Do selective cyclo-oxygenase inhibitors eliminate the adverse events associated with nonsteroidal anti-inflammatory drug therapy?

Among the most widely prescribed drugs worldwide, non-steroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain, but they are also associated with a high incidence of gastrointestinal (GI) adverse events. Both the beneficial and harmful effects of NSAIDs result from inhibition of the cyclo-oxygenase (COX) enzyme. Recognition of the two distinct COX isoforms prompted development of drugs that selectively block the activity of COX-2, thus providing pain relief and reducing inflammation while sparing COX-1, the enzyme apparently responsible for most protective prostaglandin synthesis in the mucosa of the stomach and duodenum. The results of preclinical and clinical studies indicate that COX-2 inhibitors exhibit high selectivity in inhibiting COX-2, provide excellent pain relief, and cause significantly less GI toxicity than do conventional nonselective NSAIDs. Although they represent a significant advance over nonselective NSAIDs, selective COX-2 inhibitors are not without limitations. They do not completely eliminate GI toxicity or the renal side effects associated with use of conventional NSAIDs. Moreover, in cases of inflammation or ulceration in the GI tract, COX-2 inhibition may delay ulcer healing. Finally, case reports and the results of animal experiments suggest that COX-2 inhibitors may adversely affect ovulation and cause a tendency towards prothrombotic events.