Alcohol use disorder

Alcohol metabolism

Key Point

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

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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

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Naltrexone and acamprosate are preferred.
- Naltrexone: central μ-opioid receptor antagonist
- Acamprosate: may modulate central glutamate receptors
Both medications reduce cravings and can be used for patients who:
- Continue to drink alcohol
- Use other substances recreationally

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

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.

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

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^-)

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)