Clinical Significance

Acetaminophen is one of two popular non-prescription pain relievers available to the public.  It has analgesic and antipyretic effects like aspirin but little of aspirin's anti-inflammatory properties.  Proper management of acetaminophen overdose requires early monitoring of the patient's serum levels, because toxic drug levels can cause hepatic necrosis which is not clinically evident until 12 or more hours after ingestion; more antidotes are available that can prevent liver damage, if they are administered early.

Treatment of acetaminophen poisoning is primarily based on patient information about time of ingestion and serum levels.  Nomograms have been devised to determine patient's status with one serum sample; the time after ingestion is plotted on the abscissa vs. drug level on the ordinate.  Patient ingestion information is not always reliable and much more accurate method to estimate toxicity is to determine drug half-life.  Acetaminophen half-life is normally 2-3 hours and hepatic damage is likely if it exceeds 4 hours.  Significant liver damage is also considered likely if drug levels are greater than 200 ug/mL at 4 hours after ingestion or 50 ug/mL after 12 hours.  To determine acetaminophen half-life, the first of two specimens should be drawn at least four hours after poisoning to ensure peak levels have been achieved.

N-acetylcysteine, methionine, and cysteamine are commonly administered antidotes, once acetaminophen toxicity has been verified.  Their mode of action is to either bind up the toxic metabolite or stimulate glutathione synthesis in situ.  These have been effective in preventing hepatic necrosis when given up to 8-10 hours after ingestion of acetaminophen overdose.