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Methanol poisoning
A man who drank illicit liquor has blurred vision progressing to blindness, with a severe high anion gap metabolic acidosis. Which metabolite is responsible, why does it damage the eye specifically, and what is the antidote?
- A. Glycolic acid; it damages the retinal pigment epithelium; pyridoxine
- B. Oxalic acid; it crystallises in the retina; calcium gluconate
- C. Acetaldehyde; it binds retinal proteins; disulfiram
- correctD. Formic acid; it inhibits cytochrome c oxidase in the optic nerve; fomepizole or ethanol
Explanation
Key fact
The alcohol is not the poison; its metabolite is. Formic acid poisons mitochondrial respiration, and the optic nerve is most vulnerable.
Formic acid, inhibiting cytochrome c oxidase, treated with fomepizole or ethanol. Both work by blocking alcohol dehydrogenase.
Why
Alcohol dehydrogenase converts methanol to formaldehyde, then to formic acid.
Formate inhibits cytochrome c oxidase, blocking oxidative phosphorylation.
The optic nerve has a high metabolic demand and is affected first.
The same block generates lactate, adding to the anion gap.
Fomepizole inhibits alcohol dehydrogenase, so the parent alcohol is excreted unchanged.
Blocking the enzyme, not the poison
Why not the others
- A. Glycolic acid; it damages the retinal pigment epithelium; pyridoxine — is an ethylene glycol metabolite; pyridoxine and thiamine are adjuncts there, not antidotes here.
- B. Oxalic acid; it crystallises in the retina; calcium gluconate — belongs to ethylene glycol, and its crystals form in the kidney, not the retina.
- C. Acetaldehyde; it binds retinal proteins; disulfiram — is the metabolite of ordinary ethanol, and disulfiram causes rather than treats its accumulation.
Remember
Methanol blinds through formate; ethylene glycol kills kidneys through oxalate. One antidote blocks both.
Go deeper
Ethanol works as an antidote because alcohol dehydrogenase prefers it, but it is harder to titrate and adds sedation - fomepizole is preferred where available.
Haemodialysis removes both the parent alcohol and its metabolites, and is used for severe acidosis, visual symptoms or renal failure.
The osmolar gap is high early, before metabolism, and the anion gap rises later as the acid accumulates - the two gaps move in sequence.
Reddy KSN, Murty OP. The Essentials of Forensic Medicine and Toxicology, 36th ed. (Jaypee, 2025); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (McGraw Hill, 2023).