Non-steroidal anti-inflammatory drugs (NSAIDs) and gastro-intestinal toxicity: Current issues

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely us ed drugs and their widespread use is associated with increased gastro-intes tinal toxic effects such as ulceration, haemorrhage, perforation and death. They result in these complications mainly by reducing cytoprotective prost aglandins (PGE(2) and PGI(2)) in the stomach, through the inhibition of cyc looxygenase (COX) enzyme. The increased morbidity and mortality, in additio n to enormous cost, associated with NSAID-associated side effects, necessit ates a need for safer GI-friendly NSAID. Various approaches have been used to counteract NSAID associated side effec ts with varying degrees of success and acceptance. These include the use of alternative analgesia, anti-acid secretory agents like proton pump inhibit ors, sucralfate and prostaglandin analogues. In addition, new types of NSAI Ds are being developed, based on new understanding of their mechanism of ac tion and the pathogenesis of inflammation. These include a new class of NSA IDs called "selective Cox-2 inhibitors". These agents preserve the COX-1 th at is responsible for the production of cytoprotective prostaglandins in th e stomach and selectively inhibit COX-2 induced at the sites of inflammatio n. Selective COX-2 inhibitors exert the same analgesic and anti-inflammator y effects as the existing NSAIDs but may be less toxic to the stomach. In t his review the background development and well-structured clinical trials o n this new generation NSAIDs are discussed.