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New Antiarrhythmic Drugs: Their Place in Therapy

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Summary

Cardiac arrhythmias remain the leading cause of cardiac deaths and disability in patients with heart disease. Therapy is often a challenge for the physician since currently available drugs may be ineffective or cause unpleasant or life-threatening adverse effects, and require frequent administration. Recent advances in monitoring and invasive electrophysiological procedures allow diagnoses to be made more accurately and specific antiarrhythmic drug therapy to be evaluated more closely. Antiarrhythmic agents are classified most frequently according to their effects on the cardiac action potential (Vaughan Williams classification). Class I agents have membrane or quinidine-like effects and decrease the rate of rise of phase 0 of the action potential. They may lengthen or shorten the duration of the action potential. Class II agents are competitive β-blockers, and class III agents increase the action potential duration and may have a non-competitive β-blocking effect. Class IV agents are those that have an antiarrhythmic effect due to their actions as calcium antagonists.

This review presents several new drugs in classes I, III and IV with brief descriptions of their haemodynamics, electrophysiology and pharmacokinetics, where these have been studied, and discusses clinical use, dosage and administration, and adverse effects of these new agents. Several of the drugs discussed have been used for years in some areas of the world, while others are relatively new everywhere. Data on a number of these new agents are incomplete and little is known about their long term use. However, in each case, their use is becoming more widespread.

Salient features of each drug follow. Ajmaline is a class I agent, used to detect patients with atrioventricular conduction system disease or accessory pathways with very short refractory periods in Wolff-Parkinson-White syndrome. Amiodarone is a class III agent with a very long half-life, effective in many atrial and ventricular arrhythmias but with several long term side effects. Aprindine is a class I agent, effective in many arrhythmias, but it may cause leucopenia and, rarely, agranulocytosis. Bretylium is a class III agent, useful in the short term therapy of refractory haemodynamically unstable ventricular tachycardia or ventricular fibrillation. Disopyramide is a class I agent, with characteristics similar to quinidine. Unfortunately, it produces heart failure when depressed ventricular function exists. Encainide is also a class I agent, which has been shown to be very effective in ventricular tachycardia and premature ventricular complexes in initial reports. Ethmozin is a phenothiazine derivative developed in the USSR and used in both atrial and ventricular arrhythmias. Flecainide, a very new class I agent with a long half-life, is reported to be effective in both atrial and ventricular arrhythmias, although studies to date have been few. Lorcainide, a class I agent, suppresses PVCs, but may cause sleep disturbances in many patients. Mexilitine, another class I agent, is effective in ventricular arrhythmias, but has dose-related neurological adverse effects and a narrow toxic-therapeutic ratio. N-Acetylprocainamide, the major metabolite of procainamide, does not cause the lupus-like syndrome the parent compound does. However, it is less active as an antiarrhythmic agent. Tocainide, an analogue of lignocaine (lidocaine) with a long half-life, can be administered orally, and is effective in ventricular arrhythmias. Verapamil has class IV action and is primarily effective in treating and preventing supraventricular arrhythmias.

These new agents provide two approaches for improving antiarrhythmic drug effects. Firstly, some offer better pharmacokinetic characteristics for improved dosing or routes of administration; for example, tocainide. Secondly, different electrophysiological actions are noted in several; for example, encainide and amiodarone. These agents promise to broaden the clinical approach for treating and preventing arrhythmias in cardiac patients.

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Keefe, D.L.D., Kates, R.E. & Harrison, D.C. New Antiarrhythmic Drugs: Their Place in Therapy. Drugs 22, 363–400 (1981). https://doi.org/10.2165/00003495-198122050-00002

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