A 24-year-old male is brought unconscious after ingesting paint thinner. His blood methanol level is 40 mg/dL and he has metabolic acidosis with high anion gap. Which biochemical step is blocked by fomepizole to prevent methanol toxicity?

• A Aldehyde dehydrogenase — prevents conversion of formaldehyde to formic acid
• B Formate dehydrogenase — prevents conversion of formate to CO₂
• C Catalase — prevents alternative pathway of methanol oxidation
• D Alcohol dehydrogenase — prevents conversion of methanol to formaldehyde ✓

Explanation

Methanol itself is non-toxic; its metabolites are toxic. Alcohol dehydrogenase (ADH) converts methanol → formaldehyde (toxic), which is then converted to formate by aldehyde dehydrogenase. Formate accumulates, inhibits cytochrome oxidase, and causes optic nerve toxicity and metabolic acidosis. Fomepizole is a competitive inhibitor of ADH, blocking the first and rate-limiting step. Ethanol works by the same mechanism but fomepizole is preferred due to predictable pharmacokinetics.

Reference: The Essentials of Forensic Medicine and Toxicology (Narayan Reddy), 34th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.