Sotalol

Abstract

Sotalol¹ is a β- adrenoceptor blocking agent devoid of intrinsic sympathomimetic activity, membrane stabilising actions and cardioselectivity. It lengthens repolarisation and the effective refractory period in all cardiac tissues independently of its antiadrenergic properties. Combining Class II and Class III antiarrhythmic properties, sotalol can be given either intravenously or orally and its pharmacokinetic properties permit long dosing (once or twice daily) intervals. Controlled and uncontrolled studies have established the efficacy of sotalol in mild- to- moderate essential hypertension and in angina of effort. Sotalol reduces anginal frequency and glyceryl trinitrate (nitroglycerin) consumption and increases exercise capacity during treadmill stress tests. In addition, although there is evidence that the drug reduces reinfarction rate in survivors of acute infarction, the data for reduction in sudden death rates in these patients are not as compelling as for other β- blockers. However, comparative and additional long term studies are required before an accurate assessment of the use of sotalol in these disorders can be made. When used in the treatment of mild- to- moderate hypertension sotalol is more effective than placebo and comparable to other β- blockers in reducing elevated blood pressures. In addition, a synergistic antihypertensive response is achieved when sotalol is combined with hydrochlorothiazide. Still, additional well- controlled comparative studies are required before the value of sotalol relative to other drug treatment regimens in the management of hypertension can be made. In preliminary studies sotalol appeared effective in most forms of supraventricular tachyarrhythmias with its effects being similar to those of other β- blockers. However, preliminary data indicate that sotalol is likely to be more effective than conventional β- blockers in converting atrial flutter and fibrillation to sinus rhythm and maintaining stability post- conversion. Sotalol also appears to be a promising agent in the control of ventricular arrhythmias. In suppressing premature ventricular contractions it is at least as effective as procainamide. In ventricular tachycardia and fibrillation, intravenous sotalol (1.5 mg/ kg), prevents reinduction by programmed electrical stimulation in 40 to 50% of cases if double stimuli are used. Both prevention of reinducible arrhythmia and the suppression of spontaneous arrhythmias on Holter recordings are predictive of a long term favourable clinical outcome. In patients with reduced ejection fractions, sotalol depresses ventricular function less than conventional β- blockers. The side effects of sotalol are related to its β- blocking activity and to its property of prolonging the QTc interval. The overall proarrhythmic effect is low but torsade de pointes may develop in conjunction with excessive lengthening of the QTc interval, bradycardia, hypokalaemia, and high plasma concentrations of the drug. In summary, sotalol is a promising antiarrhythmic agent with a favourable pharmacokinetic and haemodynamic profile and a low incidence of proarrhythmic effects. Its future role in the treatment of angina pectoris and hypertension remains to be seen, and its role as an antiarrhythmic agent with a broad spectrum of activity in supraventricular and ventricular tachyarrhythmias merits further critical evaluation. In both animals and man, the pharmacodynamic properties of sotalol are dominated by a composite effect of β-blockade and the propensity to prolong the cardiac action potential duration. Sotalol has one-third the β-blocking potency of propranolol; it is devoid of intrinsic sympathomimetic actions and is not cardioselective. The drug prolongs the action potential duration in atria, ventricle, and the His-Purkinje fibres in a dose-dependent fashion at ‘lower’ concentrations, but shortens the action potential duration at very high concentrations by reducing the upstroke velocity of the action potential. In man, intravenous sotalol slows the heart rate, lengthens the PR and AH intervals (mean 18%), and prolongs the effective refractory period in the atria (25%), AV node (25%), ventricle (15%) and the bypass tracts (retrograde and anterograde) of the heart. It has little effect on the His-Purkinje conduction. Sotalol also acutely prolongs the action potential duration in contrast to propranolol. Following sotalol administration the QTc interval lengthens variably, and to a greater extent after long term administration than following acute intravenous injections. Sinus node recovery time is prolonged by the drug. Recording of the monophasic action potentials in man has confirmed the in vitro data of the effect of sotalol on transmembrane action potentials. The effects of sotalol on cardiac repolarisation occur independently of its β-blocking actions since its dextro isomer (having one-fiftieth the β-blocking actions of the levo compound) is equipotent with the racemate or the levo isomer in prolonging the cardiac action potential. Haemodynamic studies following intravenous injections of sotalol have reported that the drug reduces heart rate, cardiac index and stroke work index without changing stroke volume index or increasing left ventricular end-diastolic pressure. This differs from other β-blockers, which invariably increase the filling pressure of the left ventricle. In doses of 0.2 to 0.6 mg/kg intravenously, sotalol affects only the rate-dependent functions in patients with heart failure without aggravating the heart failure. In patients with markedly reduced left ventricular ejection fraction and life-threatening ventricular arrhythmias, sotalol induces a modest increase in the ejection fraction, with rare cases of heart failure being exacerbated by the orally administered drug during long term therapy. It appears...