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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.
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.
The Essence of Analgesia and Analgesics is an invaluable practical resource for clinicians giving pain relief in any clinical setting, describing the pharmacologic principles and clinical use of all available pain medications. As well as detailed overviews of pain processing and analgesic theory, sections are dedicated to oral and panteral opioid analgesics, neuraxial opioids, NSAIDs, local anesthetics, anticonvulsant type analgesics, NMDA antagonists, alpha adrenergic analgesics, antidepressant analgesics, muscle relaxants, adjuvant medications, and new and emerging analgesics. The concise format of the chapters allows for quick and easy reading and assimilation of information. Enhanced by summary tables and figures, each chapter provides an overview of a particular drug, covering chemical structure, mode of activity, indications, contraindications, common doses and uses, advantages and disadvantages, and drug related adverse events. Key references are also provided. Edited by leading experts in pain management, this is essential reading for any clinician involved in pain management.
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.
This book covers all the pharmacology you need, from basic science pharmacology and pathophysiology, through to clinical pharmacology to therapeutics, in line with the integrated approach of new medical curricula. The first section covers the basic principles, and the rest is organised by body systems. The book ends with sections on toxicity and prescribing practice. Integrates basic science pharmacology, clinical pharmacology and therapeutics Brief review of pathophysiology of major diseases Case histories and multiple choice questions (and answers) Tabular presentation of all common drugs within each class Section on further reading Kinetics chapter simplified with more practical examples Includes more on genetic issues Drug tables made more concise to make information more accessible Fully updated to reflect current clinical practice
The clinical practice of anesthesia has undergone many advances in the past few years, making this the perfect time for a new state-of-the-art anesthesia textbook for practitioners and trainees. The goal of this book is to provide a modern, clinically focused textbook giving rapid access to comprehensive, succinct knowledge from experts in the field. All clinical topics of relevance to anesthesiology are organized into 29 sections consisting of more than 180 chapters. The print version contains 166 chapters that cover all of the essential clinical topics, while an additional 17 chapters on subjects of interest to the more advanced practitioner can be freely accessed at www.cambridge.org/vacanti. Newer techniques such as ultrasound nerve blocks, robotic surgery and transesophageal echocardiography are included, and numerous illustrations and tables assist the reader in rapidly assimilating key information. This authoritative text is edited by distinguished Harvard Medical School faculty, with contributors from many of the leading academic anesthesiology departments in the United States and an introduction from Dr S. R. Mallampati. This book is your essential companion when preparing for board review and recertification exams and in your daily clinical practice.
Logically organized and easy to use, Drugs for Pregnant and Lactating Women, 3rd Edition, is your #1 resource for details on how virtually all of today’s drugs and herbal supplements interact with pregnancy and lactation. More than just a dosing manual, this unique title by Dr. Carl P. Weiner fully explains whether each drug is FDA-approved for use by expecting or nursing mothers, is known to be safe for use, or is known to pose a danger. With up-to-date coverage of nearly 2,000 substances, it provides the thorough details you need to choose the most effective course of treatment. Uses a consistent, easy-to-follow format for each substance: generic and trade name • class • indications • mechanism of action • dosage, with contraindications and cautions • maternal considerations • fetal considerations • drug interactions • breastfeeding safety • references • and summary information. Describes over-the-counter drugs and alternative medications as well as prescription drugs. Uses an eye-catching icon to highlight known teratogens. Includes international drug names to give this reference a global perspective. Features new letter thumb tabs for easier navigation. Includes dozens of new drugs and thorough updates throughout.
No matter what questions arise in practice or while preparing for boards, Pain Management Secrets, 3rd Edition has the answers. A two-color page layout, portable size, and a list of the “Top 100 Secrets in pain management help you better meet the challenges you face today. You’ll find all the features you rely on from the Secrets Series®—a question-and-answer format, lists, mnemonics, tables and an informal tone—that make reference fast and easy. Expedites reference and review with a question-and-answer format, bulleted lists, mnemonics, and practical tips from the authors. Features a two-color page layout, "Key Points" boxes, and lists of useful web sites to enhance your reference power. Presents a chapter containing "Top 100 Secrets", providing you with an overview of essential material for last-minute study or self-assessment. Fits comfortably in the pocket of your lab coat so you have it conveniently on hand at all times. Features new editors, Charles E. Argoff, MD and Gary McCleane, MD who present a thorough update on the latest in pain management. Presents a new contemporary internal design that helps you navigate the text easier.
This textbook provides an overview of pain management useful to specialists as well as non-specialists, surgeons, and nursing staff.