Author: Crofford, L.J.

Source: Current Pharmaceutical Design, Volume 6, Number 17, 1 November 2000 , pp. 1725-1736(12)

Publisher: Bentham Science Publishers

Abstract:

The common mechanism of action of aspirin and the chemically unrelated non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of prostaglandin (PG) production due to interference with the enzymatic activity of cyclooxygenase (COX). These agents have long been used as effective treatments for arthritis. The recognition that the inducible isoform COX-2 was associated with inflammation and arthritis led to the hypothesis that PGs produced by a COX-2-dependent pathway were responsible for the inflammation, pain, and tissue destruction. Since the constitutive COX-1 enzyme was identified as responsible for gastroprotection and inhibition of platelet function, the potential for compounds that were both effective and safer than NSAIDs led to rapid development of agents that specifically inhibit COX-2. These agents have now been tested and approved for use by the US Food and Drug Administration for patients with osteoarthritis and rheumatoid arthritis. They have been shown equally effective to comparitor NSAIDs. More importantly, there is a 3.5-fold reduction in the incidence of endoscopic gastroduodenal ulcerations and early data suggesting a similar reduction in clinically significant perforations, symptomatic ulcers, and bleeds. In patients with arthritis at risk for gastrointestinal complications of NSAIDs, specific inhibitors of COX-2 provide an effective and apparently safer form of anti-inflammatory agent.

Keywords: COX 2 Inhibitors in Arthritis; Inhibition of prostaglandin; Cyclooxygenase; Symptomatic Ulcers; Prostaglandin PG; Thromboxanes TX; Rheumatoid Arthritis; Phospholipase A2; Synovial cells; Celecoxib(EPS); Rofecoxib; Streptococcal cell wall SCW

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1381612003398753

Publication date: 2000-11-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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