9. Pharmacology of Alcohols - Pharm

• Alcohol - gastric and liver first pass metabolism by alcohol dehydrogenase (ADH)
• In CNS - alcohol is a depressant

  • enhance GABA stimulated influx of chloride
  • inhibit NMDA
  • inhibit L type Ca2+ channel
• Alcohol cause peripheral vasodilation

  • depress vasomotor center
  • relaxation of vascular smooth muscle by acetaldehyde
  • produce feeling of warmth but body temp actually falls - hypothermia
• Ethanol effect on gastric mucosa

  • small dose - improves appetite
  • large dose - gastric irritation
  • injury to mucosa
• In chronic alcohols -

  • stomach - chronic gastritis leads to anemia and protein malnutrition
• alcohol cause vomiting by

  • activation of 5HT3 receptor
• effect of ethanol on reproduction/endocrine

  • testicular atrophy
  • women - amenorrhea and miscarriage
• alcohol - cause gout = hyperuricemia
• the French paradox - daily intake of alcohol

  • increase HDL - prevent CAD & atherosclerosis
• Alcohol dependence syndrome - alternation to CNS neurotransmission

  • acute - blockage of NMDA
  • chronic
  • increase NMDA
  • increase L type Ca2+ channel
  • decrease GABAa
• alcohol and drug interaction

  • due to cross tolerance BZD and general anesthetics require higher dose
• avoid alcohol and BZD cause respiratory depression
• 1st gen antihistamine + alcohol = avoid due to increase sedating effects
• Don't use acetaminophen with alcohol

  • ethanol induce enzyme CYP2E1 - acetaminophen metabolizes into NAPQI (toxic) to liver
• treat acute alcoholism

  • treat hypoglycemia + ketoacidosis by glucose
  • thiamine given before glucose
• Chronic alcoholism cause

  • deficiency of thiamine (B1)
  • give thiamine to prevent wernicke korsakoff syndrome
• Alcohol withdrawal syndrome - Delirium symptom

  • use lorazepam
  • to treat agitation and hallucination - use haloperidol or olanzapine
• To reduce withdrawal syndrome + detoxification

  • use long acting BZD such as chlordia or diazepam
  • then gradually reduce the dose (tapering)
• Disulfiram - use for aversion therapy or Antabuse

  • MOA
  • inhibit aldehyde dehydrogenase (ALDH) and block oxidation of acetaldehyde to acetic acid
  • increase acetaldehyde - facial flushing
• Disulfiram - cause extreme discomfort in pts who drinks alcohol

  • do not use with medication containing alcohol
• Do not combine disulfiram + naltrexone = hepatotoxic
• naltrexone use to reduce rate and craving for alcohol

  • opioid antagonist
• acamprosate

  • weak NMDA antagonist + GABAa receptor activator
  • use to decrease craving for alcohol
• ethylene glycol (antifreeze) - treatment

  • fomepizole - inhibit alcohol dehydrogenase
  • intravenous ethyl alcohol
• methanol poisoning (wood alcohol) causes

  • blindness - like being in snow storm
  • form metabolite formic acid - causing severe anion gap metabolic acidosis
• Methanol poisoning - treatment

  • correct acidosis with IV NaHCO3
  • inhibit methanol metabolism
  • fomepizole - inhibitor of ADH
  • IV ethanol to complete with methanol
  • leucovorin - enhance clearance of formate
• ethylene glycol - toxic metabolites

  • glycolic acid
  • oxalic acid