text: Acetaminophen (APAP) is a very common drug used to treat pain. High doses of acetaminophen has been shown to produce severe hepatotoxicity after being biotransformed to produce reactive intermediates. Acetaminophen is metabolized by CYP2E1 to produce NAPQI, which then causes significant oxidative stress due to increased reactive oxygen species (ROS). ROS can cause cellular damage in a multitude of ways, a few of which being DNA and mitochondrial damage and depletion of antioxidant enzymes such as glutathione. In terms of drug-drug interactions, acetaminophen activates CAR, a nuclear receptor involved in the production of metabolic enzymes, which increases the metabolism of other drugs. This could either cause reactive intermediates/drug activity to persist for longer than necessary, or the drug will be cleared quicker than normal and prevent any therapeutic actions from occurring. Ethanol induces CYP2E1 enzymes in the liver, which can lead to increased NAPQI formation in addition to that formed by acetaminophen.