Gastroduodenal ulceration and
bleeding are the major limitations to the use of non-steroidal anti-inflammatory drugs (
NSAIDs). The development of safer
NSAIDs or of effective
therapies for the prevention of the adverse effects of existing
NSAIDs requires a better understanding of the pathogenesis of
NSAID-induced
ulcer disease.
NSAIDs can cause damage to the gastroduodenal mucosa via several mechanisms, including the topical
irritant effect of these drugs on the epithelium, impairment of the barrier properties of the mucosa, suppression of gastric
prostaglandin synthesis, reduction of gastric mucosal blood flow and interference with the repair of superficial injury. The presence of
acid in the lumen of the stomach also contributes to the pathogenesis of
NSAID-induced
ulcers and
bleeding, by impairing the restitution process, interfering with haemostasis and inactivating several
growth factors that are important in mucosal defence and repair. In recent years, a fuller understanding of the pathogenesis of
NSAID-induced
ulcer disease has facilitated some new, very promising approaches to the development of stomach-sparing
NSAIDs.