Cimetidine and acetylcysteine as antidote for acetaminophen overdose

The incidence of acetaminophen overdose, often resulting in hepatotoxicity or even death, steadily increases as its use (instead of aspirin) as an antipyretic and analgesic increases. Acetaminophen-induced hepatotoxicity is though to be dependent on the dose ingested and the activity of the cytochrome P450 enzyme system. The actual hepatotoxic mechanism is believed to be the formation of a toxic tissue arylating metabolite(s). Current therapy attempts to inactivate this toxic metabolite(s) with acetylcysteine, as opposed to inhibiting its production. Because cimetidine can inhibit the cytochrome P450 mixed-function oxidase system, we believe it could decrease the production of the hepatotoxic acetaminophen metabolite(s) providing an effective antidote to be used in conjunction with acetylcysteine.