Disease relevance of sotalol

• The risk of a recurrence of arrhythmia was significantly lower in patients who received sotalol than in those who received other antiarrhythmic drugs, and the risk was lower in those who had not previously failed to respond to antiarrhythmic drugs than in those who had [1].
• METHODS: We undertook a prospective, multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone [2].
• In patients similar to those in this study, if antiarrhythmic-drug therapy is to be used to prevent recurrences of ventricular tachyarrhythmias, treatment with sotalol and assessment of its potential efficacy by Holter monitoring are a reasonable initial strategy [3].
• As compared with other antiarrhythmic agents, sotalol prevents recurrences of arrhythmia in a higher proportion of patients, particularly among those presenting with ventricular tachycardia and aborted sudden cardiac death [4].
• Controlled trial of sotalol for one year after myocardial infarction [5].

Psychiatry related information on sotalol

• In an alternate therapy group (n = 41) of similar patients previously refractory to or intolerant of procainamide, intravenous sotalol prevented inducibility in 32% [6].
• The effects of sotalol on EEG, sleep, and performance in psychological tests were equivocal and do not yield evidence for CNS activity of sotalol [7].
• The effects of sotalol on heart rate, blood pressure, EEG, subjective quality of sleep, polygraphically determined sleep pattern, and psychophysiological parameters such as psychomotor performance, memory, perception, vigilance, and general condition were studied and were related to dosage and plasma levels [7].
• The beta-adrenergic antagonists sotalol, nadolol and timolol (which act at both beta 1- and beta 2-receptors) induce amnesia in the domestic chick when given systemically after a one trial passive avoidance task [8].

High impact information on sotalol

• METHODS: In a multicenter trial, patients were stratified according to left ventricular ejection fraction (< or =0.30 or >0.30), randomly assigned to double-blind treatment with 160 to 320 mg of sotalol per day (151 patients) or matching placebo (151 patients), and followed for 12 months [9].
• CONCLUSIONS: Oral sotalol was safe and efficacious in reducing the risk of death or the delivery of a first defibrillator shock whether or not ventricular function was depressed [9].
• Although initially marketed in the United States for treatment of life-threatening ventricular arrhythmias, sotalol also has demonstrated efficacy in many patients with supraventricular arrhythmias [4].
• Tachycardia persisted in 14 patients in the lignocaine group and 4 in the sotalol group after 15 min [10].
• The addition of a low dose of aspirin to sotalol treatment showed significant benefit in terms of cardiovascular events, including a significant reduction in the incidence of first myocardial infarction in patients with symptoms of stable angina pectoris [11].

Chemical compound and disease context of sotalol

• CONCLUSIONS: Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation [2].
• Double-blind trial of lignocaine versus sotalol for acute termination of spontaneous sustained ventricular tachycardia [10].
• Furthermore, 34% of the patients treated with sotalol and 22% of the patients treated with quinidine relapsed into atrial fibrillation (NS) [12].
• Clinically used doses of procainamide and propafenone terminated atrial fibrillation in 13 of 13 (100%) and 7 of 10 (70%) dogs, respectively, but a dose of sotalol (2 mg/kg IV) in the clinical range terminated atrial fibrillation in only 2 of 8 (25%) dogs (P = .0005 vs procainamide, P = .08 vs propafenone) [13].
• CONCLUSIONS: In this case-control study, ICD therapy was more effective tha electrophysiologically guided antiar-rhythmic treatment with d,l-sotalol in prevention of sudden death and reduction of total morality in patients with coronary artery disease [14].

Biological context of sotalol

• Effect of sotalol on normal intraocular pressure [15].
• Sotalol is a beta-adrenergic blocker that also prolongs action potential duration and myocardial refractoriness over the short term (class III effect) [16].
• Sotalol reduced peak exercise heart rate by 13.8 +/- 7% at the dosage of 320 mg/24 hr and by 25.4 +/- 8% at the dosage of 640 mg/24 hr (both p less than 0.01) [17].
• Sex difference in risk of torsade de pointes with d,l-sotalol [18].
• Treatment of fetal tachycardia with sotalol: transplacental pharmacokinetics and pharmacodynamics [19].

Anatomical context of sotalol

• The purpose of this study was to compare the long-term efficacy of d,l-sotalol and ICDs in patients with coronary artery disease [14].
• Sotalol differentially increases refractoriness in potential reentry circuits in ischemic myocardium [16].
• Severe adverse effects, including congestive heart failure and sinus node dysfunction, were noted early during sotalol therapy in three patients [20].
• Intravenous sotalol lengthened the ERP in the atrium (+24.6%, p less than .01), atrioventricular node (+24.9%, p less than .01), and ventricle (+14.9%, p less than .01) [21].
• [3H]Dofetilide is displaced from guinea pig myocytes by dofetilide, clofilium, quinidine, sotalol, and sematilide with a rank order of potency that correlates with functional blockade of the rapidly activating delayed rectifier K+ current (correlation coefficient, 0.951; slope, 0.99 +/- 0.19; p = 0.014) [22].

Associations of sotalol with other chemical compounds

• Quinidine also increased mean left ventricular ejection fraction, but less so than did sotalol (p less than .05) [23].
• In contrast, the beta antagonist, sotalol, and the alpha 1 antagonist, prazosin, were found ineffective when similarly applied [24].
• Kaplan-Meyer analysis identified New York Heart Association class II or III (p = 0.021), ejection fraction < 0.40 (p = 0.027), spontaneous (p<0.001) or inducible (p<0.001) monomorphic VTs and the use of class III antiarrhythmic drugs (amiodarone, p<0.001; sotalol, p = 0.004) as risk predictors of VTs above the TDI [25].
• Following baseline measurements, all patients were randomized either to double-blind intravenous infusion of sotalol (1.0 mg/kg) or metoprolol (0.1 mg/kg) [26].
• After cardioversion, sinus rhythm can be maintained with class I and III drugs, such as flecainide and propafenone or amiodarone and sotalol [27].

Gene context of sotalol

• Class III agents like dofetilide, clofilium, and sotalol, which can all cause a drug-induced form of LQT2, significantly lengthen action potential duration at 50% and 90% repolarization in isolated rabbit Purkinje fibers, and can initiate the formation of early afterdepolarizations, and extra beats [28].
• The efficacy of d/l sotalol was investigated in 50 patients (43 men, seven women; 33 with coronary artery disease, 15 with dilated cardiomyopathy; ejection fraction 33 +/- 10%) with inducible sustained ventricular tachycardia [29].
• Log dose-response curves for increases in both heart rate (mostly beta 1), and amplitude of physiologic tremor (beta 2) were constructed for each subject in the control state and 2 hr after 10 or 40 mg propranolol, 200 mg sotalol, or placebo [30].
• The effect of isoproterenol on glutamine synthetase was inhibited by the beta-adrenergic blocking agent sotalol [31].
• Stress-induced iliac dilation was eliminated by the nonselective beta-adrenoceptor antagonist sotalol [32].

Analytical, diagnostic and therapeutic context of sotalol

• Prevention of implantable-defibrillator shocks by treatment with sotalol. d,l-Sotalol Implantable Cardioverter-Defibrillator Study Group [9].
• In a randomized, crossover study, three dosages of sotalol (160 mg/24 hr, 320 mg/24 hr, and 640 mg/24 hr) were administered during 4 days to each subject [17].
• Programmed electrical stimulation predicted clinical outcome in 63% after intravenous and in 86% after oral sotalol [33].
• METHODS AND RESULTS: In a database derived from 22 clinical trials involving 3135 adult patients who received oral d,l-sotalol (median follow-up, 164 days), TdP developed in 44 (1.9%) of 2336 men and in 33 (4.1%) of 799 women (P < .001) [18].
• We studied the physiological rate dependence of sotalol effects on ventricular repolarization, measured as QT interval duration on the surface electrocardiogram at rest and during a maximal exercise test, in 10 normal volunteers [17].

References