Alcohol use disorder

Alcohol metabolism

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Key Point

Ethanol metabolism increase NADH/NAD+, which further downregulate gluconeogenesis and TCA cycle, and increase lactate.

Mnemonic

• Fomepizole: think it as Foam-epizole, which can turn the beer to a lot of foam and less liquid (dehydro).
  • Used for alcohol intoxication
• Disulfiram: diSUFFERam. It can increase acetaldehyde and make people sick and dizzy.
  • Used in alcohol use disorder, as 2nd line treatment

Treatment

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Pharmacotherapy

• Psychosocial: Alcoholics Anonymous (AA) and cognitive-behavioral therapy (CBT) are mainstays.
• Pharmacotherapy:
  • Naltrexone: Opioid antagonist; decreases cravings and the rewarding effects of alcohol. Can be given as a daily pill or monthly injection.
    • An opioid antagonist makes drinking less rewarding by blocking the pleasurable “high” at a neurochemical level, thereby reducing the motivation to drink.
  • Acamprosate (Campral): Modulates glutamate transmission. Used to maintain abstinence, particularly in those who have already stopped drinking.
  • Disulfiram (Antabuse): Inhibits aldehyde dehydrogenase, causing an accumulation of acetaldehyde if alcohol is consumed. This leads to unpleasant symptoms like nausea, vomiting, and flushing. Used as a deterrent.

Complications

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Multisystem complications

• Cytochrome P450 induction
• Vitamin deficiency
  • Vitamin B1 deficiency (thiamine deficiency): Wernicke-Korsakoff syndrome
  • Vitamin B6 deficiency: peripheral neuropathy
  • Vitamin B9 deficiency (folate deficiency): megaloblastic anemia
    • Depletion would take place over weeks
  • Vitamin B12 deficiency: subacute combined degeneration of spinal cord (funicular myelosis), megaloblastic anemia
    • Depletion would take place over years
• Electrolyte abnormalities: Hyponatremia, Hypokalemia, Hypocalcemia
  • Often caused by complications such as malnutrition, vomiting, or diarrhea

Alcohol intoxication

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Pathophysiology

• Mechanism
  • GABA-A receptor agonist → Chronic use causes downregulation of GABA-A receptors → decreased GABA-A activity when cessation
  • NMDA glutamate antagonist → chronic use causes upregulation of NMDA receptors → increased glutamate NMDA activity when cessation
• Absorption: The majority of alcohol consumed is absorbed by the proximal small intestine; only a small amount of alcohol is absorbed by the oral, esophageal, and/or gastric mucosa.

Clinical features

Altered consciousness, cognition, perception, judgment, affect, and/or behavior.

Diagnostics

• Routine laboratory studies that support the diagnosis include:
  • Elevated osmolar gap
    • The difference between the measured serum osmolarity and the calculated serum osmolarity. Normally, the calculated serum osmolarity is primarily determined by circulating levels of sodium salts (chloride and bicarbonate), glucose, and urea. An increased serum osmolar gap occurs when other solutes (e.g., ethanol, methanol, propylene glycol) are present in high enough concentrations to increase the measured osmolarity by more than 10 mOsmol/L.
  • Anion gap metabolic acidosis (e.g., ↓ pH, ↓ HCO₃^-)

Treatment

Alcohol dehydrogenase inhibitors

• Goal: to prevent the conversion of methanol or ethylene glycol to toxic metabolites (e.g., formic acid, glycolic acid, oxalic acid) by competitively inhibiting alcohol dehydrogenase
• Options
  • Fomepizole (first-line): a competitive alcohol dehydrogenase inhibitor; safer and easier to administer than ethanol
  • Ethanol (second-line)