The role of cyclooxygenase selective inhibitors in the gastrointestinal tract.

This article reviews the gastrointestinal manifestations of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and the improved gastrointestinal safety profile of cyclooxygenase selective (COX)-2 inhibitors. By inhibiting the COX enzyme, NSAIDs provide effective analgesia and suppress inflammation in a variety of conditions. Most NSAIDs (nonselective or traditional) not only inhibit prostaglandins at sites of inflammation but also inhibit prostaglandins that have important normal functions in other parts of the body. This may be harmful when normal gastrointestinal mucosal function is impaired and mucosal damage occurs. Although such damage is often trivial and usually not symptomatic, gastrointestinal ulceration may produce pain and, more ominously, lead to bleeding, perforation, or obstruction. A new approach to the gastrointestinal complications of NSAIDs became feasible with the discovery of two isoforms of COX, COX-1 and COX-2, with COX-1 expressed mainly in the gastrointestinal tract. The development of NSAIDs that preferentially inhibit COX-2 offers the promise of relieving pain and inflammation without the side effects attendant to COX-1 blockade. In prospective studies evaluating gastrointestinal ulceration with COX-2-specific NSAIDs, rates of endoscopic ulceration have been equivalent to those with placebo and much lower than those with nonselective NSAIDs. In the recently released studies of gastrointestinal outcomes (perforated, painful, or bleeding ulcers), incidence of clinically relevant ulceration with COX-2 NSAIDs is much lower than that of traditional NSAIDs.