Toward More GI-Friendly Anti-Inflammatory Medications.

OPINION STATEMENT: Despite the introduction 20-30 years ago of potent inhibitors of gastric acid secretion and anti-inflammatory drugs that preferentially inhibit cyclo-oxygenase (COX)-2, the GI adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) remain a significant clinical concern and a considerable economic burden. Inhibitors of acid secretion and selective COX-2 inhibitors reduce damage only in the proximal GI tract (stomach and proximal duodenum), but NSAIDs produce injury and bleeding throughout the GI tract. The small intestinal damage caused by NSAIDs is common, difficult to diagnose, and there are no proven-effective preventative or curative therapies. There is also emerging evidence that proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs) exacerbate NSAID-induced small intestinal injury. A new approach to solve this clinical problem is to deliver an endogenous, cytoprotective "rescue molecule" together with a COX inhibitor. Hydrogen sulfide (H2S) is a naturally produced, potent protective agent in the GI tract. H2S-releasing NSAIDs have been synthesized and extensively tested in laboratory animals and humans. They exhibit improved anti-inflammatory activity over the parent NSAID, while causing negligible damage in the GI tract.