Antiarrhythmic Drugs: Mechanisms of Antiarrhythmic and Proarrhythmic Actions

ISBN-13: 9783642856266 / Angielski / Miękka / 2012 / 410 str.

Gunter Breithardt;G. Hindricks;John a. Camm

Opis

The past 10 years have seen a remarkable change in the approach to cardiac arrhythmias, from a position of confidence and a feeling of well-being about pharmacological treatment to a situation in which there is now marked uncertainty and general apprehension about the role of antiarrhythmic drugs. Until relatively recently the prevailing concept in antiarrhythmic therapy was that arrhythmias could be controlled by drugs which slowed conduction or suppressed automaticity, goals well served by the sodium channel-blocking drugs and glycosides. Drug re search was based largely on the development of agents mimicking those already available, but with greater efficacy, fewer side effects or a more favourable phar macokinetic profile. The CAST trial stands out as a landmark in the evolution of arrhytmia manage ment; rarely has a single trial had such a profound impact not only on clinical prac tice, but also on the whole approach of those involved in the research, development and regulation of antiarrhythmic drugs. The results of the CAST trial, designed to redress the shortcomings of earlier trials which had failed to demonstrate the anticipated improvement in mortality post-myocardial infarction with the use of class I agents, are well known. The CAST and CAST II showed an increase in mor tality associated with the active agent (encainide, flecainide or morizicine) com pared to placebo treatment. They firmly established the potential danger in the use of class I drugs."

Spis treści

Basic Mechanisms of Antiarrhythmic Drug Action.- Sodium Channel Blockade as an Antiarrhythmic Mechanism.- Pharmacology of T and L type Ca2+ Channels in Cardiac Tissue.- Molecular Biology and Ion Channel Biophysics: Their Role in Rational Pharmacological Antiarrhythmic Therapy.- Selective Pharmacological Modification of Repolarizing Currents: Antiarrhythmic and Proarrhythmic Actions of Agents that Influence Repolarization of the Heart.- A Shift from Class to Class III Drugs in the Medical Treatment of Arrhythmias: Wishful Thinking?.- Use Dependence and Reverse Use Dependence of Antiarrhythmic Agents: Pro-and Antiarrhythmic Actions.- Modulation of Antiarrhythmic Drug Action by Disease and Injury.- Interaction of Transient Ischemia with Antiarrhythmic Drugs.- Management of Patients with Sustained Ventricular Tachyarrhythmias: Differnt Clinical Studies, Different Patients.- Antiarrhythmic Drug Action: Modulation by Disease and Injury.- Reentrant Excitation: Pharmacological Interactions.- Pharmacological Modulation of Reentrant Excitation in Experimental Models.- Reentry in Clinical Arrhythmias: Mechanisms Responsible for Antiarrhythmic Drug Efficacy.- Variability of the Arrhythmogenic Substrate: Drug Influences.- Experimental Models for the Assessment of Antiarrhythmic and Proarrhythmic Drug Action: Traditional and Newer Models.- Influence of the Autonomic Nervous System on the Action of Antiarrhythmic Drugs.- Role of Drugs in Torsade de Pointes and Triggered Activity.- The Study of Pharmacokinetics and Pharmacodynamics as a Tool for Understanding Mechanisms of Antiarrhythmic Drug Action.- Electrophysiologic Effects, Clinical Efficacy and Antiarrhythmic and Proarrhythmic Effects of Sodium Channel Blockers in Patients with Ventricular Tachyarrhythmias.- Antiarrhythmic Versus Proarrhythmic Effects of Class III Agents.- “Novel” Antiarrhythmic Drugs.- Electrophysiologic Properties and Antiarrhythmic Effects of Adenosine and Adenosine Triphosphate.- Magnesium-Electrophysiological Effects, Antiarrhythmic Properties and Clinical Applications.- Future Perspectives.- The Classification of Antiarrhythmic Drugs: How do we Educate the Scientist and the Clinician?.

Blurb

Management and prevention of tachyarrhythmias, especially of serious ventricular arrhythmias after myocardial infarction, is still a major problem. Large-scale evidence suggests an increased harm induced by antiarrhythmic drugs in the presence of organic heart disease although they effectively suppress spontaneous arrhythmias. This increased risk has been linked to their proarrhythmic potential and to possible interactions by ischaemia. However, the mechanisms by which antiarrhythmic drugs exert their antiarrhythmic and proarrhythmic actions are still poorly understood. Therefore, it was a time to present an update on the mechanisms of antiarrhythmic and proarrhythmic action of drugs which act on the electrophysiological properties of the heart. World renowned electrophysiologists as well as clinicians have joint to address important topics which range from the effect of antiarrhythmic drugs on single channels and on arrhythmia models to the clinical arena.