Cyclooxygenase-2 specificity and its clinical implications.

ABSTRACT

Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce pain and inflammation by inhibiting the synthesis of prostanoids. However, these drugs inhibit both cyclooxygenase-1 (COX-1), which is essential for the regulation of homeostasis in many tissues, as well as COX-2, which is an important mediator of pain and inflammation. Disruption of COX-1 enzymatic activity by NSAIDs leads to such side effects as interference with platelet functions and gastric ulcers. The recent development of COX-2-specific inhibitors, such as celecoxib, raises the possibility of relieving pain and inflammation with reduced risk of gastrointestinal complications. In Phase II and III studies, celecoxib has demonstrated efficacy in alleviating dental pain and the signs and symptoms of osteoarthritis and rheumatoid arthritis. This COX-2-specific inhibitor was also associated with a markedly lower rate of gastroduodenal injury than is seen typically with NSAIDs. Incidence of most adverse events (including gastrointestinal) and withdrawal rates resulting from adverse events with celecoxib were similar to placebo. Celecoxib appears to be both safe and effective in the treatment of osteoarthritis and rheumatoid arthritis. Its COX-2-specific inhibitory properties thus introduce the possibility of effective relief of arthritic and other types of pain and inflammation with less risk of the mechanism-based toxicities observed with conventional NSAIDs.