavailability

Ability of a drug to reach a site of action

Blood-Brain Barrier

Barrier that surrounds the blood capillaries and vessels in the brain and prevents substances in blood from entering the brain

Passive Diffusion Through Blood-Brain Barrier

Blood-brain barrier penetration by lipid-soluble, uncharged, small substances

Active Transport Through Blood-Brain Barrier

Mechanisms consisting of channels or other types of proteins that transport chemicals through endothelial cell membranes

Nonspecific Binding

Binding of a drug to sites that are not the intended target for a drug's effects

Biotransformation

Process of converting a drug into one or more metabolites

Metabolite

Product resulting from enzymatic transformation of a drug

Phase I Biotransformation

First biotransformation phase for a drug that normally involves P450 enzymes and produces a water-soluble metabolite

Phase II Biotransformation

Second biotransformation phase occurring through conjugation of a drug's metabolites, making them resistant to passive diffusion

Personalized Medicine

Method of prescribing treatments most appropriate for a patient's unique biological makeup

First-Pass Metabolism

Drug metabolism that occurs prior to absorption into the bloodstream

Active Metabolite

A drug's metabolite that has physiological effects

Prodrug

A physiologically weak or inactive compound metabolized in the body to produce an active drug

Elimination

Process for how a drug leaves the body

Elimination Rate

Amount of drug eliminated from the body over time

Half-Life

Duration of time necessary for the body to eliminate half of a drug

First-Order Kinetics

The elimination of a drug in half-lives

Zero-Order Kinetics

The elimination of a drug in non-half-lives

Pharmacodynamics

Mechanisms of action for a drug

Binding Affinity

Drug's strength of binding to a receptor

Receptor Efficacy

Drug's ability to alter the activity of a receptor

Agonist

Drug that activates a neurotransmitter receptor

Antagonist

Drug that fails to activate a receptor

Partial Agonist

Drug that possesses a weaker efficacy for activating receptors than a full agonist

Competitive Antagonist

Drug that binds to the same site as a neurotransmitter, preventing a neurotransmitter from binding to the receptor

Noncompetitive Antagonist

Drug that does not prevent a neurotransmitter from binding to the receptor but does prevent the neurotransmitter from activating the receptor

Allosteric Regulator

A substance that binds to a site on a protein and causes a conformational change in the protein, but neither activates nor prevents activation of the protein

Positive Modulator

A chemical substance that binds to an allosteric site on a receptor and increases the ability of a neurotransmitter to bind to and/or activate the receptor

Negative Modulator

A chemical substance that binds to an allosteric site on a receptor and decreases the ability of a neurotransmitter to bind to and/or activate the receptor

Neurotoxins

Substances that damage or destroy parts of the nervous system

Environmental Neurotoxicology

A field devoted to the study of neurotoxins in the environment

Tolerance

Occurs when a user must take greater doses of a drug to achieve desired effects

Pharmacokinetic Tolerance (or Drug Dispositional Tolerance)

Pharmacokinetic actions that reduce the amount of drug reaching its site of action

Pharmacodynamic Tolerance

Reduced responsiveness to a drug at the drug's site of action

Behavioral Tolerance

Decreased behavioral responsiveness to a drug's effects

Conditioned (or Contingent) Tolerance

Occurs as a physiological response to stimuli associated with substance use that serves to counteract a drug's physiological actions

Cross Tolerance

Tolerance for other drugs with similar biological actions

Sensitization

Increased responsiveness to a drug's effects

Dependence

Needing a drug to be able to function normally

Withdrawal Syndrome

The collection of withdrawal symptoms for a drug

Physical Dependence

Presence of physical withdrawal symptoms when a drug is not taken

Psychological Dependence

Presence of psychological withdrawal symptoms when a drug is not taken

Pharmacokinetic Properties

What the body does to a drug, including liberation, absorption, distribution, biotransformation, and elimination.

Route of Administration and Absorption

The route affects how much drug reaches the bloodstream and how quickly; intravenous administration is rapid and highly bioavailable, while oral administration is slower and may be reduced by first-pass metabolism.

pKa

The pH at which half of a drug is ionized and half is nonionized; it helps predict membrane crossing and absorption.

Factors Influencing Bioavailability

Route and formulation, membrane absorption, lipid solubility, ionization, blood flow, metabolism, and binding can affect how much active drug reaches its site of action.

Active Metabolism

Metabolism that converts a drug into an active metabolite or produces physiologically active products.

Steady State

A condition in which the average amount of drug entering the body equals the average amount eliminated, producing a stable average concentration.

Importance of Steady State

Maintains drug concentrations within the therapeutic range and produces more consistent treatment effects.

Drug Actions on Neurotransmission

Drugs can alter neurotransmitter synthesis, storage, release, receptor binding, receptor activation, reuptake, enzymatic breakdown, and intracellular signaling.

Radioligand Binding

A technique using a radioactively labeled ligand to measure receptor binding, affinity, and receptor density.

[35S]GTPgammaS Binding Assay

A technique that measures G-protein activation by tracking radioactive [35S]GTPgammaS binding to activated G proteins.

Tetrabenazine

A VMAT2 inhibitor that reduces monoamine storage and release, especially dopamine; it is used to reduce chorea.

Bicuculline

A competitive GABA-A receptor antagonist that blocks inhibitory signaling, increases neuronal excitability, and can produce seizures.

U.S. Drug Regulatory Agencies

The Food and Drug Administration (FDA) regulates medication approval and safety, while the Drug Enforcement Administration (DEA) enforces controlled-substance laws.

Controlled Substances Schedule I

Drugs with high abuse potential, no currently accepted medical use in the United States, and a lack of accepted safety under medical supervision.

Controlled Substances Schedule II

Drugs with high abuse potential but accepted medical uses; abuse may cause severe psychological or physical dependence.

Controlled Substances Schedule III

Drugs with lower abuse potential than Schedule I or II drugs; abuse may cause moderate or low physical dependence or high psychological dependence.

Controlled Substances Schedule IV

Drugs with lower abuse potential than Schedule III drugs and limited risk of dependence.

Controlled Substances Schedule V

Drugs with the lowest abuse potential among controlled substances; they may contain limited amounts of certain narcotics.

Harm Ratings

A classification system that ranks drugs according to their potential for physical, psychological, and social harm; harm ratings differ from legal scheduling because they focus on overall harm rather than legal status and medical use.

Substance Use Disorder (DSM-5)

A problematic pattern of substance use causing clinically significant impairment or distress, diagnosed when multiple behavioral, physical, and social criteria occur within a specified period.

Unconditioned Stimulus

A stimulus that naturally produces a response without prior learning; in addiction research, the drug's effects may function as an unconditioned stimulus.

Self-Administration Procedure

A drug-research procedure in which an animal performs a response, such as pressing a lever, to receive a drug. Repeated responding indicates that the drug reinforces behavior.

Reward Circuitry of the Brain

Drug effects commonly involve dopamine neurons from the ventral tegmental area projecting to the nucleus accumbens and other limbic and cortical regions, including the prefrontal cortex.

Chronic Drug Use and Learning

Chronic substance use can strengthen drug-related associations and make drug cues increasingly powerful, while reducing the ability of ordinary rewards to control behavior.

Chronic Drug Use and Memory

Chronic substance use can impair memory systems, especially hippocampal functioning, and shift behavior toward habitual, drug-seeking responses.

Dorsal Striatum

A brain area involved in habit learning and the transition from goal-directed drug seeking to more automatic, habitual drug-seeking behavior.

Hippocampus (Role in Drug Addiction)

Associates environmental contexts and memories with drug use, allowing drug-related places and situations to trigger craving and relapse.

Stages of Drug Addiction

Addiction is commonly described as binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Each stage involves different behavioral and neurobiological processes.

Binge/Intoxication Stage

The individual experiences the rewarding or reinforcing effects of the drug and may engage in repeated drug use.

Withdrawal/Negative Affect Stage

The individual experiences negative emotional and physical symptoms when the drug is absent and may use the drug to relieve those symptoms.

Preoccupation/Anticipation Stage

The individual experiences craving and preoccupation with obtaining or using the drug, increasing the risk of relapse.

Therapy Approaches

Drug addiction treatment may combine psychological therapies, such as cognitive-behavioral therapy and 12-step programs, with pharmacological approaches, such as detoxification and drug-replacement therapy.

Controlled Substances Schedules Versus Harm Ratings

Controlled-substance schedules are legal categories based mainly on abuse potential, accepted medical use, and safety. Harm ratings estimate overall harm and may rank legal drugs as highly harmful or illegal drugs as less harmful than their legal status suggests.