Cyclo-Oxygenase-2 Inhibitors and the Kidney
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Drug Safety 2002; 25 (3): 165-172 0114-5916/02/0003-0165/$25.00/0 © Adis International Limited. All rights reserved.
Cyclo-Oxygenase-2 Inhibitors and the Kidney A Case for Caution Gary Noroian and David Clive Department of Medicine, Division of Renal Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Cyclo-Oxygenase-2 (COX-2) and its Inhibitors . . . . . . . . . . . . . . 2. COX-2 and the Kidney: the Experimental Evidence . . . . . . . . . . . 2.1 COX-2 and Nephrogenesis . . . . . . . . . . . . . . . . . . . . . . 2.2 Effects of COX-2 Inhibition on Renal Function and Blood Pressure 3. Effects of COX-2 Inhibition on Renal Function and Blood Pressure: Clinical Observations to Date . . . . . . . . . . . . . . . . . . . . . . . 4. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Cyclo-oxygenase (COX) is one of the key enzymes in the biosynthesis of prostaglandins. Two isoforms of this enzyme COX-1 and COX-2 are known to exist. Among other functions, prostaglandins play an important role in the protection of the gastric mucosa and maintenance of renal function in pathophysiological conditions which would otherwise threaten it. Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandin synthesis, resulting in gastric mucosal injury and renal dysfunction in susceptible individuals. The recent introduction of selective COX-2 inhibitors, celecoxib and rofecoxib, appear to induce less gastrointestinal morbidity. Although conclusive data are still lacking, there is evidence to suggest that COX-2 antagonists may be capable of causing some of the same renal syndromes seen in association with the older, less selective NSAIDs.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have become the standard of care in conditions such as rheumatoid arthritis, osteoarthritis, and as a mainstay in the treatment of musculoskeletal pain. In fact, utilisation studies revealed that in 1983 alone, physicians in the US wrote 19.8 million prescriptions for ibuprofen.[1] During this time NSAIDs represented 4% of the entire prescription
market with 473 600kg purchased by pharmacies.[1] At about the same time NSAIDs previously requiring prescriptions became available over-thecounter. In 1999 it was estimated that as many as 30 billion over-the-counter NSAID tablets were sold in the US annually, with regular use by 13 million people with arthridides.[2] However, with such widespread use come widespread adverse
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effects and complications. The clinical spectrum of gastrointestinal injury includes ulcer, haemorrhage, and perforation. In 1997, 16 500 patients with rheumatoid arthritis
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