Pathogenesis of NSAID-induced gastroduodenal mucosal injury

Best Pract Res Clin Gastroenterol. 2001 Oct;15(5):691-703. doi: 10.1053/bega.2001.0229.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / adverse effects*
  • Duodenum / drug effects*
  • Duodenum / metabolism
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / metabolism
  • Humans
  • Intestinal Mucosa / drug effects
  • Isoenzymes / antagonists & inhibitors
  • Membrane Proteins
  • Peptic Ulcer / chemically induced*
  • Peptic Ulcer / metabolism
  • Prostaglandin-Endoperoxide Synthases
  • Prostaglandins / biosynthesis

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Prostaglandins
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases