NSAID gastroenteropathy: past, present and future.
The toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) in the gastrointestinal tract continues to be a major limitation to their use in the treatment of inflammatory disorders. Better understanding of the pathogenesis of NSAID enteropathy has facilitated the development of novel NSAIDs that spare the gastrointestinal tract. In particular, identification and characterization of the inducible form of prostaglandin synthase has led to the design of novel NSAIDs that specifically target that enzyme. The pathogenesis of NSAID gastroenteropathy is reviewed, as are the strategies that have been used in the past and are used now to develop NSAIDs that spare the gastrointestinal tract. Also reviewed are the strategies being employed to achieve this goal in the future.
Wallace
J L
JL
Intestinal Disease Research Unit, Faculty of Medicine, University of Calgary, Alberta. wallacej@acs.ucalgary.ca
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D001241:Aspirin / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D018890:Chemoprevention; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D005544:Forecasting; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000145:classification / Q000187:drug effects / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin