alcohol

ALCOHOL

Introduction

  • Chapter 10 on Alcohol

  • Important announcements: Please turn off cell phones and sign the attendance sheet.

THINGS YOU WILL LEARN TODAY

  • Understand how beer contributed to the construction of the Egyptian pyramids.

  • Learn the importance of eating before a night of drinking.

  • Explore how alcohol can lead to blackouts.

ALCOHOL: Definition and Effects

  • Alcohol is produced by the fermentation of sugars by yeasts.

    • Major psychoactive compound: Ethyl alcohol (ethanol).

    • Contains calories but holds no nutritional value.

  • Effects of alcohol:

    • Low Dose (Stimulant-like Effects):

    • Euphoria

    • Disinhibition

    • Decreased anxiety

    • Relaxation

    • Talkativeness

    • Poor judgment

    • High Dose (Depressant Effects):

    • Impaired motor function

    • Slowed cognition

    • Unconsciousness

    • Potentially fatal (death).

HISTORY OF ALCOHOL

  • 11000 BCE (Israel): First evidence of beer.

  • 8000 BCE (China): Mead brewed from fermented honey.

  • 3700 BCE (Egypt): Production of hearty beer known as "hek."

  • 1700 BCE (Babylonia): Introduction of wine.

  • 1600s (Dutch): Emergence of gin; onset of serious misuse in Europe.

  • 1920-1933: Prohibition era in the United States.

ALCOHOL PHARMACOKINETICS

  • Ethanol mixes easily with water but is not lipid soluble.

  • Easily absorbed from the gastrointestinal (GI) tract and penetrates most tissues, including the brain.

  • Blood Alcohol Concentration (BAC) describes behavioral effects of alcohol.

  • Absorption Details:

    • Majority absorbed from the small intestine (90%).

    • Presence of food in the stomach delays movement into the small intestine and thus delays absorption.

    • The pyloric sphincter regulates the movement of material from the stomach to the intestine.

  • Differences in absorption between sexes:

    • Women generally experience faster absorption of alcohol relative to men due to

    • Reduced gastric metabolism (less alcohol dehydrogenase).

    • Smaller average body size.

    • Higher fat-to-water ratio.

ALCOHOL METABOLISM

  • General Metabolism:

    • 95% of alcohol is metabolized by the liver at a constant rate of approximately 1 to 1.5 ounces per hour.

    • 5% is excreted through the lungs.

    • Alcohol is oxidized to acetaldehyde by alcohol dehydrogenase, which is toxic, and then converted to acetic acid by aldehyde dehydrogenase (ALDH).

  • Genetic Variants in ALDH:

    • 10% of Asian individuals possess homozygous alleles resulting in inactive forms of the enzyme.

    • 40% have heterozygous alleles.

  • Enzymatic Action:

    • Other enzymes in the cytochrome P450 family also convert alcohol to acetaldehyde and metabolize many other drugs.

    • Consumption of alcohol along with other drugs can lead to competition for the same enzyme, potentially resulting in dangerously high levels of these other drugs.

ALCOHOL TOLERANCE

  • Types of Tolerance:

    • Metabolic Tolerance Induction:

    • Occurs when alcohol is consumed regularly, leading to an increase in liver enzyme levels.

    • Pharmacodynamic Tolerance:

    • Neurons adapt to the continuous presence of alcohol, leading to compensatory changes in cell function.

    • Behavioral Tolerance:

    • Practicing alcohol-influenced behaviors leads to adjustments and compensations in those behaviors.

HANGOVER

  • Debate exists regarding whether a hangover indicates withdrawal or toxicity.

  • Possible causes include:

    • Residual acetaldehyde in the system.

    • Gastric irritation.

    • Rebound drop in blood sugar.

    • Fluid loss and sleep deprivation.

    • Toxic effects from fermentation by-products (congeners).

  • Symptoms may include:

    • Nausea

    • Vomiting

    • Headaches

    • Dehydration

    • Sensitivity to light

    • Fatigue

    • Mild cognitive dysfunction

    • Irritability

    • Depression.

ALCOHOL WITHDRAWAL

  • Occurs after repeated heavy use over a span of months or years.

  • Withdrawal symptoms can manifest sharply just a few hours after the cessation of alcohol consumption, lasting up to 2-4 days. Symptoms may include:

    • Tremors

    • Intense anxiety

    • High blood pressure

    • Rapid heart rate

    • Vomiting.

  • Delirium Tremens (DTs):

    • Symptoms include irritability, headaches, agitation, confusion.

    • The most extreme symptoms can be life-threatening, including convulsions and seizures.

ALCOHOL EFFECTS

  • Alcohol impacts the brain by relaxing it, reducing anxiety, and impairing judgement and memory.

  • Common consequences of high alcohol consumption include:

    • Increased risk of car accidents, violent crimes, and aggression.

    • Potential for alcohol poisoning, coma, and death due to respiratory depression.

    • Specific Blood Alcohol Concentration (BAC) effects include:

    • BAC of approximately 0.15% can lead to vomiting.

    • BAC of approximately 0.35% can lead to unconsciousness.

    • BAC of approximately 0.45% is lethal.

ALCOHOL EFFECTS: Long-term Impact

  • Years of heavy alcohol use can lead to brain damage, exacerbated by poor diets (specifically lack of thiamine).

  • Korsakoff Syndrome:

    • Results from thalamic nuclei atrophy and leads to severe anterograde amnesia and confabulation.

  • Other physical brain impacts include:

    • Enlargement of ventricles,

    • Decreased overall brain mass,

    • Loss of cerebellar cells.

ALCOHOL EFFECTS: Health-Related

  • Low to moderate alcohol use may decrease the likelihood of developing dementia, dilates blood vessels, and potentially improve cognition in older adults.

  • Lowering risk of heart disease: alcohol raises the level of “good” cholesterol while reducing levels of “bad” cholesterol.

  • Conversely, there is also an increased risk of cancer.

  • Data is currently contrasting on the beneficial versus detrimental effects of alcohol consumption.

ALCOHOL EFFECTS: Physiological Reactions

  • Alcohol has a diuretic effect, contributing to fluid loss and increased dilution in urine. It reduces the secretion of antidiuretic hormone.

  • While it may increase sexual arousal, it can also decrease sexual performance.

  • Alcohol consumption can boost appetite and aid digestion.

  • Alcohol Use Disorder (AUD):

    • AUD is associated with severe liver damage including fatty liver, alcohol-induced hepatitis, and cirrhosis.

  • Fetal Alcohol Syndrome (FAS):

    • Occurs when alcohol crosses the placental barrier, leading to intellectual disabilities, developmental delays, low birth weight, neurological problems, and malformations of the head/facial structure.

ALCOHOL'S ACTION ON NEUROTRANSMITTERS

  • Alcohol acts on multiple neurotransmitter systems by:

    • Nonspecifically altering cell membrane lipids leading to increased fluidity, affecting membrane protein interactions.

  • Specific Actions:

    • Influences ligand-gated channels and alters second-messenger systems.

Glutamate

  • Alcohol reduces the effect of glutamate on NMDA receptors at approximately 0.03% BAC, which impairs learning and memory.

  • This reduction can lead to blackout mechanisms due to decreased glutamate release during acute and withdrawal phases.

  • During withdrawal, glutamate release may increase and lead to hyperexcitability and seizures, while also leading to irreversible brain damage.

GABA

  • Ethanol enhances GABA-induced chloride ion (Cl-) flux leading to hyperpolarization and stimulates GABA release, particularly affecting extrasynaptic GABAA receptors endowed with δ subunits.

  • These receptors maintain a persistent response to GABA and show heightened sensitivity to alcohol, mediating its reinforcing effects.

  • Alcohol can reduce GABAA-mediated chloride flux during AUD.

Dopamine

  • Alcohol affects the mesolimbic pathway by activating dopamine (DA) cells in the ventral tegmental area (VTA), which results in the release of dopamine in the nucleus accumbens (NAcc).

  • This pathway is critically involved in the process of positive reinforcement. During withdrawal, alcohol reduces the firing rate of dopamine cells in the VTA, leading to decreased dopamine release in the NAcc.

Opioids

  • Endorphins released from the pituitary gland due to alcohol consumption contribute to its reinforcing effects.

  • Blocking opioid receptors can reduce alcohol self-administration, while high levels of μ-opioid receptors are correlated with craving.

ALCOHOL USE DISORDER (AUD)

  • Understanding AUD:

    • AUD is challenging to define as it encompasses a cluster of problematic drinking behaviors characterized by behavioral, cognitive, and physical factors.

    • Statistics indicate that approximately 10% of Americans have issues related to alcohol use.

    • Early drinking experiences (<13 years old) are predictive of developing AUD later in life.

    • Binge drinking is defined as:

    • Men: Consuming 5 drinks in a row.

    • Women: Consuming 4 drinks in a row.

ALCOHOL USE DISORDER: RISK FACTORS

  • Psychological Factors:

    • Environmental stress

    • Family history of alcoholism

    • Anxiety, particularly if experienced early in life.

    • Increased novelty seeking and risk-taking behaviors are notable.

  • Genetic Factors:

    • Relatives of individuals with AUD face a 3-7 times greater risk of developing a similar disorder.

  • Sociocultural Factors:

    • Cultures where alcohol consumption is abstained from tend to exhibit the lowest rates of AUD.

ALCOHOL USE DISORDER: TREATMENT

  • Detoxification Process:

    • Withdrawal symptoms can be severe, necessitating treatment under medical supervision.

    • Benzodiazepines are often administered to manage withdrawal symptoms, which can escalate with subsequent episodes.

    • Seizures are included in potential symptoms to monitor.

  • Psychosocial Rehabilitation:

    • Involves cognitive behavioral therapy and self-help methods such as Alcoholics Anonymous (AA).

  • **Pharmacotherapeutic Treatment Strategies:

    • Two main strategies are utilized:**

    • Making Drinking Unpleasant:

      • Example: Disulfiram (Antabuse) inhibits ALDH, leading to adverse effects like flushing, a pounding heart, nausea, and vomiting after alcohol consumption.

    • Reducing Alcohol's Reinforcing Qualities:

      • Example: Naltrexone (Revia) is an opioid receptor antagonist that diminishes the "high" by blocking endorphin release associated with alcohol consumption.