Review article: cellular and molecular mechanisms of NSAID-induced peptic ulcers.
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most prescribed drugs worldwide and have now probably overtaken Helicobacter pylori as the most common cause of gastrointestinal injury in Western countries. Further understanding of the pathogenesis of NSAID-induced ulcers is important to enable the development of novel and effective preventive strategies.


OBJECTIVE
To provide an update on recent advances in our understanding of the cellular and molecular mechanisms involved in the development of NSAID-induced ulcers.


METHODS
A Medline search was performed to identify relevant literature using search terms including 'nonsteroidal anti-inflammatory drugs, aspirin, gastric ulcer, duodenal ulcer, pathogenesis, pharmacogenetics'.


RESULTS
The mechanisms of NSAID-induced ulcers can be divided into topical and systemic effects and the latter may be prostaglandin-dependent (through COX inhibition) or prostaglandin-independent. Genetic factors may play an important role in determining individual predisposition.


CONCLUSIONS
The pathogenesis of NSAID-induced peptic ulcers is complex and multifactorial. Recent advances in cellular and molecular biology have highlighted the importance of various prostaglandin-independent mechanisms. Pharmacogenetic studies may provide further insights into the pathogenetic mechanisms of NSAID-induced ulcers and help identify patients at increased risk.
Musumba
C
C
Department of Pharmacology and Therapeutics, School of Biomedical Sciences, University of Liverpool, Liverpool, UK.
Pritchard
D M
DM
Pirmohamed
M
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D002986:Clinical Trials as Topic; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D010437:Peptic Ulcer / Q000139:chemically induced*; D011453:Prostaglandins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011453:Prostaglandins