Assessment and prevention of gastrointestinal toxicity of non-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for analgesic, anti-inflammatory and, in the case of aspirin, for anti-thrombotic actions. The serious gastrointestinal side-effects associated with these drugs are of concern and pose a significant obstacle to their use. This review discusses the pathogenic mechanisms by which the conventional acidic NSAIDs induce gastrointestinal toxicity, with particular emphasis on non-prostaglandin effects. Methods of assessment of NSAID-induced enteropathy are reviewed, with particular emphasis on the use of functional measurement of NSAID-induced changes in the gastrointestinal tract. The advances in our knowledge of the pathogenesis of these effects have resulted in the development of a range of novel NSAIDs. Where functional assessment of the effects of NSAIDs has been employed, it appears to be more useful as an indicator of early-stage changes rather than a predictor of the effects of long-term NSAID exposure. Successful pharmaceutical strategies now offer considerable promise for reducing the severity of NSAID damage to the gastrointestinal tract. The utility of intestinal permeability measurements for selection and assessment of these strategies is discussed.