Author: Wallace, John L.

Source: Inflammation & Allergy - Drug Targets, Volume 5, Number 2, April 2006 , pp. 133-137(5)

Publisher: Bentham Science Publishers

Abstract:

The use of nonsteroidal anti-inflammatory drugs is associated with an incidence of severe gastrointestinal adverse events of 2-4%, the most common of which is bleeding. These events are largely attributable to the ability of these drugs to suppress prostaglandin and thromboxane synthesis. Prostaglandins perform a number of important functions in the gastrointestinal tract, particularly with respect to resistance of the mucosa to injury. Nitric oxide also appears to be a key mediator of gastrointestinal mucosal defence, and this has been exploited in the development of a novel class of anti-inflammatory drugs, called "NO-NSAIDs", which exhibit little if any gastrointestinal toxicity. NONSAIDs are more effective than traditional NSAIDs in reducing pain and inflammation. Another class of inflammatory mediators that contribute to gastrointestinal mucosal defence are the lipoxins. These products of arachidonic acid metabolism can increase the resistance of the stomach to the damaging effects of aspirin. Indeed, aspirin can trigger the formation of a lipoxin by the stomach which acts to diminish the damaging effects of this drug. Lipoxins and nitric oxide are important mediators of mucosal defence in the stomach (and elsewhere in the gastrointestinal tract) and represent attractive therapeutic targets for reducing the incidence of gastric ulceration.

Keywords: Ulcer; nonsteroidal anti-inflammatory drugs; inflammation; prostaglandins; mucosal defence; neutrophil

Document Type: Research article

DOI: http://dx.doi.org/10.2174/187152806776383116

Affiliations: 1: Department of Pharmacology & Therapeutics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada.

Publication date: 2006-04-01

More about this publication?

• Inflammation & Allergy - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in inflammation and allergy e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in inflammation and allergy. As the discovery, identification, characterization and validation of novel human drug targets for anti-inflammation and allergy drug discovery continues to grow, this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

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