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.