Alcohol Pharmacokinetics and Pharmacodynamics

Alcohol Pharmacokinetics

• Absorption: Alcohol readily diffuses across membranes, quickly entering the bloodstream from the gastrointestinal tract.
• Distribution: Easily crosses the blood-brain barrier.
• Metabolism (Biotransformation):
  • Approximately 15% metabolized by gastric alcohol dehydrogenase (in the liver).
  • Women tend to have less gastric alcohol dehydrogenase than men.
  • The average person metabolizes about 10 mL of 100 proof alcohol per hour (zero-order metabolism).
  • The metabolite acetaldehyde is responsible for the unpleasant feelings after drinking.
  • Alcohol is broken down into acetaldehyde by alcohol dehydrogenase.
  • Acetaldehyde is further broken down into acetic acid by aldehyde dehydrogenase.
• Excretion: About 5% is excreted through the lungs.

Alcohol Pharmacodynamics

• Glutamate: Alcohol suppresses NMDA receptor function and reduces glutamate release.
  • Chronic alcohol consumption increases NMDA receptors.
• GABA: Alcohol is a GABA agonist, increasing chloride influx.
  • Chronic alcohol consumption reduces chloride influx.
• Opioids: Alcohol induces opioid release, leading to pain relief, sleepiness, and increased intestinal motility.
• Cannabinoid System: Alcohol stimulates the production of anandamide, an endogenous cannabinoid similar to THC ("dirty drug" label).

Alcohol Tolerance

• Acute: Occurs with a single exposure.
• Metabolic: Liver alcohol dehydrogenase increases.
• Pharmacodynamic: NMDA receptor activity increases; GABA chloride influx decreases.
• Behavioral: Leads to alcoholism (alcohol use disorder).

Alcohol Use Disorder (AUD) Pharmacotherapy

• Goals: Prevent/treat withdrawal seizures, prevent relapse, and treat comorbid conditions.
• Prevent/Treat Withdrawal Seizures: Use long-acting benzodiazepines (e.g., diazepam) or anticonvulsants (e.g., lamotrigine, topiramate).
• Prevent Relapse: Disulfiram (Antabuse) or calcium carbimide (Temposil) inhibit aldehyde dehydrogenase, increasing the unpleasant acetaldehyde effects, (low patient compliance).
  • Naltrexone (ReVia, Trexan), a mu opioid antagonist, is used for relapse prevention (better than placebo; injection possibly more effective).
• Treat Comorbid Conditions: Depression and PTSD (often difficult to treat).

Binge Drinking

• Definition (NIAAA): Drinking enough in two hours to reach a BAC of 0.08 or higher.
• Effects: Increased inflammation, oxidative stress, excitotoxicity, and HPA axis activity. Reduced trophic support and neurogenesis .
• Consequences: White matter tracks shrink due to increased inflammation and oxidative stress.
• Frequency: A single binge weekly can be neurologically harmful. Often occurs during college years.
• Correlation: Women and binge drinking show a correlation.

Explore the intricate processes of alcohol absorption, distribution, metabolism, and excretion in this quiz. Delve into the pharmacodynamic effects of alcohol, such as its impact on NMDA receptor function. Test your knowledge on how gender differences affect alcohol metabolism and the pathways involved.