COX - 2 Inhibitors , Other NSAIDs , and Cardiovascular Risk

The concept was appealing in its simplicity. Traditional nonsteroidal antiinflammatory drugs (NSAIDs) inhibited both isoforms of the enzyme cyclooxygenase responsible for the first step in the conversion of arachidonic acid into a variety of prostaglandins, thromboxanes, and leukotrienes throughout the body. The anti-inflammatory and pain-relieving effects of NSAIDs resulted from inhibition of prostaglandin synthesis mediated by cyclooxygenase 2 (COX-2) at the site of tissue injury, while gastrointestinal tract complications were due to inhibition of prostaglandin synthesis mediated by cyclooxygenase 1 (COX-1) in the gastrointestinal mucosa. The allure of COX-2 inhibitors was the prospect of treating pain without gastrointestinal toxicity. Celecoxib and rofecoxib were the first of these new agents to gain approval and, with heavy promotion and direct-to-consumer advertising, quickly became the most widely prescribed NSAIDs in the United States.