Nonopioids: NSAIDs, Selective Cyclooxygenase-2 Inhibitors, and Acetaminophen
Nonsteroidal antiinflammatory drugs have good analgesic efficacy (but often less than that of opioids), relatively rapid onset, and adverse effects (eg, possibly fatal gastrointestinal bleeding and disturbed salt and water balance). All NSAID effects—analgesic, antiinflammatory, antipyretic, and antiplatelet—are thought to be due to decreased prostanoid biosynthesis via COX inhibition. Traditional NSAIDs inhibit both COX1 and 2 isoforms, but newer COX2 inhibitors are more selective. The analgesic efficacy of selective COX2 inhibitors (coxibs) is approximately equal to that of traditional NSAIDs, but the adverse effects of COX2 inhibition have yet to be fully characterized and are somewhat controversial. The ability to selectively inhibit COX2 has been related to the difference in amino acids at position 523 of COX1 and COX2: isoleucine in COX1, valine in COX2. The mechanism of action of acetaminophen is uncertain but is thought to be via CNS effects.