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COX-1, COX-2 and the topical effect in NSAID-induced enteropathy

COX-1, COX-2 and the topical effect in NSAID-induced enteropathy The side effects of NSAIDs are equally evident in the stomach and the small bowel. The latter is increasingly seen as being clinically significant, contributing substantially to the iron-deficiency anaemia that is so common in patients with rheumatoid arthritis. Furthermore, NSAID-enteropathy may be associated with life-threatening events. The pathogenesis of NSAID-enteropathy is uncertain but inhibition of COX-1 is believed to be of pivotal importance. However there is increasing evidence that COX-2 inhibition and the topical effect may have a synergistic detrimental action. We examined the role of COX-1, COX-2 and the so called topical effect of acidic NSAIDs. We found that COX-1 or COX-2 inhibition and the topical effect alone do not damage the GI tract. Dual inhibition of COX-1 and COX-2 results in intestinal inflammation similar to that caused by Indomethacin. The topical effect may act synergistically in this damage. The conventional view that the mechanism of gastrointestinal damage is principally caused by COX-1 inhibition needs to be revised in view of recent studies using selective inhibitors of the COX enzymes and COX knockout animals. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Inflammopharmacology Springer Journals

COX-1, COX-2 and the topical effect in NSAID-induced enteropathy

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References (50)

Publisher
Springer Journals
Copyright
Copyright © 2003 by VSP 2003
Subject
Biomedicine; Pharmacology/Toxicology; Allergology; Rheumatology
ISSN
0925-4692
eISSN
1568-5608
DOI
10.1163/156856003322699546
pmid
15035790
Publisher site
See Article on Publisher Site

Abstract

The side effects of NSAIDs are equally evident in the stomach and the small bowel. The latter is increasingly seen as being clinically significant, contributing substantially to the iron-deficiency anaemia that is so common in patients with rheumatoid arthritis. Furthermore, NSAID-enteropathy may be associated with life-threatening events. The pathogenesis of NSAID-enteropathy is uncertain but inhibition of COX-1 is believed to be of pivotal importance. However there is increasing evidence that COX-2 inhibition and the topical effect may have a synergistic detrimental action. We examined the role of COX-1, COX-2 and the so called topical effect of acidic NSAIDs. We found that COX-1 or COX-2 inhibition and the topical effect alone do not damage the GI tract. Dual inhibition of COX-1 and COX-2 results in intestinal inflammation similar to that caused by Indomethacin. The topical effect may act synergistically in this damage. The conventional view that the mechanism of gastrointestinal damage is principally caused by COX-1 inhibition needs to be revised in view of recent studies using selective inhibitors of the COX enzymes and COX knockout animals.

Journal

Inflammopharmacology – Springer Journals

Published: Dec 22, 2004

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