What niche will newer class III antiarrhythmic drugs occupy?

Singh, Bramah N.; Sarma, J. S. M.

doi:10.1007/s11886-001-0086-x

Cited by 10 publications

(3 citation statements)

References 37 publications

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“…Such compounds may be the result of the block of a single repolarizing ionic current (eg, dofetilide) or multiple currents (ibutilide, tedisamil, or azimilide). They are of particular value in atrial fibrillation and flutter as judged by the properties of dofetilide, ibutilide, and azimilide [49]. Under certain clinical circumstances, they may have advantages over complex compounds such as sotalol or amiodarone.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of antiarrhythmic drug actions and their clinical relevance for controlling disorders of cardiac rhythm

Srivatsa

Wadhani²,

Singh³

2002

Curr Cardiol Rep

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This review on antiarrhythmic drugs traces the evolution of the fundamental mechanisms of action of drugs that have been used to control disorders of cardiac rhythm. It describes the very earliest data from experimental studies that dealt with the effects of acute and chronic administration of drugs in whole animals combined with the measurements of the action potential duration and the effective refractory period in isolated tissues. Antiarrhythmic drugs were found to have properties consistent with the block of fast sodium channel conduction, adrenergic blockade, repolarization block, and the block of slow-channel mediated conduction especially in the atrioventricular node. Over the past 15 years, the attention has focused on atrial tissue with atrial fibrillation emerging as the most common arrhythmia in clinical practice. Drug-induced increases in refractoriness as a function rate and in wavelength (product of refractoriness and conduction velocity), and a reduction in numbers of wavelets have been found to be critical in the conversion of atrial fibrillation and maintenance of sinus rhythm. The continued development of newer pharmacologic agents is likely to lead to the resolution of the controversy regarding rhythm versus rate control in various clinical subsets of the arrhythmia by controlled clinical trials.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of antiarrhythmic drug actions and their clinical relevance for controlling disorders of cardiac rhythm

Srivatsa

Wadhani²,

Singh³

2002

Curr Cardiol Rep

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“…Despite the marked effectiveness of amiodarone and sotalol in clinical trials, drug development continued with numerous other pure class III agents. These drugs are highly potent, channel-selective blockers and include dofetilide, ibutilide, and azimilide [Colatsky and Follmer, 1989;Katritsis and Camm, 1993;Hondeghem, 1994;Singh and Sarma, 2001]. These agents have antifibrillatory effects in atrial fibrillation and flutter and in ventricular tachyarrhythmias.…”

Section: Antiarrhythmic Drug Development Shifts From Class I To Classmentioning

confidence: 99%

Antiarrhythmic drug development: Historical review and future perspective

Pugsley

2002

Drug Development Research

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Cardiac ion channels represent the traditional target for antiarrhythmic drug development. Although channel-selective drugs are effective in treating supraventricular arrhythmias, they are less effective against life-threatening ventricular arrhythmias, and some are proarrhythmic. Paradoxically, the one exception, amiodarone, which uniquely suppresses ventricular fibrillation without proarrhythmia, is one of the least channel-selective drugs currently available (and thus has extracardiac side effects). Thus, antiarrhythmic drug development has become becalmed. This review describes the history of antiarrhythmic drug development, considers antiarrhythmic drugs to date, and provides an overview of current novel therapeutic areas of drug development in an attempt to introduce some of the articles contained within this focused issue of Drug Development Research. Models (for preclinical antiarrhythmic drug assessment) and mechanisms (of drug action and arrhythmia suppression) are the themes of this issue. Drug Dev. Res. 55:3-16, 2002 ION CHANNEL BLOCKADE-THE FUNDAMENTAL PROPERTY FOR ANTIARRHYTHMIC DRUG DEVELOPMENTThe models of ion channel blockade currently used to quantify and qualify the actions of antiarrhythmic drugs in cardiac tissue under ischaemic or normal conditions are based on many key observations accumulated over decades of basic and clinical research. Distinctions between the activity of many different drugs are based primarily on differences in the electrophysiological properties in tissues subjected to the two conditions. Early development of models of drug-mediated ion channel blockade focused on neuronal, rather than cardiac, tissue. However, most findings in neurons have been applied to, and accurately describe, drug actions in the heart. Hodgkin and Huxley [1952] first examined the electrical properties of the sodium current using the squid giant axon. The results of this work provided the first implicit model for ion channel function whereby the sodium channel may exist in three states: resting (closed), active (open), and closed (inactive). These channel states are a function of voltage and time and are dependent on membrane potential. Hodgkin and Huxley investigated the kinetics of activation and inactivation of this channel and proposed that these properties were caused by "m" and "h" gates, respectively. Around this same time, Weidmann [1955] found that in the presence of antiarrhythmic drugs (sodium channel blockers including quinidine, procainamide, and diphenhydramine) the voltage-dependence of the maximum rate of depolarization (V max ) was shifted to more negative potentials. Weidmann suggested that this was caused by drug interaction with the inactivation (h) gate (according to Hodgkin and Huxley formalism) of the sodium channel. These studies provided the fundamental tenets for the development of antiarrhythmic drug theory that exists today. Antiarrhythmic drug development by basic researchers was then augmented by clinicians who concurrently determined a medical usefulness ...

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“…Furthermore, pharmacologic therapy remains the mainstay of control and prevention of atrial fibrillation (2,3,8). No recent spectacular advances have been made in the synthesis and characterization of novel antiarrhythmic and antifibrillatory compounds (9)(10)(11)(12)(13)(14)(15). However, can we learn some lessons from the study of existing drugs and their effects in atrial fibrillation?…”

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confidence: 99%

Atrial Fibrillation Following Investigation of Rhythm Management: AFFIRM Trial Outcomes. What Might Be Their Implications for Arrhythmia Control?

Singh

2002

J Cardiovasc Pharmacol Ther

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During the last decade or so, major changes have been made in the approaches to the control of supraventricular as well as ventricular tachyarrhythmias. A few landmarks need emphasis. A precise understanding of the mechanisms of the origin of cardiac arrhythmias led to the development of electrode catheter ablative techniques; these developments have resulted in an extraordinary high degree of success in curing a very large proportion of patients with re-entrant supraventricular arrhythmias. This striking degree of success, however, has been essentially elusive in the case of ventricular tachyarrhythmias, where the development and refinement of the implantable cardioverter defibrillator has substantially altered the therapeutic landscape of these life-threatening arrhythmias (1).Although they prolong survival in many patients, these important techniques and approaches have not made major inroads in the management of certain arrhythmias and, in particular, atrial fibrillation (2-5). Despite the rapid advances made in understanding how this arrhythmia arises, and how it is propagated and perpetuated (6,7), its treatment remains frustrating and undoubtedly challenging. Furthermore, pharmacologic therapy remains the mainstay of control and prevention of atrial fibrillation (2,3,8). No recent spectacular advances have been made in the synthesis and characterization of novel antiarrhythmic and antifibrillatory compounds (9-15). However, can we learn some lessons from the study of existing drugs and their effects in atrial fibrillation?

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What niche will newer class III antiarrhythmic drugs occupy?

Cited by 10 publications

References 37 publications

Mechanisms of antiarrhythmic drug actions and their clinical relevance for controlling disorders of cardiac rhythm

Mechanisms of antiarrhythmic drug actions and their clinical relevance for controlling disorders of cardiac rhythm

Antiarrhythmic drug development: Historical review and future perspective

Atrial Fibrillation Following Investigation of Rhythm Management: AFFIRM Trial Outcomes. What Might Be Their Implications for Arrhythmia Control?

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