Methanol and
ethylene glycol poisonings share many characteristics both clinically and biochemically. Both
alcohols are metabolised via
alcohol dehydrogenase to their toxic metabolites.
Methanol is slowly metabolised to
formaldehyde which is rapidly metabolised to
formate, the metabolite mainly responsible for
methanol toxicity.
Formate metabolism depends upon the
folate pool which is small in primates compared with other animals. Therefore,
formate accumulates in primates during
methanol intoxication and is mainly responsible for the
metabolic acidosis in the early stage of intoxication. In late stages
lactate may also accumulate, mainly due to
formate inhibition of the respiratory chain. This tissue
hypoxia caused by
formate may explain the ocular as well as the general toxicity.
Ethylene glycol is metabolised more rapidly than
methanol, via
alcohol dehydrogenase to
glycolaldehyde which is rapidly metabolised to
glycolate, the metabolite mainly responsible for the
metabolic acidosis in
ethylene glycol poisoning.
Glycolate is metabolised by various pathways, including one to
oxalate which rapidly precipitates with
calcium in various tissues and in the urine.
Ethylene glycol toxicity is complex and not fully understood, but is mainly due to the severe
metabolic acidosis caused by
glycolate and to the
calcium oxalate precipitation. The
clinical course in both
poisonings is initially characterised by the development of
metabolic acidosis following a latent period, which is more pronounced in
methanol poisoning and is the time taken for both
alcohols to be metabolised to their toxic metabolites. In
methanol poisoning there are usually visual symptoms progressing to
visual impairment, whereas
ethylene glycol victims develop renal and cardiopulmonary failure. Prognosis is excellent in both
poisonings provided that there is early treatment with
alkali to combat
acidosis,
ethanol as an
antimetabolite, and haemodialysis to remove the
alcohols and their toxic metabolites.
Ethanol is also metabolised by
alcohol dehydrogenase, but has a much higher affinity for this
enzyme than
methanol and
ethylene glycol. Presence of
ethanol will therefore inhibit formation of toxic metabolites from
methanol and
ethylene glycol. Due to competition for the
enzyme, the therapeutic
ethanol concentration depends on the concentration of the other two
alcohols, but a therapeutic
ethanol concentration around 22 mmol/L (100 mg/dl) is generally recommended. Most patients are, however, admitted at a late stage to hospitals not capable of performing analyses of these
alcohols or their specific metabolites on a 24-hour basis.(ABSTRACT TRUNCATED AT 400 WORDS)