Cox 2 Inhibitor Research

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.

Cox-2 Inhibitors are newly developed drugs for inflammation that selectively block the Cox-2 enzyme. Blocking this enzyme impedes the production of the chemical messengers (prostaglandins) that cause the pain and swelling of arthritis inflammation. Cox-2 inhibitors are a new class of non-steroidal anti-inflammatory drugs (NSAIDS). Because they selectively block the Cox-2 enzyme and not the Cox-1 enzyme, these drugs are uniquely different from traditional NSAIDS. This book explores new research in the field.

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.

COX-2 Inhibitors are newly developed drugs for inflammation that selectively block the COX-2 enzyme. Blocking this enzyme impedes the production of the chemical messengers (prostaglandins) that cause the pain and swelling of arthritis inflammation. Cox-2 inhibitors are a new class of nonsteroidal anti-inflammatory drugs (NSAIDS). Because they selectively block the Cox-2 enzyme and not the Cox-1 enzyme, these drugs are uniquely different from traditional NSAIDS. This book explores new research in this field.

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.

The first thorough review of cyclooxygenase inhibitors, including their toxicity mechanisms and toxicopathological risks Cyclooxygenases (COXs) are enzymes responsible for the formation of an important class of biological mediators called prostanoids. Prostanoids such as prostaglandins mediate inflammatory and anaphylactic reactions. For those suffering from inflammation and pain, the pharmacological inhibition of COXs, with non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, can provide relief. Yet the use of NSAIDs can trigger toxicological effects as well, leading to potential health risks. Comparative Pathophysiology and Toxicology of Cyclooxygenases provides a comprehensive overview of how COX inhibitors affect various bodily systems, specifically the toxicity mechanisms triggered when the COX enzyme is inhibited. The book provides an introduction to the discovery of cyclooxygenases, their use as therapeutic agents, as well as an historical perspective. Shedding light on the differences in expression, pathophysiology, and toxicology of COX inhibitors across species, the book offers a systematic examination of the effects and pathophysiology of COX inhibitors and their mechanisms of toxicity, beginning with the GI tract. Subsequent chapters cover: The pathophysiology of COX inhibition on bone, tendon, and ligament healing COX inhibitors and renal system pathophysiology and mechanisms of toxicity The pathophysiologic role of COX inhibition in the ocular system COX inhibition and the respiratory and cardiovascular systems The book also sheds light on the latest research devoted to developing COX inhibitors with no adverse side-effects. The first book to offer a thorough comparative look at the toxicological effects of COX inhibitors throughout the body, this invaluable resource will help advance the research and development of safer and more effective COX drugs.

Cox-2 Inhibitors: Advances in Research and Application: 2011 Edition is a ScholarlyPaper™ that delivers timely, authoritative, and intensively focused information about Cox-2 Inhibitors in a compact format. The editors have built Cox-2 Inhibitors: Advances in Research and Application: 2011 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Cox-2 Inhibitors in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Cox-2 Inhibitors: Advances in Research and Application: 2011 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.

Cox-2 Inhibitors—Advances in Research and Application: 2012 Edition is a ScholarlyBrief™ that delivers timely, authoritative, comprehensive, and specialized information about Cox-2 Inhibitors in a concise format. The editors have built Cox-2 Inhibitors—Advances in Research and Application: 2012 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Cox-2 Inhibitors in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Cox-2 Inhibitors—Advances in Research and Application: 2012 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.