Evaluation of Novel New NSAIDs: A Review of COX-2 Inhibitors,with an Emphasis on Gastrointestinal Toxicity

Identification of two isoforms of cyclooxygenase, COX-1 and COX-2, has initiated a revolution in the approach to pharmacologie pain management. It has been further determined that inhibition of COX-2 reduces inflammation, and inhibition of COX-1 compromises gastrointestinal mucosal integrity. As traditional nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2, gastrointestinal ulceration can develop in association with the use of these agents to control pain and inflammation. An ideal NSAID would, therefore, inhibit COX-2 to provide anti-inflammatory effects while leaving COX-1, and, therefore, gastrointestinal mucosa, unaffected.

Two selective COX-2 inhibitors have recently been approved in the United States. Celecoxib (Celebrex, G.D. Searle & Co.) and rofecoxib (Vioxxj, Merck & Co., Inc.) are indicated for the treatment of osteoarthritis. Also, celecoxib is approved for rheumatoid arthritis. Rofecoxib is also approved for the treatment of acute pain and dysmenorrhea. Both agents have displayed similar efficacy to traditional NSAIDs. In addition, endoscopically detected gastrointestinal ulceration is reduced versus older NSAIDs. Further evaluation of selective COX-2 inhibitors will elucidate long-term efficacy, safety, and potential reduction of health care dollars spent on hospitalization and treatment for NSAID-induced gastrointestinal toxicity.