Selective COX-2 Inhibitors

Pharmacology, Clinical Effects and Therapeutic Potential

  • John Vane
  • Jack Botting

Table of contents

  1. Front Matter
    Pages i-ix
  2. M. Pairet, J. Van Ryn, A. Mauz, H. Schierok, W. Diederen, D. Türck et al.
    Pages 27-46
  3. N. G. Bazan, V. L. Marcheselli, P. K. Mukherjee, W. J. Lukiw, W. C. Gordon, D. Zhang
    Pages 47-53
  4. D. L. Simmons, M. L. Madsen, P. M. Robertson
    Pages 55-65
  5. R. N. Dubois, H. Sheng, J. Shao, C. Williams, R. D. Beauchamp
    Pages 67-72
  6. C. Patrono, F. Cipollone, G. Renda, P. Patrignani
    Pages 73-78
  7. C. J. Hawkey
    Pages 79-85
  8. J. C. Frölich, D. O. Stichtenoth
    Pages 87-98
  9. R. J. Gryglewski
    Pages 99-107
  10. A. W. Ford-Hutchinson
    Pages 117-125
  11. P. Isakson, B. Zweifel, J. Masferrer, C. Koboldt, K. Seibert, R. Hubbard et al.
    Pages 127-133
  12. Back Matter
    Pages 145-150

About this book

Introduction

The mainstay of therapy for rheumatoid disease is the non-steroid antiinflammatory drugs (NSAIDs), despite their inherent gastrointestinal toxicity and ability to cause renal damage in susceptible patients. The theory that the beneficial and toxic effects of NSAIDs stem from a reduction in prostanoid production through inhibition of cyclooxygenase implied that particular toxicities were inevitable with NSAIDs and would always be correlated with efficacy. However, over the years, it became apparent that at therapeutic doses, some NSAIDs had greater toxic side-effects than others, a fact not explained by the general theory. A significant clarification arose from the discovery that there are two distinct isoforms of COX, a constitutive enzyme (COX-I) responsible for the production of prostanoids necessary for platelet aggregation and protection of the gastric mucosa and kidney; and an inducible enzyme (COX-2) that is newly synthesized at sites of tissue damage and produces prostaglandins that manifest pathological effects. It became clear that different NSAIDs had greater or lesser effects on COX-I when used in therapeutic doses, explaining the variation in side-effects. ' The elucidation of the crystal structure of these different enzymes and the skills of medicinal chemists have led to the synthesis of new chemicals with a selectivity for the inducible enzyme, and thus with therapeutic efficacy without those toxic effects result­ ing from inhibition of the constitutive enzyme.

Keywords

apoptosis asthma brain cell cell death classification death drugs enzymes inflammation research retina tumor tumorigenesis vascular disease

Editors and affiliations

  • John Vane
    • 1
  • Jack Botting
    • 1
  1. 1.The William Harvey Research InstituteSaint Bartholomew’s and the Royal London School of Medicine and DentistryLondonUK

Bibliographic information

  • DOI https://doi.org/10.1007/978-94-011-4872-6
  • Copyright Information Kluwer Academic Publishers and William Harvey Press 1998
  • Publisher Name Springer, Dordrecht
  • eBook Packages Springer Book Archive
  • Print ISBN 978-94-010-6041-7
  • Online ISBN 978-94-011-4872-6
  • About this book
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