L13 Alcohol

Page 1: Title

  • Pittsburgh Named "Drunkest City In Pennsylvania" by Chadd Balbi, November 27, 2023.

Page 2: Objectives

  • Describe alcohol and discuss how it is made.

  • Describe the pharmacokinetics of alcohol, including bioavailability.

  • List the behavioral effects at different blood alcohol concentrations (BAC).

  • Describe the metabolism of alcohol.

  • Explain the pharmacodynamics and mechanism of action for alcohol.

  • Describe alcohol-induced brain damage.

  • Discuss tolerance development in chronic alcohol use.

  • Explain features of fetal alcohol syndrome.

  • Discuss causes and treatments for Alcohol Use Disorder.

Page 3: Types of Alcohol

  • Ethanol (Ethyl Alcohol): The form of alcohol in drinks.

  • Methanol (Methyl Alcohol): Toxic alcohol.

  • Isopropanol (Isopropyl Alcohol): Toxic alcohol.

  • Ethanol is the only safe alcohol for consumption.

Page 4: Alcohol Production

  • Yeast fermentation breaks down sugar into carbon dioxide, ethanol, and heat.

  • Alcohol contains calories but provides no nutritional value.

  • Heavy drinkers may face nutritional deficiencies, especially from chronic usage.

Page 5: Pharmacokinetics of Alcohol

  • Determines bioavailability.

  • Ethanol is a small, water-soluble molecule, not very lipid soluble.

  • Absorbs easily from the gastrointestinal tract, diffusing throughout body tissues, including brain.

  • Behavioral effects of alcohol measured by BAC; not just amount ingested.

Page 6: Blood Alcohol Concentration (BAC)

  • Behavioral effects of ethanol depend on BAC, not just amount consumed.

  • Equivalent BAC increases from various drinks:

    • 12-oz beer, 5-oz wine, 1.5 oz spirits, and 12-oz wine cooler all raise BAC similarly.

Page 7: BAC Effects

  • 0.02 - 0.04%: Lightheadedness, minor impairment in judgment.

  • 0.05 - 0.07%: Relaxation and euphoria with impaired reasoning and memory.

  • 0.08 - 0.10%: Legally impaired; significant function impairments.

  • 0.11 - 0.15%: Depressive symptoms become pronounced, gross motor impairment.

  • 0.16 - 0.19%: Severe impairment, disorientation.

  • 0.20 - 0.24%: Stupor, possible blackout.

  • 0.25 - 0.30%: Severely impaired, dangers of accidents.

  • 0.31% and higher: Risk of coma, acute alcohol poisoning.

Page 8: Alcohol Pharmacokinetics

  • 95% of ingested alcohol metabolized by the liver at a constant rate of 1-1.5 ounces/hour.

  • 5% of alcohol is excreted via the lungs, measurable through Breathalyzer tests.

Page 9: Metabolism of Alcohol (Part 1)

  • Alcohol oxidized primarily in the liver by enzymes such as alcohol dehydrogenase and ALDH.

Page 10: Metabolism of Alcohol (Part 2)

  • Genetic variations in ALDH affect individual responses to alcohol, explaining significant variations in effects and metabolism amongst people.

Page 11: Alcohol Pharmacodynamics

  • Ethanol acts as a "dirty drug," affecting various neurotransmitter systems:

    • GABA: GABAA agonist, enhances inhibition.

    • Glutamate: Antagonist, involved in excitatory neurotransmission.

    • Dopamine: Increases transmission in limbic system, contributing to reward.

    • Opioids: Enhances endogenous opioid release, also a rewarding effect.

Page 12: Alcohol Mechanisms of Action

  • Glutamate: Acute effects reduce NMDA receptor activity and release, impacting memory and excitability.

  • Withdrawal increases glutamate release, linked to seizures and neuronal death.

Page 13: GABA Mechanism of Action

  • Alcohol enhances GABA effects. Repeated exposure leads to decreased GABA function, affecting tolerance and withdrawal.

Page 14: Dopamine and Alcohol Effects

  • Ethanol increases dopamine release via inhibition of GABA neurons, contributing to reinforcing effects of alcohol consumption.

Page 15: Opioid System Mechanisms

  • Alcohol enhances the release of endorphins, reinforcing consumption.

  • Blocking opioid receptors curtails self-administration of alcohol; variations observed in individuals with differing opioid receptor levels.

Page 16: Dopamine Turnover and Withdrawal

  • Chronic use impacts the firing rate of mesolimbic neurons, reducing DA release during withdrawal in rodents.

Page 17: Neurotransmitter Roles

Neurotransmitter

Acute Effects

Chronic Effects

Behavioral Effects

Glutamate

Antagonism

Up-regulation

Memory loss

GABA

Enhanced

Decrease

Sedation, anxiety

Dopamine

Increase

Reduced firing

Reinforcement

Opioids

Increase

Decrease

Dysphoria

Page 18: Brain Areas Affected by Alcohol

  • Amygdala: Responsible for stress and emotional responses.

  • Prefrontal Cortex: Plays a role in judgment and decision-making.

  • Hypothalamus & Pituitary: Affect sexual desire and performance, as well as temperature regulation.

Page 19: Development of Alcohol Use Disorder

  • Influencing factors include environment, genetics, stressors, and family history.

Page 20: Physical Dependence and Withdrawal

  • Chronic use leads to physical dependence; symptoms of withdrawal are influenced by usage duration and amount.

  • Withdrawal symptoms include tremors, anxiety, and sweating; severe cases may lead to delirium tremens (DTs).

Page 21: Alcohol Tolerance

  • Effects vary depending on whether blood levels are rising or falling, potentially leading to impaired driving.

Page 22: Alcoholism and Metabolic Tolerance

  • Displays differences in blood levels before and after a 7-day drinking period.

Page 23: Alcoholism: Withdrawal Symptoms

  • Symptoms include tremors, anxiety, and severe conditions like DTs, showcasing life-threatening episodes and hallucinations.

Page 24: Selected Neurotransmitter Roles (Repeated Info)

Neurotransmitter

Summary

Glutamate

Receptor antagonism and memory loss.

GABA

Enhances GABA- induced Cl-influx.

Dopamine

Involved in reinforcement behaviors.

Opioids

Increase in endogenous opioid levels.

Page 25: Effects of Long-Term Alcohol Use

  • Brain Damage: Direct damage, liver functional insufficiency, inadequate nutrition (thiamine deficiency).

  • Thiamine is essential for brain metabolism; absence leads to neuron death.

Page 26: Effects of Long-Term Alcohol Use: Korsakoff’s Syndrome

  • Characterized by memory function loss and confabulation.

  • Damage associated with thalamus from vitamin B1 deficiency; thiamine treatment halts degeneration but does not reverse damage.

Page 27: Effects of Long-Term Alcohol Use: Liver Disease

  • Fatty Liver: Accumulation of triglycerides.

  • Alcoholic Hepatitis: Liver damage from acetaldehyde accumulation.

  • Cirrhosis: Liver cell death leading to scar formation and blood supply restriction.

  • Coffee has protective benefits against liver diseases.

Page 28: Fetal Alcohol Syndrome (FAS)

  • Alcohol crosses the placental barrier, leading to similar BAC levels in fetus.

  • Symptoms of FAS include:

    • Intellectual disability and behavioral issues.

    • Physical abnormalities such as craniofacial malformations.

    • Other defects in cardiac and kidney development.

Page 29: Treatment of Alcohol Use Disorder - Detoxification

  • Withdrawal symptoms are intense and hazardous; BZDs like chlordiazepoxide or diazepam are used to mitigate symptoms.

  • Other modalities: individual/group therapy, residential treatment, self-help groups such as AA, community reinforcement, and cognitive behavioral therapy.

Page 30: Pharmacotherapeutic Treatments for Alcoholism

  • Two primary strategies:

    1. Reducing withdrawal symptoms using alternatives like benzodiazepines in detox programs.

    2. Reducing positive reinforcement (e.g. through AA support).

Page 31: Interventions to Reduce Positive Reinforcement

  • Disulfiram (Antabuse): Inhibits ALDH, causing unpleasant reactions to alcohol.

  • Naltrexone (Vivitrol): Opioid receptor antagonist that decreases alcohol cravings and consumption.

Page 32: Emerging Treatment Options for Rehabilitation

  • New treatments examine CRF1 antagonists, glucocorticoid receptor antagonists, and NMDA receptor antagonists (e.g., ketamine) to counteract hyperexcitability in withdrawal.

Page 33: Research on Craving and Drinking Behavior

  • Study showed glucocorticoid receptor antagonism reduced alcohol-cued cravings and drinking.