How toxic is methanediol

Ethanol's deadly brother

Methanol is not dangerous per se, but its breakdown products formaldehyde and formic acid. If, however, the metabolizing enzyme, alcohol dehydrogenase (ADH), is “busy” breaking down ethanol, methanol is not broken down into toxic metabolites and excreted unchanged. That is why it is more toxic "pure" than in high-proof.

 

Methanol is dangerous in any concentration. Depending on body weight and general condition, amounts from 30 ml can be fatal in adults. At first the substance has an intoxicating effect like ethanol. The first symptoms of poisoning can become noticeable after an hour with headaches, nausea and vomiting. Unfortunately, the first symptoms for the person concerned and those around him can hardly be distinguished from an ordinary intoxication. Later on, severe problems such as blurred vision and loss of consciousness arise. Formaldehyde and formic acid irreparably damage the brain, optic nerves, liver and kidneys; acidosis also develops in the blood. Sustainable organ damage occurs after around 48 to 72 hours. If left untreated, methanol poisoning is often fatal, usually with cardiac arrest and respiratory arrest.

 

Ethanol for therapy

 

If methanol poisoning is suspected, the patient must therefore be hospitalized immediately. As an antidote, he is usually given ethanol intravenously or - if he is conscious - orally. The ethanol concentration in the serum is kept between 0.5 and 1.0 g / l. Since the ADH preferentially breaks down ethanol, it is "employed" until the methanol is eliminated. It can take days.

 

An alternative is fomepizole, which has been available in Germany as an orphan drug since 2006, but is only approved for the treatment of acute ethylene glycol poisoning. The 4-methylpyrazole is a competitive inhibitor of ADH and stops the hepatic breakdown of ethylene glycol or methanol to the toxic metabolites. The parent substances are then excreted renally. The therapy is supplemented by increased diuresis and treatment of acidosis with sodium hydrogen carbonate and, in the case of severe poisoning, hemodialysis. Fomepizole is also approved in the United States for the treatment of methanol poisoning. In Germany this is an off-label use. /