formic acid
Summary
Formic acid is the toxic metabolite of methanol oxidation responsible for methanol's severe toxicity including metabolic acidosis, blindness, and death. Inhibits mitochondrial cytochrome c oxidase.
Detail
Methanol is oxidized hepatically: methanol -> formaldehyde -> formic acid. Formic acid inhibits Complex IV, impairing aerobic metabolism. It causes selective toxicity to the optic nerve/retina, resulting in permanent blindness. Systemic effects include severe high anion gap metabolic acidosis, CNS depression, and cardiovascular collapse. Treatment: ethanol or fomepizole (inhibit alcohol dehydrogenase), hemodialysis, and supplemental folate (cofactor for formic acid metabolism).
Sources
- First Aid for the USMLE Step 1
- Goldfrank's Toxicologic Emergencies
- Harrison's Principles of Internal Medicine
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