Antiarrhythmic drugs proarrhythmic effects

Class IC antiarrhythmic drugs such as flecainide or propafenone block the Na+ channel (open state propafenone open and inactivated state) with a very long dissociation time constant so that they alter normal action potential propagation. Flecainide increased mortality of patients recovering from myocardial infarction due to its proarrhythmic effects (CAST study). Action potential is shortened in Purkinje fibres but is prolonged in the ventricles. 

Proarrhythmic effects Antiarrhythmic agents may cause new or worsened arrhythmias. It is essential that each patient be evaluated electrocardiographically and clinically prior to and during therapy to determine whether the response to the drug supports continued treatment. ... 

As with other antiarrhythmic drugs, moricizine has proarrhythmic activity, which may manifest as new ventricular ectopic beats or a worsening of preexisting ventricular arrhythmias. These effects are most common in patients with depressed left ventricular function and a history of congestive heart failure. Cardiovascular ef-... 

Proarrhythmic effects of antiarrhythmic drugs In the Cardiac Arrhythmia Suppression Trial (CAST) treatment with encainide and flecainide, two class IC antiarrhythmic agents, successfully prevented ventricular ectopic beats in patients who had myocardial infarction. However, continued therapy with either drug was associated with a two- to three-fold increase in death due to cardiac arrhythmias. Similar results were reported for moricizine. Increased death was probably due to drug-induced fatal arrhythmias triggered by recurrent myocardial ischemia. 

In contrast, amiodarone and sotalol are effective in most supraventricular and ventricular tachycardias. Amiodarone displays electrophysiologic characteristics consistent with each type of antiarrhythmic drug, ft is a sodium channel blocker with relatively fast on-off kinetics, has nonselec-tive j8-blocking actions, blocks potassium channels, and has slight calcium antagonist activity. The impressive effectiveness and low proarrhythmic potential of amiodarone have challenged the notion that selective ion channel blockade is preferable. Sotalol is a potent inhibitor of outward... 

Drug commonly induces an otherwise common illness this effect will not be discovered by informal clinical observation. If very common, it may be discovered in formal therapeutic trials and in case-control studies, but if only moderately common it may require observational cohort studies, e.g. proarrhythmic effects of antiarrhythmic drugs. 

Flecainide slows conduction in all cardiac cells including the anomalous pathways responsible for the Wolff-Parkinson-White (WPW) syndrome. Together with encainide and moricizine, it underwent clinical trials to establish if suppression of asymptomatic premature beats with antiarrhythmic drugs would reduce the risk of death from arrhythmia after myocardial infarction. The study was terminated after preliminary analysis of 1727 patients revealed that mortality in the groups treated with flecainide or encainide was 7.7% compared with 3.0% in controls. The most likely explanation for the result was the induction of lethal ventricular arrhythmias possibly due to ischaemia by flecainide and encainide, i.e. a proarrhythmic effect. In the light of these findings the indications for flecainide are restricted to patients with no evidence of structural heart disease. The most common indication, indeed where it is the drug of choice, is atrioventricular re-entrant tachycardia, such as AV nodal tachycardia or in the tachycardias associated with the WPW syndrome or similar conditions with anomalous pathways. This should be as a prelude to definitive treatment with radiofrequency ablation. Flecainide may also be useful in patients with paroxysmal atrial fibrillation. 

Hilleman DE, Larsen KE. Proarrhythmic effects of antiarrhythmic drugs. PT 1991 June 520-4. 

Morganroth J. Proarrhythmic effects of antiarrhythmic drugs evolving concepts. Am Heart J 1992 123(4 Pt 2) 1137-9. 

Fauchier JP, Babuty D, Fauchier L, Rouesnel P, Cosnay P. Les effets proarythmiques des antiarythmiques. [Proarrhythmic effects of antiarrhythmic drugs.] Arch Mai Coeur Vaiss 1992 85(6) 891-7. 

Amiodarone is a Type III antiarrhythmic agent. It has been shown in several clinical trials to be safe and effective in the treatment of supraventricular and ventricular arrhythmias in patients with cardiovascular disease. Amiodarone is also associated with fewer proarrhythmic effects compared with other antiarrhythmic drugs. Amiodarone is empirically dosed and adjusted based on efficacy and toxicity. 

In approximately 50% of cases, antiarrhythmic drugs are required in patients with ICDs to reduce the frequency of recurrent ventricular arrhythmias (199). Antiarrhythmic drugs may also be necessary to suppress atrial arrhythmias, which may interfere with proper detection and lead to inappropriate shocks (200,201). In both situations, drugs must be used judiciously because of potential drug-device interactions. Drugs can (a) slow ventricular tachycardia below the programmed rate cutoff, (b) increase energy threshold to defibril-late, (c) have an effect on pace termination of ventricular tachycardia, (d) be proarrhythmic, and (e) cause bradycardia and AV block. The process of... 

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