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INTRODUCTION

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used therapeutic agents in the United States. 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.3-6

PHARMACOLOGY

NSAIDs are structurally varied compounds with common therapeutic effects (Table 191-1). NSAIDs reversibly inhibit COX, which is responsible for the production of prostaglandins from arachidonic acid. The anti-inflammatory effect of NSAIDs is through the inhibition of prostaglandin production and neutrophil migration.7 NSAIDs are antipyretics via inhibition of prostaglandin E2 in the hypothalamus. Analgesia is mediated by attenuation of prostaglandin-mediated hyperalgesia and local pain fiber stimulus.

TABLE 191-1Nonsteroidal Agents Available in the United States

CYCLOOXYGENASE

Two isoforms of COX (COX-1 and COX-2) vary in presence and distribution.8 COX-1 is present with a steady level of activity and is found primarily in blood vessels, kidneys, and the stomach. In contrast, COX-2 is found in low levels in human tissue unless induced by proinflammatory mediators.8

COX inhibitors can be categorized as nonselective, partially selective, or selective regarding their inhibition of COX enzyme isoforms (Table 191-1). Most NSAIDs nonselectively inhibit both COX-1 and COX-2. COX-1 inhibition is responsible for most of the unwanted GI side effects of NSAIDs. Drugs such as etodolac and meloxicam were created ...

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