Blog
About

3
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Renal Effects of COX-2-Selective Inhibitors

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Although nonsteroidal anti-inflammatory drugs (NSAIDs) effectively treat a variety of inflammatory diseases, these agents may cause deleterious effects on kidney function, especially with respect to solute homeostasis and maintenance of renal perfusion and glomerular filtration. NSAIDs act by reducing prostaglandin biosynthesis through inhibition of cyclooxygenase (COX) which exists as two isoforms (COX-1 and COX-2). NSAID-induced gastrointestinal toxicity is generally believed to occur through blockade of COX-1 activity, whereas the anti-inflammatory effects of NSAIDs are thought to occur primarily through inhibition of the inducible isoform, COX-2. However, the situation in the kidney may be somewhat different. Recent studies have demonstrated that COX-2 is constitutively expressed in renal tissues of all species; this isoform may, therefore, be intimately involved in prostaglandin-dependent renal homeostatic processes. Drugs that selectively inhibit COX-2 might, therefore, be expected to produce effects on renal function similar to nonselective NSAIDs which inhibit both COX-1 and COX-2. This assertion is borne out by recent clinical studies showing that the COX-2 inhibitors rofecoxib and celecoxib procedure qualitative changes in urinary prostaglandin excretion, glomerular filtration rate, sodium retention, and their consequences similar to nonselective NSAIDs. It, therefore, seems unlikely that these COX-2 inhibitors (and perhaps their successors) will offer renal safety benefits over nonselective NSAID therapies, and, at this juncture, it is reasonable to assume that all NSAIDs, including COX-2-selective inhibitors, share a similar risk for adverse renal effects.

          Related collections

          Most cited references 11

          • Record: found
          • Abstract: found
          • Article: not found

          Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group.

          Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis. We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers). Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001). The respective rates of complicated confirmed events (perforation, obstruction, and severe upper gastrointestinal bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (relative risk, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.005). The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups. In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Gastrointestinal Toxicity With Celecoxib vs Nonsteroidal Anti-inflammatory Drugs for Osteoarthritis and Rheumatoid Arthritis

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration.

              Cyclooxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis and the target enzymes for the widely used nonsteroidal anti-inflammatory drugs. To study the physiological roles of the individual isoforms, we have disrupted the mouse Ptgs1 gene encoding COX-1. Homozygous Ptgs1 mutant mice survive well, have no gastric pathology, and show less indomethacin-induced gastric ulceration than wild-type mice, even though their gastric prostaglandin E2 levels are about 1% of wild type. The homozygous mutant mice have reduced platelet aggregation and a decreased inflammatory response to arachidonic acid, but not to tetradecanoyl phorbol acetate. Ptgs1 homozygous mutant females mated to homozygous mutant males produce few live offspring. COX-1-deficient mice provide a useful model to distinguish the physiological roles of COX-1 and COX-2.
                Bookmark

                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2001
                February 2001
                12 March 2001
                : 21
                : 1
                : 1-15
                Affiliations
                aDepartment of Medicine, Indiana University School of Medicine, Indianapolis, Ind., and bMerck & Co., Inc., Rahway, N.J., USA
                Article
                46212 Am J Nephrol 2001;21:1–15
                10.1159/000046212
                11275626
                © 2001 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 9, Tables: 3, References: 81, Pages: 15
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/46212
                Categories
                Editorial Review

                Comments

                Comment on this article

                Similar content 567

                Cited by 14