Mechanisms of gastric damage by non-steroidal anti-inflammatory drugs

All non-steroidal anti-inflammatory drugs (NSAIDs) used in the treatment of rheumatic diseases may cause gastrointestinal mucosal injury. The mechanisms by which these agents damage mucosa are not fully understood, although, reduction of mucosal defence by the depletion of endogenous, protective prostaglandins has been deemed important. NSAIDs have been shown to decrease the magnitude of the mucus-bicarbonate barrier, disrupt the epithelial cell layer, reduce the surface hydrophobicity of epithelial cells and to diminish mucosal blood flow. Such effects render the mucosa more susceptible to damage by acid, pepsin, bile salts and alcohol. In addition, direct mucosal injury may be caused by the physiochemical properties of NSAIDs, being weak acids. There is now increasing evidence that gastroduodenal mucosa adapts to acute damage by these drugs with mucosal injury recovering during continued administration. The mechanisms governing such adaptation remain unknown and require further investigation.