Download or read book Small Molecule Targeting of Cardiac HERG Channels to Protect Against Arrhythmias written by Ravichandra Venkateshappa and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The hERG potassium channel encoded by the ether-a-go-go-related gene (hERG) is essential for ventricular repolarization. These channels have a distinctive kinetic profile in that they conduct a modest current during the plateau phase, attain their maximum conductance during phase 3 of cardiac repolarization, and then close slowly. Due to acquired or hereditary conditions, dysfunction of these channels reduces hERG currents, prolongs action potential length (as shown by a prolonged QT interval), and predisposes individuals to potentially fatal ventricular arrhythmias. This-relationship between hERG dysfunction and QT prolongation (Long QT Syndrome, LQTS) has sparked interest in the role of hERG channels in phase 3 repolarization and arrhythmia generation and the possibility that small molecules hERG agonists may be utilized to restore function. A series of small molecules have been found and classified according to their mode of action. In -vitro and in -vivo investigations have shown that Type 2 activators that enhance hERG currents by decreasing channel inactivation, risk over-correction of the action potential and Short QT Syndrome. Type 1 activators, which preferentially slow the deactivation of hERG channels, on the other hand, may provide a more subtle restoration of hERG currents. A few studies have postulated that the slow deactivation of hERG channels may suppress triggered activity by allowing protective repolarizing current flow in response to premature depolarizations arriving in the refractory period. However, there are no direct experimental correlations between these protective hERG currents and ventricular arrhythmia, or the effects of manipulation of deactivation by Type 1 hERG activators. In my thesis, I examine the role of hERG protective currents and the use of a hERG Type 1 activator as a mechanism based therapy for both acquired and inherited forms of LQTS. Using a translational approach ranging in complexity from single cells to the entire organ these studies aim to provide improved understanding of the pathogenic mechanisms associated with hERG channel dysfunction and the effect of targeted slowing of hERG deactivation in suppressing arrhythmias.
Download or read book Anesthetic Pharmacology written by Alex S. Evers and published by Cambridge University Press. This book was released on 2011-03-10 with total page 2902 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years our understanding of molecular mechanisms of drug action and interindividual variability in drug response has grown enormously. Meanwhile, the practice of anesthesiology has expanded to the preoperative environment and numerous locations outside the OR. Anesthetic Pharmacology: Basic Principles and Clinical Practice, 2nd edition, is an outstanding therapeutic resource in anesthesia and critical care: Section 1 introduces the principles of drug action, Section 2 presents the molecular, cellular and integrated physiology of the target organ/functional system and Section 3 reviews the pharmacology and toxicology of anesthetic drugs. The new Section 4, Therapeutics of Clinical Practice, provides integrated and comparative pharmacology and the practical application of drugs in daily clinical practice. Edited by three highly acclaimed academic anesthetic pharmacologists, with contributions from an international team of experts, and illustrated in full colour, this is a sophisticated, user-friendly resource for all practitioners providing care in the perioperative period.
Download or read book Myocardial Repolarization From Gene to Bedside written by Ali Oto and published by Wiley-Blackwell. This book was released on 2001-12-10 with total page 402 pages. Available in PDF, EPUB and Kindle. Book excerpt: A convenient guide of easily accessible information on the mechanisms of myocardial repolarization and related clinical issues. This book provides a unique collection of contributions by prominent cardiologists on the current knowledge of the mechanisms of arrhythmias, the molecular and genetic bases of noninvasive electrocardiologic diagnosis, and other related clinical issues. In addition to mechanistic aspects, recent developments in the diagnosis of arrhythmias using newly recognized markers (QT dispersion, T-wave alternans, etc.) and their clinical importance are addressed in an easily accessible manner by world-renowned authors. The book is a quick-reference for practicing cardiologists and electrophysiologists, those in training, and others who work in the field of arrhythmology.
Download or read book Principles of Safety Pharmacology written by Michael K. Pugsley and published by Springer. This book was released on 2015-06-19 with total page 477 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book illustrates, in a comprehensive manner, the most current areas of importance to Safety Pharmacology, a burgeoning unique pharmacological discipline with important ties to academia, industry and regulatory authorities. It provides readers with a definitive collection of topics containing essential information on the latest industry guidelines and overviews current and breakthrough topics in both functional and molecular pharmacology. An additional novelty of the book is that it constitutes academic, pharmaceutical and biotechnology perspectives for Safety Pharmacology issues. Each chapter is written by an expert in the area and includes not only a fundamental background regarding the topic but also detailed descriptions of currently accepted, validated models and methods as well as innovative methodologies used in drug discovery.
Download or read book Ion Channels as Targets in Drug Discovery written by Gary Stephens and published by Springer Nature. This book was released on with total page 540 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Polypharmacology in Drug Discovery written by Jens-Uwe Peters and published by John Wiley & Sons. This book was released on 2012-03-13 with total page 542 pages. Available in PDF, EPUB and Kindle. Book excerpt: An essential outline of the main facets of polypharmacology in drug discovery research Extending drug discovery opportunities beyond the "one drug, one target" philosophy, a polypharmacological approach to the treatment of complex diseases is emerging as a hot topic in both industry and academic research. Polypharmacology in Drug Discovery presents an overview of the various facets of polypharmacology and how it can be applied as an innovative concept for developing medicines for treating bacterial infections, epilepsy, cancer, psychiatric disorders, and more. Filled with a collection of instructive case studies that reinforce the material and illuminate the subject, this practical guide: Covers the two-sided nature of polypharmacology—its contribution to adverse drug reactions and its benefit in certain therapeutic drug classes Addresses the important topic of polypharmacology in drug discovery, a subject that has not been thoroughly covered outside of scattered journal articles Overviews state-of-the-art approaches and developments to help readers understand concepts and issues related to polypharmacology Fosters interdisciplinary drug discovery research by embracing computational, synthetic, in vitro and in vivo pharmacological and clinical aspects of polypharmacology A clear road map for helping readers successfully navigate around the problems involved with promiscuous ligands and targets, Polypharmacology in Drug Discovery provides real examples, in-depth explanations and discussions, and detailed reviews and opinions to spark inspiration for new drug discovery projects.
Download or read book Antitargets and Drug Safety written by Laszlo Urban and published by John Wiley & Sons. This book was released on 2015-06-08 with total page 524 pages. Available in PDF, EPUB and Kindle. Book excerpt: With its focus on emerging concerns of kinase and GPCR-mediated antitarget effects, this vital reference for drug developers addresses one of the hot topics in drug safety now and in future. Divided into three major parts, the first section deals with novel technologies and includes the utility of adverse event reports to drug discovery, the translational aspects of preclinical safety findings, broader computational prediction of drug side-effects, and a description of the serotonergic system. The main part of the book looks at some of the most common antitarget-mediated side effects, focusing on hepatotoxicity in drug safety, cardiovascular toxicity and signaling effects via kinase and GPCR anti-targets. In the final section, several case studies of recently developed drugs illustrate how to prevent anti-target effects and how big pharma deals with them if they occur. The more recent field of systems pharmacology has gained prominence and this is reflected in chapters dedicated to the utility in deciphering and modeling anti-targets. The final chapter is concerned with those compounds that inadvertently elicit CNS mediated adverse events, including a pragmatic description of ways to mitigate these types of safety risks. Written as a companion to the successful book on antitargets by Vaz and Klabunde, this new volume focuses on recent progress and new classes, methods and case studies that were not previously covered.
Download or read book Molecular Basis of Cardiovascular Disease written by Kenneth R. Chien and published by . This book was released on 2004 with total page 760 pages. Available in PDF, EPUB and Kindle. Book excerpt: The 2nd Edition of this heralded companion to Braunwald's Heart Disease explores the molecular mechanisms of cardiology and the scientific advances that are changing the practice of cardiology today. International experts discuss the role of genetics in cardiovascular disease the molecular basis of ischemic disease, thrombosis and hypertension genetic mapping approaches to inherited disorders biologically targeted agents for hypertension and heart failure and much more. Abundant figures and tables illustrate key concepts. Addresses most common cardiovascular problems from a molecular standpoint. Explores developing treatments for cardiovascular problems based on genetics. Provides references to Braunwald's Heart Disease, 6th Edition Examines today's cutting edge advances in molecular cardiology and the future of gene therapy, Examines the implications of cellular cholesterol metabolism in health and disease. . Delivers up-to-date information on understanding the origin of inherited disease.
Download or read book Cardiac Repolarization written by Ihor Gussak and published by Springer Science & Business Media. This book was released on 2003-03-13 with total page 549 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive review of all the latest developments in cardiac electrophysiology, focusing on both the clinical and experimental aspects of ventricular repolarization, including newly discovered clinical repolarization syndromes, electrocardiographic phenomena, and their correlation with the most recent advances in basic science. The authors illuminate the basic electrophysiologic, molecular, and pharmacologic mechanisms underlying ventricular repolarization, relate them to specific disease conditions, and examine the future of antiarrhythmic drug development based on both molecular and electrophysiological properties. They also fully review the clinical presentation and management of specific cardiac repolarization conditions.
Download or read book Pediatric Cardiology written by Alexander Sandor Nadas and published by W.B. Saunders Company. This book was released on 1972 with total page 776 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Cardiac Arrhythmias written by Ambrose S. Kibos and published by Springer Science & Business Media. This book was released on 2013-12-13 with total page 678 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers all the major aspects associated with pathophysiological development of cardiac arrhythmias (covering enhanced or suppressed automaticity, triggered activity, or re-entry), from basic concepts through disease association, limitations of current pharmacotherapy and implant therapies and on-going trials and analysis of new biomarkers based on current knowledge of cellular interaction and signalling. The book describes novel and state-of-the-art methods for differentiating between the major types of arrhythmia, structural abnormalities and current practice guidelines and determination of risk stratification associated with sudden cardiac death. A particular focus is on arrhythmias associated with atrial fibrillation and includes details of associations with cardiac disease, current detection, analysis and imaging and future perspectives.
Download or read book Accelerating the Development of Biomarkers for Drug Safety written by Institute of Medicine and published by National Academies Press. This book was released on 2009-07-20 with total page 101 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biomarkers can be defined as indicators of any biologic state, and they are central to the future of medicine. As the cost of developing drugs has risen in recent years, reducing the number of new drugs approved for use, biomarker development may be a way to cut costs, enhance safety, and provide a more focused and rational pathway to drug development. On October 24, 2008, the IOM's Forum on Drug Discovery, Development, and Translation held "Assessing and Accelerating Development of Biomarkers for Drug Safety," a one-day workshop, summarized in this volume, on the value of biomarkers in helping to determine drug safety during development.
Download or read book Drug Discovery and Evaluation Pharmacological Assays written by Hans Vogel and published by Springer Science & Business Media. This book was released on 2007-10-30 with total page 2118 pages. Available in PDF, EPUB and Kindle. Book excerpt: The new edition of this successful reference offers both cutting-edge and classic pharmacological methods. Thoroughly revised and expanded to two volumes, it offers an updated selection of the most frequently used assays for reliably detecting the pharmacological effects of potential drugs. Every chapter has been updated, and numerous assays have been added. Each of the more than 1,000 assays comprises a detailed protocol outlining purpose and rationale, and a critical assessment of the results and their pharmacological and clinical relevance.
Download or read book Ion Channel Diseases written by and published by Academic Press. This book was released on 2011-09-06 with total page 168 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ion channel dysfunction in humans leads to impairment of the excitable processes necessary for the normal function of several tissues, such as muscle and brain. It follows that an increasing number of human diseases have been associated with malfunctioning ion channels, many of which have a genetic component. This volume of Advances in Genetics presents a broad and comprehensive overview of the inherited channelopathies in humans, including clinical, genetic and molecular aspects of these conditions. Keeping true to the scope of the serial, novel genomic and modeling research approaches and a review of potential therapeutic approaches for each of these conditions are also incorporated.
Download or read book Genetic Programming III written by John R. Koza and published by Morgan Kaufmann. This book was released on 1999 with total page 1516 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic programming (GP) is a method for getting a computer to solve a problem by telling it what needs to be done instead of how to do it. Koza, Bennett, Andre, and Keane present genetically evolved solutions to dozens of problems of design, control, classification, system identification, and computational molecular biology. Among the solutions are 14 results competitive with human-produced results, including 10 rediscoveries of previously patented inventions.
Download or read book Ion Channel Drug Discovery written by Brian Cox and published by Royal Society of Chemistry. This book was released on 2014-09-03 with total page 385 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ion channel drug discovery is a rapidly evolving field fuelled by recent, but significant, advances in our understanding of ion channel function combined with enabling technologies such as automated electrophysiology. The resurgent interest in this target class by both pharmaceutical and academic scientists was clearly highlighted by the over-subscribed RSC/BPS 'Ion Channels as Therapeutic Targets' symposium in February 2009. This book builds on the platform created by that meeting, covering themes including advances in screening technology, ion channel structure and modelling and up-to-date case histories of the discovery of modulators of a range of channels, both voltage-gated and non-voltage-gated channels. The editors have built an extensive network of contacts in the field through their first-hand scientific experience, collaborations and conference participation and the organisation of the meeting at Novartis, Horsham, increased the network enabling the editors to draw on the experience of eminent researchers in the field. Interest and investment in ion channel modulation in both industrial and academic settings continues to grow as new therapeutic opportunities are identified and realised for ion channel modulation. This book provides a reference text by covering a combination of recent advances in the field, from technological and medicinal chemistry perspectives, as well as providing an introduction to the new 'ion channel drug discoverer'. The book has contributions from highly respected academic researchers, industrial researchers at the cutting edge of drug discovery and experts in enabling technology. This combination provides a complete picture of the field of interest to a wide range of readers.
Download or read book Encyclopedia of Heart Diseases written by M. Gabriel Khan and published by Elsevier. This book was released on 2005-12-14 with total page 678 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Encyclopedia of Heart Diseases is an accurate and reliable source of in-depth information on the diseases that kill more than 12 million individuals worldwide each year. In fact, cardiovascular diseases are more prevalent than the combined incidence of all forms of cancer, diabetes, asthma and leukemia. In one volume, this Encylopedia thoroughly covers these ailments and also includes in-depth analysis of less common and rare heart conditions to round out the volume's scope. Researchers, clinicians, and students alike will all find this resource an invaluable tool for quick reference before approaching the primary literature. * Coverage of more than 200 topics, including: applied pharmacology of current and experimental cardiac drugs, gene therapy, MRI, electron-beam CT, PET scan put in perspective, cardiac tests costs and justification, and new frontiers in cardiovascular research* More than 150 helpful figures and illustrations!* Dr. Khan is a well-published and respected expert in heart and heart diseases
