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INTRODUCTION

The nonsteroidal anti-inflammatory drugs (NSAIDs) are a chemically diverse group of agents that have similar pharmacologic properties and are widely used for their anti-inflammatory, antipyretic, and analgesic properties (Table II–43). Overdose by most of the agents in this group usually produces only mild GI upset. However, toxicity may be more severe after overdose with oxyphenbutazone, phenylbutazone, mefenamic acid, piroxicam, or diflunisal.

TABLE II–43.NSAIDs

MECHANISM OF TOXICITY

  1. NSAIDs produce their pharmacologic and most toxicologic effects by inhibiting the enzyme cyclooxygenase (isoforms COX-1 and COX-2); this results in decreased production of prostaglandins and decreased pain and inflammation. Central nervous system, hemodynamic, pulmonary, and hepatic dysfunction also occurs with some agents, but the relationship to prostaglandin production remains uncertain. Prostaglandins are also involved in maintaining the integrity of the gastric mucosa and regulating renal blood flow; thus, acute or chronic intoxication may affect these organs.

  2. The newest generation of NSAIDs, known as the COX-2 inhibitors, selectively inhibit the COX-2 isoform, with no COX-1 inhibition at therapeutic doses. Because COX-1 is involved in GI mucosal protection, the likelihood of GI bleeding is less with these drugs than with conventional NSAIDs. However, COX-2 selective inhibitors have been associated with an increased risk of cardiovascular disease (both rofecoxib and valdecoxib were voluntarily withdrawn from the US market in 2004 for this reason).

  3. Pharmacokinetics. NSAIDs are generally well absorbed, and volumes of distribution are relatively small (eg, 0.15 L/kg for ibuprofen). COX-2 inhibitors have ...

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