Methyl Alcohol

METHYL ALCOHOL

(Methanol, Wood alcohol)

Methyl alcohol is added to rectified spirit to render it unfit for drinking. It is only of toxicological importance. Unscrupulous mixing of methylated spirit with alcoholic beverages or its inadvertent ingestion results in methanol poisoning.

Methanol is metabolized to formaldehyde and formic acid by alcohol and aldehyde dehydrogenases respectively, but the rate is 1/₇th that of ethanol. Like ethanol, it follows zero order kinetics and t½ of 20–60 hours has been measured.

Methanol also is a CNS depressant, but less potent than ethanol. Toxic effects of methanol are largely due to formic acid, since its further metabolism is slow and folate dependent. A blood level of >50 mg/dl methanol is associated with severe poisoning. Even 15 ml of methanol has caused blindness and 30 ml has caused death; fatal dose is regarded to be 75–100 ml.

Manifestations of methanol poisoning are vomiting, headache, epigastric pain, uneasiness, dyspnoea, bradycardia and hypotension. Delirium may occur and the patient may suddenly pass into coma. Acidosis is prominent and entirely due to production of formic acid. The specific toxicity of formic acid is retinal damage. Blurring of vision, congestion of optic disc followed by blindness always precede death which is due to respiratory failure.

Treatment

1.   Keep the patient in a quiet, dark room; protect the eyes from light.

2.   Gastric lavage with sod. bicarbonate if the patient is brought within 2 hours of ingesting methanol. Supportive measures to maintain ventilation and BP should be instituted.

3. Combat acidosis by i.v. Sod. bicarbonate infusion—the most important measure; prevents retinal damage and other symptoms; large quantities may be needed.

4.   Pot. chloride infusion is needed only when hypokalemia occurs due to alkali therapy.

5. Ethanol 100 mg/dl in blood saturates alcohol dehydrogenase and retards methanol metabolism. This helps by reducing the rate of generation of toxic metabolites. Ethanol (10% in water) is administered through a nasogastric tube; loading dose of 0.7 ml/kg is followed by 0.15 ml/kg/hour drip. Because pharmacokinetics of alcohol is unstable and no i.v. formulation is available, maintenance of effective concentration is difficult and needs to be repeatedly measured. Moreover, the enzyme saturating concentration of ethanol itself produces intoxication and can cause hypoglycaemia. Treatment has to be continued for several days because the sojourn of methanol in body is long.

6.   Haemodialysis: clears methanol as well as formate and hastens recovery.

7. Fomepizole (4methylpyrazole) is a specific inhibitor of alcohol dehydrogenase—retards methanol metabolism. A loading dose of 15 mg/kg i.v. followed by 10 mg/kg every 12 hours till serum methanol falls below 20 mg/dl, has been found effective and safe. It has several advantages over ethanol, like longer t½ and lack of inebriating action, but is not available commercially in India.

8.   Folate therapy: Calcium leucovorin 50 mg injected 6 hourly has been shown to reduce blood formate levels by enhancing its oxidation. This is a promising adjuvant approach.

Ethylene Glycol Poisoning

Ethylene glycol poisoning has occurred sporadically, especially among children. It is an industrial solvent, coolant and antifreeze. It is oxidized in the body by alcohol dehydrogenase to glycoaldehyde and then to glycolic acid—glyoxylic acid— oxylic acid in steps. Ethylene glycol itself can cause intoxication similar to ethanol, but generation of metabolites results in acidosis, cardiopulmonary complications and renal tubular necrosis.

Fomepizole used in the same manner as for methanol poisoning is the drug of choice. It is approved by USFDA for this indication and has ‘orphan drug status’. Ethanol is employed as an alternative.