Acetaminophen: a practical pharmacologic overview.
Acetaminophen is an effective analgesic and antipyretic agent with few adverse effects when used in recommended dosages. The drug is metabolized mainly in the liver, and the several end products have no harmful effects. An intermediate compound in a minor metabolic pathway, however, is toxic; it is normally inactivated by glutathione. In the case of an acetaminophen overdose the hepatic stores of glutathione seem to become depleted, leaving the toxic intermediate free to damage liver tissue. Such damage is unlikely to occur unless the plasma concentration of acetaminophen peaks above 150 micrograms/mL--a level far in excess of the 5 to 20 micrograms/mL achieved with therapeutic doses of the drug. Long-term therapeutic use of acetaminophen does not appear to be associated with liver damage, although some case reports suggest the possibility. Acetaminophen poisoning follows an acute overdose and, if untreated, is manifested clinically by an initial phase of nonspecific signs and symptoms, a latent period in which the liver transaminase levels rise and then, 3 to 5 days after the ingestion, signs of more serious hepatic dysfunction. Most patients do not progress beyond the first or second phase. They and those who survive the third phase recover with no residual injury to the liver. Appropriate antidotal therapy markedly reduces the severity of the initial damage.
D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005334:Fever / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008657:Metabolic Clearance Rate; D010146:Pain / Q000188:drug therapy*
D000082:Acetaminophen