Author : Kelsey Constance Duggan
Publisher :
Page : 151 pages
File Size : 39,60 MB
Release : 2011
Category : Cyclooxygenase 2
ISBN :
Author : Sir John R. Vane
Publisher : Springer Science & Business Media
Page : 249 pages
File Size : 44,65 MB
Release : 2012-12-06
Category : Medical
ISBN : 9401090297
In 1971, Vane proposed that the mechanism of action of the aspirin-like drugs was through their inhibition of prostaglandin biosynthesis. Since then, there has been intense interest in the interaction between this diverse group of inhibitors and the enzyme known as cyclooxygenase (COX). It exists in two isoforms, COX-l and COX-2 (discovered some 5 years ago). Over the last two decades several new drugs have reached the market based on COX-l enzyme screens. Elucidation of the three-dimensional structure of COX-l has provided a new understanding for the actions of COX inhibitors. The constitutive isoform of COX, COX-l has clear physiological functions. Its activation leads, for instance, to the production of prostacyclin which when released by the endothelium is anti-thrombogenic and anti-atherosclerotic, and in the gastric mucosa is cyto protective. COX-l also generates prostaglandins in the kidney, where they help to maintain blood flow and promote natriuresis. The inducible isoform, COX-2, was discovered through its activity being increased in a number of cells by pro inflammatory stimuli. A year or so later, COX-2 was identified as a distinct isoform encoded by a different gene from COX-I. COX-2 is induced by inflammatory stimuli and by cytokines in migratory and other cells. Thus the anti-inflammatory actions of non-steroid anti-inflammatory drugs (NSAIDs) may be due to the inhibition of COX-2, whereas the unwanted side-effects such as irritation of the stomach lining and toxic effects on the kidney are due to inhibition of the constitutive enzyme, COX-I.
Author : Sir John R. Vane
Publisher : Springer Science & Business Media
Page : 153 pages
File Size : 47,19 MB
Release : 2012-12-06
Category : Medical
ISBN : 9401148724
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.
Author : Michel Pairet
Publisher : Springer Science & Business Media
Page : 264 pages
File Size : 12,7 MB
Release : 2004-03-29
Category : Medical
ISBN : 9783764369019
COX-2 inhibitors are important drugs with analgesic and anti-inflammatory effects. The discovery of COX-2, the evolution of drug development in this field and the implications of these developments in patient therapy are topics of this volume. This book presents both pre-clinical and clinical information and is important for clinicians interested in the latest information about this class of drugs, for researchers and for students in the field.
Author : Samir S. Ayoub
Publisher : Humana
Page : 218 pages
File Size : 42,52 MB
Release : 2016-08-23
Category : Medical
ISBN : 9781493956388
Since the discovery of the pharmacological and toxicological importance of inhibiting the cyclooxygenase (COX) enzymes by non-steroidal anti-inflammatory drugs (NSAIDs), much research has gone into the development of methods to study the biological functions of COX-1 and COX-2. In Cyclooxygenases: Methods and Protocols, experts and pioneers in the field present the most up-to-date in vitro and in vivo techniques routinely used in COX research. The volume delves into essential topics such as the purification, cloning, and expression of COX enzymes as well as in vitro assays aimed at determining the inhibitory potency of drugs on COX-1 and COX-2 activities, with chapters describing protocols used for the extraction and measurement of the prostanoids. This volume also describes in vivo disease models used to study the roles of COX-1 and COX-2 in gastrointestinal injury, inflammation, and pain. As a book in the highly successful Methods in Molecular BiologyTM series, the protocols chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Cyclooxygenases: Methods and Protocols serves as an indispensable tool for all scientists seeking the treatment of inflammation, pain, fever, and other harmful conditions.
Author : Ali Al-Kaf
Publisher : BoD – Books on Demand
Page : 163 pages
File Size : 20,49 MB
Release : 2017-08-23
Category : Medical
ISBN : 9535134434
This book intends to provide the reader with a comprehensive overview about the state of the art regarding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in physical and rehabilitation medicine and the study of the pharmacodynamics of existing and newly introduced NSAIDs in the management of pain and inflammation. It will also elaborate and refine already known knowledge on the mechanism(s) of nonsteroidal anti-inflammatory agents. This book may provide additional knowledge about the design and development of new drug delivery systems loaded with NSAIDs potentially useful in the treatment of chronic inflammatory-based diseases following circadian cycle, uses of NSAIDs as a source of medicinal plants, and the adverse effects and drug interactions of the nonsteroidal anti-inflammatory drugs.
Author :
Publisher : Birkhäuser
Page : 0 pages
File Size : 19,97 MB
Release : 2016-09-15
Category : Medical
ISBN : 9783764385309
Inflammation has become one of the most exciting and rewarding areas of medical research. Recent years have seen a revolution in our understanding of how blood and tissue cells interact and of the intracellular mechanisms controlling their activation. This has revealed the underlying inflammatory pathology of many diseases and provided multiple new targets for anti-inflammatory and immunomodulatory therapy. The Encyclopedia of Inflammatory Diseases will cover the following areas: Inflammatory Processes and Cells Inflammatory Diseases Mediators of Inflammation Pharmacology of Inflammation Since inflammatory diseases and their therapy cover a broad range of scientific and medical fields, the encyclopedia will be co-edited by four international experts, a clinician and three researchers from the disciplines of immunology, biochemistry, and pharmacology, in this way providing students, basic and clinical scientists and practitioners in academia, hospitals and industry with valuable interlinked information. This living project will serve as a reliable and comprehensive data pool for everybody working in inflammation research. Owing to its dynamic nature, it will grow with time and future editions, becoming an indispensible source of information for academia, clinical practitioners and industry.
Author : Raymond S. Sinatra
Publisher : Cambridge University Press
Page : 729 pages
File Size : 23,75 MB
Release : 2009-04-27
Category : Medical
ISBN : 0521874912
This textbook provides an overview of pain management useful to specialists as well as non-specialists, surgeons, and nursing staff.
Author : G.F. Gebhart
Publisher : Springer
Page : 0 pages
File Size : 22,82 MB
Release : 2013-11-18
Category : Medical
ISBN : 9783642287527
The Encyclopedia of Pain includes more than 3,000 entries and provides clear, detailed and up-to-date coverage of the current state of research, and treatment of pain. In addition, detailed essays provide in-depth information on all aspects of nociception and pain, including substrates, causes, pathophysiology, symptoms and signs, diagnoses and treatment. A thousand color figures enhance understanding of this too-little-understood topic. The book is available in print, in online only form, or in a print-online bundle.
Author : Pran Kishore Deb
Publisher :
Page : pages
File Size : 29,2 MB
Release : 2017
Category : Medicine
ISBN :
The nonsteroidal anti-inflammatory drugs (NSAIDs) are important class of therapeutic agents used for the treatment of pain, inflammation and fever. Nonselective inhibition of cyclooxygenase (COX-1 and COX-2) isoenzymes by classical NSAIDs is associated with undesirable side effects such as gastrointestinal (GI) and renal toxicities due to COX-1 inhibition. To circumvent this problem, several COX-2 selective inhibitors were developed with superior GI safety profile. However, the voluntary market withdrawal of potent COX-2 selective inhibitors (rofecoxib and valdecoxib) due to their severe cardiovascular toxicity which is also found to be associated with some of the traditional NSAIDs suggesting the need to relook into the entire class of NSAIDs rather than exclusively victimizing the COX-2 selective inhibitors. Furthermore, the recent evidences for the involvement of COX-2 selective inhibitors in the aetiology of many diseases, such as Alzheimer's disease, Parkinson's disease, diabetes, various cancers and so on, have gained much attention for researchers to design and develop novel COX-2 selective inhibitors with improved pharmacodynamics and pharmacokinetic profile. This chapter is focused on the detailed analysis of molecular basis of binding interactions of various NSAIDs by highlighting the role of crucial amino acid residues at the binding site of cyclooxygenase enzymes (COXs) to be considered for selective inhibition of COX-2 enzyme while emphasising the impact of significant CADD strategies employed for designing new potent COX-2 inhibitors with tuned selectivity.
