Fomepizole (4-Methylpyrazole)
Definition
A specific competitive inhibitor of alcohol dehydrogenase (Ki approximately 0.1 µM), used as the preferred antidote for methanol poisoning in high-resource settings. Blocks methanol conversion to formaldehyde, allowing renal and respiratory excretion of unmetabolised methanol.
- Mechanism
- Competitive inhibitor of alcohol dehydrogenase
- Approximate Ki
- About 0.1 micromolar
- Indication
- Preferred antidote for methanol poisoning in high-resource settings
- Effect
- Blocks conversion to formaldehyde, permitting renal/respiratory excretion
Common questions
What does the very low Ki value of fomepizole indicate about its clinical advantage over ethanol?+
A low Ki reflects extremely high binding affinity for alcohol dehydrogenase, meaning fomepizole blocks the enzyme effectively at low, stable doses without needing the continuous blood-level monitoring that ethanol therapy requires to stay within its narrower effective range.
Why is fomepizole described as preferred specifically in high-resource settings rather than universally?+
It requires the drug itself to be stocked and is considerably more expensive than ethanol, so its use as first-line therapy depends on hospital resources and drug availability, which is why lower-resource settings often rely on ethanol as the practical alternative despite it needing closer monitoring.
Once methanol conversion is blocked, how is the unmetabolised methanol actually eliminated from the body?+
With the toxic metabolic pathway blocked, unchanged methanol is cleared through the kidneys in urine and through the lungs by exhalation, a much slower but far less toxic route than continued conversion to formic acid, and severe cases may still need haemodialysis to speed clearance.
Related terms
- Alcohol Dehydrogenase (ADH)
- The hepatic enzyme (isoforms ADH1A, ADH1B, ADH1C) that catalyses the first oxidation step of both ethanol (to acetaldehyde) and methanol (to formaldehyde)...
- Anion-Gap Metabolic Acidosis
- The metabolic acid-base disorder produced by accumulating formate in methanol poisoning. The anion gap (Na+ - [Cl- + HCO3-], normal 8-12 mEq/L)...
- Congener Fingerprinting
- The use of the full volatile congener profile (fusel alcohols, acetaldehyde, ethyl acetate, pyridine, MIBK) in illicit liquor samples to establish batch...
- Formate (Formic Acid)
- The terminal toxic metabolite of methanol oxidation (HCOO-, pKa 3.7). Formate inhibits cytochrome c oxidase (mitochondrial complex IV), causing optic nerve and...
- FSSAI Methanol Limit
- Under India's Food Safety and Standards (Alcoholic Beverages) Regulations 2018, the maximum methanol content permitted in legally produced and sold spirits is...
- Haemodialysis in Methanol Poisoning
- The most efficient treatment for removing both methanol and formate from circulation and correcting severe metabolic acidosis. The EXTRIP workgroup (US) and...
- Latency Period
- The 12-24 hour window between methanol ingestion and onset of severe symptoms (visual disturbance, metabolic acidosis), during which the patient may appear...
- Pyridine
- An aromatic nitrogen heterocycle used as a secondary denaturant in Indian denatured spirit formulations (at 1-2% v/v). Its presence in a headspace...
- Vitreous Humour
- The gel-filled interior of the eye, anatomically isolated from hepatic and gastric post-mortem redistribution sources. In forensic toxicology of hooch deaths, vitreous...