ETOH and acetaminophen toxicity

Q: Ingestion of alcohol and acetaminophen together increases the risk of acute acetaminophen toxicity by many folds?

A) True

B) False

Answer: B

It may be of surprise but acute alcohol ingestion may be protective against acute acetaminophen toxicity. This is due to the fact that alcohol is a substrate of the CYP2E1 enzyme. It may lower the risk by almost two-third. Alcohol competes with acetaminophen for CYP2E1 and decreases the amount of NAPQI produced. 

CYP2E1 is a member of the cytochrome P450 mixed-function oxidase system, and NAPQI is N-acetyl-p-benzoquinone imine, a toxic byproduct produced during acetaminophen metabolism.

#toxicology

References:

1. Thummel KE, Slattery JT, Nelson SD. Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen. J Pharmacol Exp Ther 1988; 245:129. 

2. Slattery JT, Nelson SD, Thummel KE. The complex interaction between ethanol and acetaminophen. Clin Pharmacol Ther 1996; 60:241. 

3. Waring WS, Stephen AF, Malkowska AM, Robinson OD. Acute ethanol coingestion confers a lower risk of hepatotoxicity after deliberate acetaminophen overdose. Acad Emerg Med 2008; 15:54.