[Gastrointestinal sparing anti-inflammatory drugs--COX-2 selective inhibitors and NO-releasing NSAIDs]

The use of NSAIDs is associated with a wide array of alterations in the gastrointestinal integrity and function. Various approaches have been taken to develop NSAIDs with reduced gastrointestinal toxicity, and few have successfully reduced the incidence of adverse reactions. These include COX-2 selective inhibitors and NO-releasing NSAIDs. Much has been written about the potential of COX-2 inhibitors as antiinflammatory agents that lack the gastrointestinal side effects of traditional NSAIDs. COX-2 expression is most evident at sites of inflammation, while COX-1 accounts for most of the PG synthesis in the normal gastrointestinal tract. However, there are distinct examples of circumstances in which COX-2-derived PGs play a role in the maintenance of the mucosal integrity, and the differentiation of COX-1 and COX-2 is not quite as clear as has been suggested. On the other hand, the rational behind the NO-releasing NSAIDs is that NO released from the derivatives exerts beneficial effects on the gastrointestinal mucosa. The present article overviews the roles of COX and NO in housekeeping functions of the gastrointestinal mucosa in various circumstances and the effects of gastrointestinal sparing NSAIDs, such as COX-2 selective inhibitors and NO-releasing NSAIDs, on the ulcerogenic and healing responses in the gastrointestinal mucosa.