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Article

Cyclooxygenase-2–selective inhibitors: Translating pharmacology into clinical utility

Bruce N. Cronstein, MD
Cleveland Clinic Journal of Medicine April 2002, 69 (4 suppl 1) SI-13-SI-19;
Bruce N. Cronstein
New York University School of Medicine, New York.
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ABSTRACT

Anti-inflammatory agents have been used for centuries, but only in the last few decades has medical science gained insight into the complex biologic roles of the primary mediators of inflammation, the eicosanoids and their derivatives. Detailed understanding of the prostaglandins and leukotrienes provides a framework for the treatment of pain, inflammation, and fever with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), but these agents have exacted a substantial side effect burden. The discovery of cyclooxygenase-2 (COX-2) has guided development of rationally designed therapeutic agents that have the benefits of older NSAIDs with reduced gastrointestinal toxicity. Elucidation of the structure of COX isoenzymes has been key in the development of coxibs, the COX-2–selective subset of NSAIDs. Methods to determine the degree of COX-2 selectivity have been refined and are indispensable for comparing the relative selectivity of these agents. This review summarizes some of the key aspects of COX biochemistry, structure, and function and the evolution of understanding the mechanism of action of COX-2–selective inhibitors. The clinical relevance of COX-1 compared with COX-2 inhibition is discussed to provide a framework upon which clinicians can better appreciate current and future therapeutic applications of coxibs.

  • Copyright © 2002 The Cleveland Clinic Foundation. All Rights Reserved.
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Cleveland Clinic Journal of Medicine: 69 (4 suppl 1)
Cleveland Clinic Journal of Medicine
Vol. 69, Issue 4 suppl 1
1 Apr 2002
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Cyclooxygenase-2–selective inhibitors: Translating pharmacology into clinical utility
Bruce N. Cronstein
Cleveland Clinic Journal of Medicine Apr 2002, 69 (4 suppl 1) SI-13-SI-19;

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Cyclooxygenase-2–selective inhibitors: Translating pharmacology into clinical utility
Bruce N. Cronstein
Cleveland Clinic Journal of Medicine Apr 2002, 69 (4 suppl 1) SI-13-SI-19;
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