Exam 2 Study Guide: M216 -- the Medical Science of Psychoactive Drugs

Cross tolerance

Developing tolerance to one drug results in tolerance to another drug in the same class.

Cross dependence

One drug can suppress withdrawal symptoms caused by stopping another drug.

Cross tolerance vs. cross dependence

Cross tolerance transfers tolerance within a drug class; cross dependence suppresses another drug's withdrawal.

Metabolic tolerance

Liver enzymes increase in number or efficiency, causing a drug to be broken down faster.

What happens to liver enzymes during metabolic tolerance?

They up-regulate.

Behavioral tolerance

An experienced drug user learns to compensate for drug effects and may appear more normal while intoxicated.

Example of behavioral tolerance

An intoxicated person deliberately focuses on walking straight because alcohol impairs balance.

Pharmacodynamic tolerance

CNS/receptor changes make the body less responsive to a drug after prolonged use.

What happens to receptor sensitivity during pharmacodynamic tolerance?

Sensitivity decreases; receptors down-regulate/desensitize to maintain homeostasis.

Classical/Pavlovian conditioning and drugs

Environmental cues associated with drug use can trigger drug-related responses without taking the drug.

Example of drug-related classical conditioning

Needles, paraphernalia, or old drug-use locations can trigger responses or contribute to relapse.

Drug sensitization

Increased responsiveness to drug-associated cues; often described as the inverse of tolerance.

Tolerance vs. sensitization

Tolerance = less response; sensitization = more response.

How can classical conditioning affect drug sensitization?

Drug-associated cues can increase sensitization and trigger cravings.

Physical dependence

Stopping a drug produces physical withdrawal symptoms.

Abstinence syndrome

The set of withdrawal symptoms such as nausea, shaking, headaches, insomnia, vomiting, anxiety, and depression.

Neurotransmitter-receptor bonds

Usually ionic, meaning weak and temporary.

Ionic vs. covalent bonds

Ionic bonds are weak and temporary; covalent bonds are strong and permanent.

Three ways substances are removed from a synapse

Glial-cell reuptake; presynaptic reuptake channels; enzymatic degradation.

Glial cells in synaptic cleanup

Specialized cells that help remove substances from the synapse through reuptake.

Rat Park experiment

Isolated rats preferred morphine water more than rats living in an enriched, social environment.

Main lesson of Rat Park

Environment matters in drug use and addiction.

Genetics + environment in addiction

Genetic predisposition can influence addiction, while environment can also have an important impact.

Disease model of addiction

Drug use can progress from impulsive to compulsive behavior as repeated exposure alters reward processes.

Disease model progression

Recreational use → impulsive use → repeated use → withdrawal → preoccupation/anticipation → compulsive use.

Positive reinforcement in drug use

Repeated use occurs because the drug produces rewarding effects.

Negative reinforcement in drug use

Continued use occurs to avoid or relieve unpleasant withdrawal effects.

Drug salience

Things outside obtaining and using the drug become less relevant; even the drug can become less rewarding.

Why does the brain down-regulate receptors with repeated drug use?

To maintain homeostasis after unusually large drug-induced reward signaling.

Repeated drug use and reward receptors

Receptors become desensitized/down-regulated, contributing to pharmacodynamic tolerance.

Stress during drug withdrawal

Stress and dysphoria increase, encouraging continued use to avoid withdrawal symptoms.

CRF

Corticotrophin-releasing factor; a central driver of the stress response.

When is CRF elevated in addiction?

During withdrawal, contributing to an enhanced stress response.

Effects of CRF

Suppresses appetite, increases anxiety, and improves memory/selective attention for stressful events.

CRF and the pituitary gland

CRF works with the pituitary gland, where ACTH is released.

ACTH

Adrenocorticotropic hormone.

CRF and sympathetic activity

CRF contributes to increased sympathetic activation.

Amygdala

Brain region strongly associated with fear and the stress response.

Alcohol absorption

According to the guide, 100% of alcohol gets absorbed.

Blood alcohol vs. breath alcohol levels

The guide describes them as about the same in number.

What air does a breathalyzer measure?

Expired/exhaled air from deep in the lungs.

Why can breath alcohol indicate BAC?

Thin alveoli allow alcohol to diffuse from blood into alveoli for measurement in expired air.

Alcohol solubility

Both water soluble and lipid soluble.

Alcohol decline rate

About 0.015 g% per hour.

Does alcohol have a half-life?

No; the guide describes alcohol elimination as zero-order kinetics.

Why can alcohol decline rates differ?

Individual metabolic tolerance can affect decline rate.

Alcohol metabolism sequence

Alcohol → acetaldehyde → acetic acid → CO2 + H2O + energy.

Alcohol dehydrogenase

Enzyme that converts alcohol into acetaldehyde.

Acetaldehyde

Toxic product formed during alcohol metabolism.

Acetaldehyde/aldehyde dehydrogenase

Enzyme that converts acetaldehyde into acetic acid.

What happens if acetaldehyde is not broken down efficiently?

It accumulates and can cause vomiting, flushing, headache, and increased heart rate.

Low-activity aldehyde dehydrogenase

Acetaldehyde accumulates, causing unpleasant/toxic effects.

What does the suffix -ase usually indicate?

An enzyme.

Alcohol metabolic tolerance

Liver enzymes become more efficient/specific and/or increase in number with continuous heavy use.

Alcohol pharmacodynamic tolerance

Receptors become less sensitive or responsive to alcohol.

Alcohol's two major receptor effects

GABA agonist + glutamate antagonist.

Alcohol and GABA

Alcohol acts as a GABA agonist, contributing to depressed brain function.

Alcohol and glutamate

Alcohol acts as a glutamate antagonist, decreasing memory, cognition, and overall brain activity.

Why is alcohol a depressant?

Increased GABA effects plus decreased glutamate effects produce overall CNS depression.

Biphasic response of alcohol

Initially stimulant-like; around BAC 0.05, depressant effects begin.

Early/stimulant phase of alcohol

The guide associates it with the VTA and NA reward/pleasure centers.

Later/depressant phase of alcohol

Increasing alcohol produces stronger GABA-related depressant effects.

Alcohol withdrawal and glutamate

Glutamate activity increases, making the brain more excitable.

Symptoms from increased glutamate during alcohol withdrawal

Shaking, anxiety, insomnia, and severe cases can include seizures.

Fatty liver

High alcohol levels impair fat metabolism, causing fat deposits in liver tissue.

How quickly can fatty liver occur?

According to the guide, after as little as 10 days of binge drinking.

Is fatty liver reversible?

Yes, if the person stops drinking.

Symptoms of fatty liver

The guide states there may be no signs or symptoms.

Alcoholic hepatitis

Acute liver inflammation associated with excessive alcohol use; it can be fatal.

Mechanism described for alcoholic hepatitis

Gut bacteria leak through alcohol-damaged intestines, reach the liver, and trigger inflammation and scar formation.

Alcoholic hepatitis symptoms

Lethargy, nausea, vomiting, diarrhea, abdominal pain, fever, and jaundice.

Alcoholic hepatitis treatment in the guide

Detoxification and anti-inflammatory medication such as prednisone.

Alcoholic cirrhosis

Years of excessive drinking cause fibrous scar tissue that impairs liver function.

Cirrhosis: acute or chronic?

Chronic.

Why does cirrhosis impair liver function?

Scar tissue obstructs blood flow and reduces effective healthy liver function.

Is cirrhosis reversible?

The liver can regenerate, but the guide says cirrhosis becomes irreversible after a point.

Portal hypertension

Increased portal-vein pressure caused when liver scarring interferes with normal blood flow.

Why does cirrhosis cause portal hypertension?

Scar tissue obstructs blood flow, causing blood to back up and pressure to rise.

Venous dilation in portal hypertension

Veins enlarge, making leakage more likely.

Ascites

Accumulation of capillary fluid in the abdomen associated with portal hypertension.

Is ascites accumulated blood?

No; it is fluid, not blood.

Esophageal varices

Bulging veins in the esophagus resulting from portal hypertension.

What can happen when esophageal varices rupture?

The person may vomit blood or have bloody stool.

Vitamin K deficiency and alcoholism

Vitamin K supports clotting; deficiency can impair clotting and increase bleeding.

Malnutrition associated with alcoholism

Heavy drinking may replace nutritious food and lead to vitamin deficiencies.

Fetal Alcohol Syndrome (FAS)

Craniofacial abnormalities, cognitive deficiencies, growth deficiencies, and behavioral issues.

Most common issue listed for FAS

Behavioral issues.

Treatment for FAS according to the guide

No treatment reverses it; symptoms are managed with therapy and/or medication.

Acute alcohol withdrawal symptoms

Shakes, anxiety, irritability, nausea, craving, vomiting, headaches, insomnia, and possible seizures.

Medication used for acute alcohol withdrawal

Benzodiazepines.

Why are benzodiazepines useful in acute alcohol withdrawal?

They enhance GABA activity and act as anticonvulsants to control symptoms and seizures.

Concern with benzodiazepines during alcohol withdrawal

They treat withdrawal with another drug that has dependence/abuse concerns.

Advantage of benzodiazepines in withdrawal treatment

The dosage can be titrated appropriately.

Chronic alcohol withdrawal

Cravings can persist long after physical dependence/addiction and may last a lifetime.

Alcoholics Anonymous (AA)

Support group described as inexpensive cognitive-behavioral support; participation depends on willingness.

Acamprosate

Helps normalize glutamate activity elevated during alcohol withdrawal; described as a partial/weak agonist.

Naltrexone

Opioid antagonist that blocks the high/reward experienced from alcohol.

Disulfiram

Inhibits acetaldehyde dehydrogenase.

How does disulfiram discourage alcohol consumption?

It causes toxic acetaldehyde to accumulate, making the person very ill after drinking.

Acute vs. long-term alcohol medications

Acute: benzodiazepines. Long-term: acamprosate, naltrexone, disulfiram.