Learn: Drugs and Behaviors exam #1

Pharmacology

study of drugs

Psychopharmacology

influence of drugs on behavior and psychological function

Neuropharmacology

influence of drugs on brain function

Neuropsychopharmacology

Influence of drugs on brain, behavior and psychological function

Psychoactive drug

a chemical substance that alters perceptions, moods, and consciousness

psychoactive drugs

may be used for recreational, therapeutic, and ritual/spiritual purposes

many ways to classify/categorize drugs

1. Source (natural, synthetic, semisynthetic)

2. Behavioral/psychological effects (including medical/therapeutic use)

3. Pharmacological action

4. Chemical structure

5. Legal status

Drugs have...

multiple pharmacological actions (direct and indirect)

Physical Dependence

The body relies on the drug to prevent withdrawal

addiction

Addiction is defined by uncontrollable cravings , inability to

control drug use, compulsive drug use, and use despite doing

harm to oneself or others. (Classified as a disease)

Addiction can occur...

without physical dependence

Physical dependence can occur ...

without addiction

Physical dependence and addiction can...

co-occur

DSM-5 Substance Use Disorder

use must be maladaptive, meaning it causes harm to the self

Addiction is not

physical dependence and withdrawal

Addiction is

Craving and Relapse

Addiction is defined as

Chronic, relapsing brain disease due to compulsive drug seeking and use, despite harmful consequences. It is considered a brain

disease. Self-control can become seriously impaired.

In the last month, how much of the U.S population has used illicit drugs

13% (Mostly marijuana)

Past year substance use disorder (SUD, addiction)

40.3 million people (14.5%)

Binge drinking

drinking five or more alcoholic drinks at one sitting for men and 4 or more in women

Heavy drinking

5 or more days in the past 30 days

Daily marijuana use is...

On the rise among college students and non-college peers.

Binge alcohol is...

higher in college students than non-college peers.

Marijuana/cannabis vaping

is increasing among college students and non-college peers.

Nicotine vaping

is increasing among college students and non-college peers.

In 2024, non-college peers are vaping cannabis and nicotine...

at higher rates than college students.

Illicit drug use and alcohol has...

decreased in high school students and all grades for alcohol.

Smoking and vaping in high school students has...

Decreased cigarette smoking, but increased vaping for nicotine & THC.

Many Psychoactive substances...

are made by plants and were available to ancient peoples

Which factors shaped drug use and cultural attitudes in the U.S.?

1. The alcohol temperance movement equated drug use with criminal behavior

2. Increased addictive potential of drugs due to advances in chemistry and the development of hypodermic syringes

3. Increased drug availability and lack of drug control laws

4. Medicalization of drug addiction, drug addiction became a disease

Drugs and the law created the...

Controlled Substances Act created 5 schedules of drugs, where Schedule I is considered the most dangerous.

Controlled substances act of 1970

Created by president Nixon in a "war on drugs", Replaced all previous federal drug laws and created the federal drug schedule of controlled substances. Marijuana provisionally placed on Schedule 1 list.

What is the DEA?

Drug Enforcement Agency created in 1973

Under President Reagan...

Harsher penalties for possession and distribution of drugs (including cannabis) and prison populations rose dramatically.

Anti-Drug Abuse Act of 1986

1. Mandatory minimum sentences for drug offenses, including marijuana.

2. Sentencing disparity between crack cocaine and powder cocaine.

3. Strengthened forfeiture laws (Government could confiscate anything in one's possession at the time of a drug arrest)

Anti-Drug Abuse Act of 1988

1. Lowered BAC for DUI to 0.08 (from 0.10)

2. Increased penalties for possession.

What did the war on drugs focus on in the 1990s?

Marijuana " three-strikes" provision for

violent crimes or drugs increased the prison population; during President Clinton's term, jail sentences were 800% higher than in the prior 12 years.

In the 2000s, U.S. drug policies continued for the most part with shifts in policy...

The Fair Sentencing Act was signed by President Obama, reducing cocaine sentencing disparity to 18:1 between penalities of crack and power crack

Who is the top consumer of illicit drugs?

America

The past aproach to the drug problem has been:

1. Drugs are a criminal justice problem.

2. Law enforcement

3. Penalization

How much influence has science had on the nation's drug policy?

A little bit

What is a future approach to the drug problem?

1. Drugs are a public health problem.

2. Increased treatment and education

3. Focus on harm reduction

Harm Reduction Strategies using facilites

Education to the public: Dispel myths that these strategies facilitate substance use. Harm reduction services are cost-effective and save money.

Pharmacokinetics

Absorption, distribution, metabolism, and

excretion of drugs. How does a drug move in the body?

Pharmacodynamics

biochemical effects of drugs and their

mechanism of action. How does a drug change the body?

ADME

absorption, distribution, metabolism, excretion; Pharmacokinetic factors affect the amount of drug available to bind to target sites and elicit drug action, they deterim a drugs onset, duration and peak concentration.

Pharmacokinetic factors compete and work

simultaneously

Absorption into blood circulation

Factors affecting absorption:

1. Route of administration

2. Drug solubility and ionization

Oral (peroral, PO)

-absorption in gastrointestinal tract

-slow, variable

-first-pass metabolism in the liver (& GI system) before entering bloodstream

Which routes typically avoid first-pass metabolism?

intranasal, inhalation, sublingual, rectal, and transdermal

Most common injections

subcutaneous, intramuscular, intravenous

Different routes give different drug

1. onset

2. peak concentration

3. duration

Medical applications vs drug abuse

Medical routes are slow and drug abuse is faster routes to achieve the highest peak concentration with rapid onset

Oral or transdermal

slow absorption

Intravenous (IV) injection or inhalation/smoking

Fast onset of drug action

increased addictiveness associated with

fast onset and short duration of action

Route of Administration affecting absorption rate

Blood circulation and surface area of the site, digestive/metabolic processes, transport across membrane (number of cell layers to blood)

Properties of the drug affecting absorption rate

solubility and ionization

Molecules/drugs easily diffuse across membranes when they are:

Lipid soluble, and non-ionized

heroin versus morphine: lipid solubility

Heroin (taken IV) reaches the brain much faster than morphine.

Most drugs are weak acids or weak bases and they tend to become

ionized when dissolved in water (neutral pH)

ionized drugs are not readily

lipid soluble

different body fluids have different pH, which will

affect drug ionization.

ion trapping

concentration of the drug in one compartment

Distribution

Movement from blood to target site

Distribution to the brain is affected by the

Blood-brain barrier and depot binding

BBB is selectivly

permeable (lipophilic)

Some exceptions are areas with weak BBB

Area postrema (vomiting center) and median eminence (hormones into blood)

Depot binding of drug can occur where

albumin (plasma), fat, and muscle

Depot binding is

Inactive state (while bound), Protected from metabolism, affects peak and duration of drug concentration

Example of depot binding of THC in fat

leads to slow release, such that THC is detected in urine many days after a single dose.

Metabolism and excretion

movement out of system

where is drug inactivation usually?

metabolism (a.k.a. biotransformation), particularly in the liver by microsomal enzymes

Phase 1 metabolism

Oxidation, reduction, hydrolysis (non-synthetic reactions)

Phase II Metabolism

1. Addition of small molecules such as glucuronide, sulfate, or methyl groups (synthetic reactions)

2. Products (metabolites) are ionized and less lipid-soluble, so usually biologically inactive (i.e.,

inactive metabolites).

Active metabolites

have biological activity of their own and

still need further metabolism to become inactive metabolites.

First-order kinetics

Exponential rate = most common and has a half-life (me for

plasma drug concentration to fall to half of the peak level)

Zero-order kinetics

Constant rate = (linear) because metabolism/excretion

processes are saturated. (alcohol is an example)

Another way to say pharmacodynamics is:

Action of drug at receptors or targets.

Ligand

a neurotransmitter or drug that fits a given receptor

Receptor

The protein that a ligand interacts with to initiate its biological

effects; receptors recieve and transduce signals

Drug effect

Drug + receptor

Agonist

ligands that bind to receptor and initiate a cellular response

anatagonists

Ligands that bind to receptor and cause no cellular response; they block the action of an agonist or endogenous ligand (e.g., a

neurotransmitter) at the same receptor

Neurotransmitters, agonists, and antagonists tend to form weak non-covalent

interactions with receptors that are readily

reversable

Membrane-bound receptors

A drug may be more specific for the receptor than the endogenous neurotransmitter (drugs can show agonist or antagonist actions)

Drugs do not produce new or unique cellular responses

They mimicking, increasing, or inhibiting normal physiological/biochemical processes.

Drug-receptor binding is

temporary and reversible

The speed of dissociation is determind by

binding affinity of the drug for the receptor

law of mass action

More drug molecules = increased receptor occupancy.

Maximum drug effect = when all receptors are occupied.

The cellular response is proportional to the degree of receptor occupancy. This relationship is described by the dose-response curve.

ED100

Effective dose that gives maximum response and all receptors are occupied

ED50

dose that produces half the maximum effect

A dose-response curve

has a "sigmoid" (S) shape when plotted on a semi-log scale.

therapeutic index

TD50 = dose that produces a given toxic effect in 50% of subjects

LD50 = dose that kills 50% of subjects (lethal dose)

Therapeutic Index (TI, margin of safety) = LD50 / ED5

Potency vs Efficacy

potency: amount of drug necessary to produce the desired effect

efficacy: maximum effect that can be produced by a drug

Why do some drugs have a higher potency than others?

Pharmacokinetic factors play a role; drugs may have different binding affinity for those receptors, Binding affinity does not determine the maximum possible effect

Why do some drugs have higher efficacy than others?

They may act by different mechanisms (e.g., different receptors), and they may have different activity at the same receptor, once bound

Competitive antagonists

bind to same receptor binding site as agonist; Antagonist effect can be overcome by adding more of the agonist; Shifts dose-response for agonist to the right.

Non-competitive antagonists

Does not compete with the agonist for the receptor binding site; Antagonism cannot be overcome. Shifts the dose-response curve for the agonist to the right, but also changes its shape

Efficacy of partial agonist

is lower than full agonist, higher than antagonist; In the presence of full agonists, they can act as antagonists