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NSAIDs are among the most widely used and prescribed drugs in the U.S. This class contains approximately 20 drugs that share inhibition of the cyclooxygenase enzyme as a mechanism of action. Although this class also contains acetaminophen and salicylates, these two drugs possess unique toxicity and are considered in separate chapters (see Chapter 183, Aspirin and Salicylates, and Chapter 184, Acetaminophen). NSAIDs are effective antipyretics, analgesics, and anti-inflammatory agents. Because of their large therapeutic window, NSAIDs are relatively safe agents with respect to acute ingestion and overdose, rarely producing serious complications.1–3 Several agents are now available without prescription (over the counter), and the world sales for NSAIDs is reported to be $6 billion per year in U.S. dollars.4

During 2008, the American Association of Poison Control Centers received reports of 107,115 NSAID exposures (excluding aspirin and acetaminophen) resulting in 65 (0.05%) major outcomes (life-threatening signs and symptoms or significant residual disability).5 There were 44 deaths where NSAIDs were mentioned and 5 deaths associated with single exposure. This experience compares favorably with the toxicity reported with isolated aspirin or acetaminophen ingestions during 2008: 99,210 exposures with 84 deaths.5 It should be remembered that poison center data are gathered passively and likely underrepresent the true number of exposed persons. The morbidity from NSAIDs in acute overdose is far overshadowed by complications of NSAIDs at therapeutic doses, including GI bleeding, drug-induced renal failure, and ischemic heart disease.6–8 Due to an increased risk for cardiovascular disease with therapeutic doses, the selective cyclooxygenase-2 inhibitors rofecoxib and valdecoxib were withdrawn from the U.S. market in 2004 and 2005, respectively.


NSAIDs are structurally varied compounds with common therapeutic effects (Table 185-1). With the exception of aspirin and other salicylates, NSAIDs reversibly inhibit the enzyme cyclooxygenase, which is responsible for the production of prostaglandins from arachidonic acid (Figure 185-1). The anti-inflammatory effect of NSAIDs is through the inhibition of prostaglandin production, but they may also inhibit neutrophils via mechanisms unrelated to prostaglandin. NSAIDs work as antipyretics through inhibition of prostaglandin E2 in the hypothalamus. NSAIDs also appear to attenuate prostaglandin-mediated hyperalgesia and local pain fiber stimulus.

Table 185-1 Classes of Nonsteroidal Agents Available in the U.S.

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