Substrates in Treatment of Some Intoxications

Competitive inhibition is the basis for the treatment of some intoxications (e.g., methyl alcohol, ethylene glycol). Methanol, which is widely used industrially as a solvent, is added to ethanol (ethyl alcohol) to make it unsuitable for human consumption. Such adulterated alcohol is commonly known as denatured alcohol. Methanol is metabolized primarily in the liver and kidney by oxidation to formaldehyde and formic acid  

Major toxic effects are caused by formaldehyde and formic acid. The former is responsible for damage to retinal cells that may cause blindness, while the latter produces severe acidosis that may eventually lead to death. A minor effect of methanol is depression of the central nervous system (CNS). Retardation of the first step in the oxidation of methanol is accomplished by administration of ethanol, the oxidation products of which are not as toxic as those of methanol. Other therapeutic modalities include removal of methanol by gastric lavage (to prevent further absorption), hemodialysis (to remove absorbed methanol), and administration of exogenous bicarbonate (for treatment of severe acidosis). 

Ethylene glycol, which is widely used as an antifreeze for automobile radiators, upon ingestion causes depression of the CNS, metabolic acidosis, and severe renal damage. Its oxidation in the body requires the action of alcohol dehydrogenase  

Kidney damage results from precipitation of oxalate crystals in the convoluted tubules. The elevated anion-gap metabolic acidosis is caused by glycolic acid and lactic acid. The latter is formed from pyruvate due to a shift in the redox potential favoring the production of lactate. The treatment is the same as that for methanol intoxication. 

4-Methylpyrazole (fomepizole), a more effective inhibitor of alcohol dehydrogenase with none of the adverse effects of ethanol, has been used in the treatment of ethylene glycol toxicity. 

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