**12. Adverse drug reactions associated with drug biotransformation reactions**

Many adverse drug reactions can be traced to an improper balance between bioactiva‐ tion and detoxification reactions. For example, when the analgesic acetaminophen is giv‐ en at normal therapeutic doses, it undergoes glucuronidation and sulfation reactions that terminate the action of the drug and hasten its elimination. However, some of the drug is bioactivated via Cyt P450 to form N-acetylbenzoquinimine, a reactive intermediate that can be detoxified by conjugation with glutathione (GSH). When excessive doses of the drug are given, glucuronidation and sulfation reactions become saturated and more acet‐ aminophen is bioactivated via Cyt P450. This imbalance leads to high concentrations of Nacetylbenzoqunonine which cannot be sufficiently eliminated by the limited concentrations of gluthathione. This metabolite binds covalently to cellular protein thiols and initiates hepatotoxicity leading to hepatic necrosis.
