Ethylene glycol (a component of antifreeze) is toxic and the cause of many cases of accidental and intentional poisoning. One effective treatment for ethylene glycol poisoning is the administration of an intoxicating dose of alcohol. Can you explain how this treatment works?
As with ethyl alcohol and methanol, ethylene glycol is metabolized by alcohol dehydrogenase to form glycoaldehyde. Through interaction with aldehyde dehydrogenase, ethylene glycol is then metabolized to glycolic acid (GA). A profound acidosis often ensues and is attributable to the glycolic acid in circulation. The patient may develop hyperventilation that results from acidemia. This glycolate is then transformed into glyoxylic acid. At this point, the molecule may be transformed into the highly toxic oxalate or the safer glutamate or a -ketoadipic acid metabolites. The administration of particular vitamins may promote the formation of these safer metabolites.
With the formation of oxalate crystals in the urine, calcium oxalate crystals form and accumulate in blood and other tissues. The precipitation of calcium oxalate in the renal cortex results in decreased glomerular filtration and renal insufficiency. Calcium is consumed in circulation, and hypocalcemia may occur.
The rate-dependent step of ethylene glycol metabolism is the alcohol dehydrogenase–catalyzed step. Ethyl alcohol binds much more easily to alcohol dehydrogenase than ethylene glycol or methanol does. Because ethanol is the preferential substrate for alcohol dehydrogenase, the presence of ethanol may essentially block metabolism of ethylene glycol.
Antizol (fomepizole) is a new agent with a specific indication by the U.S. Food and Drug Administration for the treatment of ethylene glycol poisoning. Antizol is a competitive inhibitor of alcohol dehydrogenase, the enzyme that catalyzes the oxidation of ethanol to acetaldehyde. Alcohol dehydrogenase also catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites.