What causes increased risk for liver injury in a patient who took acetaminophen after heavy ethanol consumption?

The increased risk for liver injury in a patient who consumes acetaminophen after heavy ethanol intake can primarily be attributed to the induction of cytochrome P450 enzymes. Chronic alcohol consumption activates certain cytochrome P450 isoenzymes, particularly CYP2E1, which enhances the metabolism of acetaminophen. This increased metabolic conversion results in the production of a highly reactive metabolite known as N-acetyl-p-benzoquinone imine (NAPQI).

Under normal circumstances, NAPQI is detoxified by glutathione, but after excessive acetaminophen consumption, or in the presence of alcohol-induced enzymes, glutathione stores can become depleted. This depletion leads to an accumulation of NAPQI, which can bind to cellular proteins and lead to hepatocyte injury and cell death, ultimately resulting in liver damage.

Thus, the induction of cytochrome P450 enzymes by ethanol significantly increases the potential for acetaminophen to cause liver injury due to enhanced formation of its toxic metabolite. This mechanism highlights the importance of understanding drug interactions and the role of liver metabolism in assessing risks associated with combined substance use.