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Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used class of drugs in the United States, and all share inhibition of the cyclooxygenase enzyme as a mechanism of action. NSAIDs are effective antipyretics, analgesics, and anti-inflammatory agents. Because of their large therapeutic window, acute ingestion with overdoses rarely produces serious complications.1,2 The morbidity from NSAIDs in acute overdose is far overshadowed by complications of NSAIDs at therapeutic doses, which include GI bleeding, drug-induced renal failure, and atherosclerotic heart disease.3,4,5,6 Due to their increased risk for cardiovascular disease, rofecoxib and valdecoxib were withdrawn from the U.S. market in 2004 and 2005, respectively.
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NSAIDs are structurally varied compounds with common therapeutic effects (Table 191-1). NSAIDs reversibly inhibit the enzyme cyclooxygenase, which is responsible for the production of prostaglandins from arachidonic acid (Figure 191-1). The anti-inflammatory effect of NSAIDs is through the inhibition of prostaglandin production, and they may also inhibit neutrophil migration via unclear mechanisms. NSAIDs are antipyretics through inhibition of prostaglandin E2 in the hypothalamus. NSAIDs attenuate prostaglandin-mediated hyperalgesia and local pain fiber stimulus.
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Two isoforms of cyclooxygenase (abbreviated COX-1 and COX-2) vary in presence and distribution.7 COX-1 is present with steady level of activity and is found primarily in blood vessels, kidneys, and stomach. In contrast, COX-2 is not normally found to a significant degree in human tissue with the possible exception of the brain and kidneys, unless its production is induced by local inflammation.
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Cyclooxygenase inhibitors can be categorized as nonselective, partially selective, or selective ...