Alcohol Awareness Quiz

Pittsburgh Named "Drunkest City in Pennsylvania"

• Pittsburgh is considered the "Drunkest City in Pennsylvania" based on data
• The date of this declaration is November 27, 2023

Objectives

• Describe alcohol and its production
• Detail the pharmacokinetics and bioavailability of alcohol
• List the behavioral effects based on different blood alcohol concentrations (BAC)
• Describe alcohol's metabolism
• Explain the pharmacodynamics and mechanism of action for alcohol
• Describe alcohol-induced brain damage
• Describe tolerance development (chronic alcohol use effects)
• Detail the characteristics of fetal alcohol syndrome
• Discuss the causes and treatments for Alcohol Use Disorder

What is an Alcohol?

• Ethanol (ethyl alcohol) is the type of alcohol found in drinks
• Methanol (methyl alcohol) and isopropyl alcohol are other types, but are toxic

How is Alcohol Made?

• Yeasts break down sugar to produce alcohol and carbon dioxide
• Alcohol has calories but no nutritional value; heavy drinkers can suffer malnutrition

Pharmacokinetics of Alcohol

• Ethanol is a small molecule that mixes readily with water, not very lipid soluble
• Easily absorbed from the GI tract and diffuses throughout tissues, including the brain
• Behavioral effects are linked to BAC rather than amount ingested

Blood Alcohol Concentration (BAC)

• Many factors affect blood ethanol levels, so behavioral effects are measured by BAC, not the amount ingested
• A 12-oz can of beer, 5-oz glass of wine, 1.5-oz spirit cocktail, or 12-oz wine cooler all have same BAC increase

Blood Alcohol Concentration (BAC) - Effects Experienced

• BAC levels are associated with specific effects
• .02-.04%: Lightheadedness, relaxation, warmth, minor judgment impairment
• .05-.07%: Buzzed, relaxation, euphoria, decreased inhibition, minor reasoning and memory impairment, exaggerated emotions.
• .08-.10%: Legally impaired, euphoria, fatigue, balance, speech, vision, reaction time, hearing, judgment, and self-control impaired
• .11-.15%: Impaired, depressive effects (anxiety, depression, unease) are more apparent. Gross motor impairment, judgment and perception severely impaired
• .16-.19%: Very drunk, state of depression, nausea, disorientation, dizziness, and significant motor impairment. Judgment worsened
• .20-.24%: Dazed and confused, gross disorientation, nausea, vomiting, significant motor impairment, need for assistance to walk or stand, and blackouts are likely.
• .25-.30%: Stupor, all mental, physical, and sensory functions severely impaired, high probability of accidents, impaired comprehension, may pass out suddenly
• .31% and up: Coma, surgical amnesia, acute alcohol poisoning, and death from respiratory arrest is very likely

Alcohol: Pharmacokinetics

• Blood alcohol levels vary based on oral dose and if taken with food
• Different types of alcohol, different bioavailability

Alcohol Metabolism (Part 1)

• About 95% of alcohol is metabolized by the liver at a consistent rate.
• Remaining alcohol is excreted through the lungs (measured by breathalyzer).
• Alcohol is oxidized by alcohol dehydrogenase and aldehyde dehydrogenase. This process creates CO2, water, and energy.

Alcohol Metabolism (Part 2)

• Genetic differences in aldehyde dehydrogenase activity influence alcohol metabolism rates
• Increased levels of acetaldehyde and reduced activity of ALDH can cause negative side effects like flushing, nausea, headache, or increased heart rate

Pharmacodynamics of Alcohol

• Ethanol/alcohol is considered a "dirty drug" with diverse actions, affecting membrane fluidity and ion channels
• Acts as an agonist at GABA receptors (enhances GABA release)
  • Affects different GABA receptors, impacting reinforcing effects
• Acts as an antagonist at glutamate receptors (reduces glutamate release).
• Repeated use may result in glutamate receptor upregulation
• Increases dopamine transmission in the limbic system, leading to rewarding (reinforcing) effects
• Increases endogenous opioid synthesis and release, potentially contributing to reinforcement

Alcohol: Mechanisms of Action

• Ethanol increases dopamine release in the nucleus accumbens (NAc). GABA inhibition in VTA plays a role.
• Affects opioid systems contributing to reinforcement and potentially enhancing release from the pituitary gland
• Blocking opioid receptors reduces alcohol-seeking behavior in animal models
• Chronic alcohol use may diminish available endogenous opioids

Alcohol Withdrawal (Dopamine Turnover)

• Chronic alcohol use in rodents affects mesolimbic neurons' firing rates and reduces dopamine release in the nucleus accumbens (NAcc)

Role of Selected Neurotransmitters in Beer-Related Disorders

• Neurotransmitters play a role in the various effects and behaviors associated with alcohol, from acute and chronic cellular impacts to behavioral outcomes

Brain Areas Affected by Alcohol

• Prefrontal cortex (judgment, decision-making, motivation), glutamate, GABA, dopamine impacted
• Amygdala (stress responses, emotional responses) affected
• Hypothalamus and Pituitary (sexual desire and performance, temperature regulation) impacted
• Hippocampus (learning and memory affected, seizures, depression) impacted
• Cerebellum (motor coordination affected)

Stages in the Development of Alcohol Use Disorder

• Social drinking
• Problem/abusive drinking
• Dependence
• Excessive and uncontrollable drinking
• Abstinence
• Acute/protracted withdrawal symptoms
• Relapse

Chronic Alcohol Use Leads to Physical Dependence

• Physical dependence severity depends on alcohol use amount and duration
• Cross-dependence with other sedative-hypnotic drugs observed
• Hangover as a potential symptom of withdrawal or acute toxicity
• Withdrawal symptoms can range from tremor and anxiety to high blood pressure, rapid heart rate, sweating, rapid breathing, nausea, vomiting; severe cases may include delirium tremens (DTs)

Tolerance to Alcohol (Acute Tolerance)

• Effects of a single alcohol exposure are stronger while BAC rises and become weaker as BAC falls. This can lead to mistakes like driving when intoxicated.

Alcoholism: Metabolic Tolerance

• Tolerance to alcohol develops over a period of time, including metabolic tolerance
• Blood alcohol levels before and after 7 days of alcohol consumption are different
• Shows that the body adapts to alcohol use

Alcoholism: Withdrawal Symptoms

• Withdrawal symptoms, including tremor (the shakes), anxiety, high blood pressure, rapid heart rate, sweating, rapid breathing, nausea, vomiting, will be apparent when the body adjusts from alcohol use

Effects of Long-Term Heavy Alcohol Use: Brain Damage

• Direct damage from alcohol
• Elevated acetaldehyde
• Insufficient liver function
• Inadequate nutrition, especially thiamine (critical for brain glucose metabolism)

Effects of Long-Term Heavy Alcohol Use: Korsakoff's Syndrome

• Progressive permanent loss of memory, often accompanied by confabulation
• Anterograde amnesia: inability to form new memories
• Retrograde amnesia: difficulty retrieving past memories, especially newly formed ones.
• Caused by damage to the thalamus from chronic thiamine(Vitamin B1) deficiency
• Thiamine treatment can slow degeneration but doesn't reverse it

Effects of Long-Term Heavy Alcohol Use: Liver Disease

• Fatty liver: triglycerides accumulate in liver cells, leading to fat build-up in the liver
• Alcoholic hepatitis: liver cell damage from acetaldehyde accumulation
• Alcoholic cirrhosis: liver cell death, which triggers scar tissue and blocks blood supply
• Eventually, the liver becomes significantly damaged

Effects of Long-Term Heavy Alcohol Use: Fetal Alcohol Syndrome (FAS)

• Alcohol readily crosses the placental barrier, affecting the fetus
• Damages fetal development, leading to FAS
• Symptoms include intellectual disability, cognitive/behavioral delays, low birthweight, craniofacial defects, and other physical abnormalities

Treatment of Alcohol Use Disorder

• Detoxification: withdrawal symptom treatment, often with benzodiazepines like chlordiazepoxide (Librium) and diazepam (Valium)
• Psychosocial rehabilitation programs (individual/group therapy, residential settings, self-help groups like AA, community reinforcement approach (CRA), cognitive behavior therapy)
• Pharmacotherapeutic treatments (reducing withdrawal symptoms like with benzodiazepines, reducing positive reinforcement like with disulfiram or naltrexone)

Multiple Treatment Options for Rehabilitation

• CRF antagonists
• Glucocorticoid receptor (GR) antagonists
• Ketamine

Next Time: Exam Review

Test your knowledge about alcohol, its effects, and the concepts surrounding its use. This quiz covers topics such as alcohol production, pharmacokinetics, and the impact on behavior and health. Learn about Alcohol Use Disorder and related conditions.