Pathogenesis of NSAID-induced gastroduodenal mucosal injury.
The use of non-steroidal anti-inflammatory drugs (NSAIDs), even in the era of selective COX-2 inhibitors, remains limited by the ability of these agents to cause gastroduodenal ulceration and bleeding. This damage is caused mainly through the ability of these agents to inhibit prostaglandin synthesis, which has a negative impact on several components of mucosal defence. Many NSAIDs also have topical irritant effects on the epithelium which may be particularly important in the production of small intestinal injury. While the presence of acid in the lumen of the stomach may not be a primary factor in the pathogenesis of NSAID-induced gastroenteropathy it can make an important contribution to the chronicity of these lesions and to bleeding by impairing the restitution process, interfering with haemostasis and inactivating several growth factors that are important in mucosal defence and repair. Through better understanding of the pathogenesis of ulcers induced by NSAIDs, some new approaches to the development of more effective and safer anti-inflammatory drugs have been taken in recent years.
Wallace
J L
JL
Mucosal Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases