New insights into the mechanism of action of acetaminophen: Its clinical pharmacologic characteristics reflect its inhibition of the two prostaglandin H2 synthases.

a t s o o t Acetaminophen (INN, paracetamol) possesses highly elective analgesic and antipyretic effects that result rom its inhibitory actions on the synthesis of prostalandins (PGs). PGs are lipid mediators derived from rachidonic acid that play central roles in the pathogensis of inflammation, fever, and pain. However, acetminophen differs from the majority of nonsteroidal nti-inflammatory drugs (NSAIDs) and selective inhibtors of prostaglandin H2 synthase (PGHS) 2 because it acks significant antiinflammatory activity. Moreover, s opposed to aspirin, acetaminophen is a poor inhibitor f platelet function at doses that are antipyretic. PGs are generated by the oxygenation of arachidonic cid to the unstable intermediate prostaglandin H2 PGH2) by PGHS, of which there are 2 major isoorms—the constitutive PGHS-1 and the (generally) nducible PGHS-2 (discussed later). These enzymes re also commonly referred to as cyclooxygenase COX) 1 and 2, respectively, in reference to the specific nzymatic active site that catalyzes arachidonic acid xygenation and provides the target for the majority of