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NSAIDs are among the most widely used medications, but the side effects of these drugs frequently include gastrointestinal (GI) ulceration and bleeding. COX-2 inhibitors were designed that were claimed to be devoid of ulcer-promoting effects; however, this promise has been unfulfilled, and there are concerns about the cardiovascular safety of COX-2 inhibitors. Several novel approaches to developing GI-sparing NSAIDs have been used, with promising preclinical and clinical results. Selective inhibition of terminal PG synthases, and NSAIDs modified to slowly release gastroprotective gaseous mediators (ie, nitric oxide or hydrogen sulfide) may offer renewed hope for developing anti-inflammatory therapies with greatly reduced GI toxicity.

NSAID-Induced Gastrointestinal Damage and the Design of GI-Sparing NSAIDs