Toxicology – Antidotes for Toxic Alcohols: Fomepizole, Ethanol & Hemodialysis

Metabolic Pathways

Methanol and ethylene glycol become dangerous mainly after they are metabolized by alcohol dehydrogenase (ADH) into toxic metabolites.

• Methanol → formaldehyde → formic acid
• Ethylene glycol → glycolaldehyde → glycolic acid → glyoxylic acid → oxalic acid
• Ethanol → acetaldehyde → acetic acid

Ethanol

Ethanol has a higher affinity for ADH than methanol or ethylene glycol. By occupying the enzyme, it slows formation of their toxic metabolites and allows more of the parent alcohol to be eliminated unchanged.

Disadvantages include:

• CNS depression
• Nausea and vomiting
• Hypoglycemia
• Need for frequent serum concentration monitoring

Because of these limitations, ethanol is generally less convenient than fomepizole.

Fomepizole

Fomepizole directly inhibits alcohol dehydrogenase, preventing methanol and ethylene glycol from being converted into their harmful metabolites.

Advantages include:

• Predictable dosing
• Less CNS depression than ethanol
• No need to maintain an intoxicating serum alcohol concentration
• Can be used together with hemodialysis when necessary

Possible adverse effects include:

• Headache
• Nausea
• Dizziness
• Drowsiness
• Altered taste
• IV-site irritation

Hemodialysis

Hemodialysis can rapidly remove both the parent toxic alcohol and important toxic metabolites.

It may be needed in severe poisoning associated with:

• Significant metabolic acidosis
• Kidney failure
• Severe clinical deterioration
• High toxic-alcohol concentrations
• Visual symptoms in methanol poisoning

In ethylene glycol poisoning, dialysis is particularly useful when kidney injury or severe acidosis develops.

In methanol poisoning, dialysis removes both methanol and formate, the metabolite responsible for much of its ocular and systemic toxicity.

Additional Supportive Therapy

For ethylene glycol toxicity:

• Thiamine and pyridoxine may help direct metabolism toward less toxic products

For methanol toxicity:

• Folate or folinic acid may enhance metabolism of formate into less harmful compounds

Key Points

• Fomepizole is the preferred ADH inhibitor in most toxic alcohol poisonings.
• Ethanol works by competing for alcohol dehydrogenase but requires close monitoring and causes more adverse effects.
• Hemodialysis is used for severe methanol or ethylene glycol poisoning, especially with major acidosis or organ dysfunction.
• The major goal of antidotal therapy is to prevent formation of toxic metabolites, not simply to remove the parent alcohol.