Selective COX-2 Inhibitors

Pharmacology, Clinical Effects and Therapeutic Potential

Editors: Vane, Sir John R., Botting, Jack (Eds.)

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About this book

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.

About the authors

Sir John Vane is the Director General at the William Harvey Research Institute, an independent charitable foundation within Queen Mary and Westfield College of the University of London, UK.
Sir John Vane shared the Nobel Prize in Physiology or Medicine in 1982 for his discoveries of the mechanism of action of aspirin and of prostacyclin, as well as his work on other prostanoids. Jack Botting is Consultant at the William Harvey Research Institute, an independent charitable foundation within Queen Mary and Westfield College of the University of London, UK.

Table of contents (14 chapters)

Table of contents (14 chapters)
  • Mechanism of action of anti-inflammatory drugs: an overview

    Vane, J. R. (et al.)

    Pages 1-17

  • The structure of human cyclooxygenase-2 and selective inhibitors

    Browner, M. F.

    Pages 19-26

  • Differential inhibition of COX-1 and COX-2 by NSAIDs: a summary of results obtained using various test systems

    Pairet, M. (et al.)

    Pages 27-46

  • COX-2 in brain and retina: role in neuronal survival

    Bazan, N. G. (et al.)

    Pages 47-53

  • COX-2 and apoptosis: NSAIDs as effectors of programmed cell death

    Simmons, D. L. (et al.)

    Pages 55-65

Buy this book

eBook $109.00
price for USA in USD (gross)
  • ISBN 978-94-011-4872-6
  • Digitally watermarked, DRM-free
  • Included format: PDF
  • ebooks can be used on all reading devices
  • Immediate eBook download after purchase
Softcover $139.00
price for USA in USD
  • ISBN 978-94-010-6041-7
  • Free shipping for individuals worldwide
  • Usually dispatched within 3 to 5 business days.
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Bibliographic Information

Bibliographic Information
Book Title
Selective COX-2 Inhibitors
Book Subtitle
Pharmacology, Clinical Effects and Therapeutic Potential
Editors
  • Sir John R. Vane
  • Jack Botting
Copyright
1998
Publisher
Springer Netherlands
Copyright Holder
Springer Science+Business Media Dordrecht
eBook ISBN
978-94-011-4872-6
DOI
10.1007/978-94-011-4872-6
Softcover ISBN
978-94-010-6041-7
Edition Number
1
Number of Pages
IX, 150
Topics