A 3-year-old girl was brought into the Emergency Room. She was cold and clammy and was breathing rapidly. She was obviously confused and lethargic. Her mother indicated that she had accidentally ingested automobile antifreeze (ethylene glycol) while playing in the garage. Following gastrointestinal lavage and activated charcoal administration, a nasogastric tube for ethanol was administered. How will ethanol help in relieving the symptoms?
A. Conjugate with ethylene glycol to form a soluble compound
B. Induce the alcohol dehydrogenase enzyme
C. Competitively inhibit the metabolism of ethylene glycol
D. Promote the excretion of metabolite of ethylene glycol
E. All of the above.
The correct answer is- C- Competitively inhibits the metabolism of ethylene glycol.
Ethylene glycol is the major ingredient of almost all radiator fluid products. It is used to increase the boiling point and decrease the freezing point of radiator fluid, which circulates through the automotive radiator. Ethylene glycol is added to prevent the radiator from overheating or freezing, depending on the season.
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. This glycolate is then transformed into glyoxylic acid. At this point, the molecule may be transformed into the highly toxic oxalate.
Figure- Metabolism of ethylene glycol
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.
Treatment of ethylene glycol poisoning
Emergency and Supportive Measures
For patients presenting within 30–60 minutes after ingestion, the stomach is emptied by gastric lavage. Charcoal is not very effective but should be administered if other poisons or drugs have also been ingested.
Patients with significant toxicity (manifested by severe metabolic acidosis, altered mental status, and markedly elevated osmolar gap) should undergo hemodialysis as soon as possible to remove the parent compound and the toxic metabolites. Treatment with folic acid, thiamine, and pyridoxine may enhance the breakdown of toxic metabolites.
Ethanol blocks metabolism of the parent compounds by competing for the enzyme alcohol dehydrogenase. The desired serum ethanol concentration is 100 mg/d. Fomepizole (4-methylpyrazole; Antizol), blocks alcohol dehydrogenase and can be used instead of ethanol.
As regards other options
Alcohol does not form any complex with ethylene glycol, it does not induce alcohol dehydrogenase enzyme and even it does not promote the excretion of metabolites of ethylene glycol.
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