The arrhythmogenicity of antiarrhythmic agents (original) (raw)
1985, American Heart Journal
In the last decade the awareness of ventricular arrhythmias and the associated potential for sudden cardiac death has increased. Along with this changing perception, the technology by which these arrhythmias can be detected has also developed. This has led to the testing of new antiarrhythmic agents and to an increased use of the currently available drugs. Along with the increase in the use of antiarrhythmic agents, an increase in associated side effects has been noted. In addition to side effects one also notes the worsening or facilitation of cardiac arrhythmias. There are many case reports of quinidine causing ventricular tachycardia (VT) or fibrillation.1-4 However, this action is not unique to quinidine. There are reports implicating other available conventional agents as well as the newly developed investigational agents.5-10 However, there are few studies that have tried to look at the incidence of this problem and try to provide evidence for a causative relation between antiarrhythmic agents and their possible exacerbation of arrhythmias. Velebit et al." reported aggravation of ventricular arrhythmias in 11% of 722 drug tests. This group employs Holter monitoring techniques and bicycle exercise to evaluate the potential proarrhythmic action of antiarrhythmic drugs. Recently, Ruskin et all* reported on six survivors of out-of-hospital cardiac arrest. Using programmed electrical stimulation (PES), they showed that these patients had their life-threatening arrhythmia induced while they were receiving antiarrhythmic drugs, but the same arrhythmia was not provoked when they were not taking the drug. Poser et all3 have also used PES techniques to analyze the incidence of antiarrhythmic drug aggravation of arrhythmias. This group employs electrophysiologic studies in a minority of From the Cardi ac Arrhythmia Service, Cardiology Division,
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Pacing and Clinical Electrophysiology, 2009
Cardiac arrhythmias occur in approximately 5.3% of the population and contribute substantially to morbidity and mortality. Pharmacological therapy still remains the major approach in management of patients with nearly every form of cardiac arrhythmia. Effective and safe management of cardiac arrhythmias with antiarrhythmic drugs requires understanding of basic mechanisms for various cardiac arrhythmias, clinical diagnosis of an arrhythmia and identification of underlying cardiac diseases, pharmacokinetics, and antiarrhythmic properties of each individual antiarrhythmic drug. Most cardiac arrhythmias occur via one of the two mechanisms: abnormal impulse formation and reentry or both. Antiarrhythmic drugs primarily work via influencing cardiac automaticity or triggered activity or by their effects on effective refractoriness of cardiac cells. Proarrhythmic effects of antiarrhythmic drugs are also briefly discussed in this review article.
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Antiarrhythmic drugs play a major role in the management of the most common types of arrhythmias. The margin between the beneficial and toxic effects of these drugs is often narrow. Thus, a precise knowledge of dosages, drug-target tissue interactions, pharmacodynamics and pharmacokinetics of antiarrhythmic drugs is needed to better predict how effective a particular drug will be in the treatment of a specific arrhythmia in a given patient. Despite the large amount of information that is available on the electrophysiological and pharmacological effects of antiarrhythmic drugs, we still do not know enough about their true mechanism of action in individual patients. The results of the Cardiac Arrhythmia Suppression Trial (CAST) firmly established that the use of class I drugs is potentially dangerous in a specific subset of patients. Additionally, several meta-analyses have reported that quinidine has severe proarrhythmic effects in patients with atrial fibrillation. The management of arrhythmias in elderly patients is difficult because of age-related factors that may influence the pharmacokinetics and pharmacodynamics of antiarrhythmic drugs.
A Simple In Vivo Model to Evaluate the Effects of Antiarrhythmic Agents
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