Gene/Protein Disease Symptom Drug Enzyme Compound
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 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sotalol is a unique beta-adrenergic blocking agent with additional actions characteristic of Vaughn-Williams class III antiarrhythmic agents in experimental models. To test the efficacy of sotalol to suppress ventricular arrhythmias, a 6 week parallel, placebo-controlled out-patient study of two doses (320 and 640 mg/day, in two divided doses) was performed in four hospitals in 56 patients with chronic premature ventricular complexes at a frequency of 30/h or more (mean +/- SE, 528 +/- 60/h) on 48 hour ambulatory electrocardiographic recording. During a placebo week, no change occurred in arrhythmia frequency (532 +/- 76/h). Subsequent sotalol therapy significantly reduced median arrhythmia frequency in patients receiving both low (n = 19) and high (n = 18) doses compared with that in patients receiving placebo (by 77 and 83%, respectively, versus 6%; p less than 0.001). Twenty-two (59%) of 37 sotalol-treated patients, 11 in each group, reached the prospectively defined criterion of efficacy (greater than or equal to 75% arrhythmia reduction) versus 2 (11%) of 19 placebo control patients (p less than 0.001). Sotalol reduced the median frequency of couplets by 94% (p less than 0.0001) and that of runs by 89% (p less than 0.0007). The electrocardiographic effects of sotalol included reductions in heart rate (by 17 to 27%) and increases in the QTc (by 6 to 9%) and PR (by 6%) intervals. Ejection fraction was unchanged. The most common adverse side effect was fatigue, but drug discontinuation was required in only three patients taking 640 mg/day. No proarrhythmic events or biochemical abnormalities were observed. In summary, sotalol displays significant antiarrhythmic activity of moderately high degree with good tolerance in doses of both 320 and 640 mg/day. Its antiarrhythmic actions are distinguished from those reported for other beta-blockers by its effects on the QTc interval and its moderately high degree of antiarrhythmic activity.
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PMID:Multicenter trial of sotalol for suppression of frequent, complex ventricular arrhythmias: a double-blind, randomized, placebo-controlled evaluation of two doses. 242 52

Sotalol was given for extended therapy to 22 of 29 patients with frequent (greater than or equal to 30/hour) complex premature ventricular complexes (PVCs) who had participated in a short-term study of sotalol vs placebo. Open-label sotalol was given in individually titrated divided doses of 160 to 800 mg/day (median 323, mean 386 mg/day). Response was assessed at approximately 1, 6, and 12 months or until patient discontinuation. The period of sotalol therapy averaged 9 months (range, 0.2 to 22.7). At about 1 month, 13 (59%) of 22 patients showed effective control of arrhythmia. The median percentage change in total PVCs for individual patients at 1 month was -70% and for repetitive PVCs it was -95%. At about 6 months, 10 (45%) of the 22 patients continued to be successfully treated; at about 12 months, seven patients continued on sotalol, six (27%) successfully treated according to Holter criteria. Reasons for discontinuation included lack of efficacy in nine, adverse effects in four (fatigue in three, bradycardia with sinus pauses in one), and miscellaneous reasons in two. ECG PR and especially QTc intervals increased significantly during therapy (p less than 0.02, p less than 0.01, respectively). In summary, sotalol is a moderately effective antiarrhythmic agent in patients with complex PVCs, but during long-term therapy a rather high dropout rate was observed because of arrhythmia recurrence or adverse effects.
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PMID:Long-term experience with sotalol in the treatment of complex ventricular arrhythmias. 360 85

Sotalol is a beta-blocking drug devoid of membrane stabilizing properties, as well as intrinsic sympathomimetic actions, or cardioselectivity. In addition, sotalol prolongs atrial and ventricular repolarization (Class III antiarrhythmic activity). It appears to have less myocardial depressant effect than other beta-blocking agents. Given orally, bioavailability of the drug reaches 100%. Sotalol's plasma half-life is 15 hours (range 7-18) and is dependent only on renal function. In clinical practice, it has been found effective in the suppression of nearly all supraventricular and ventricular dysrhythmias except those related to prolonged ventricular repolarization. Most common adverse effects are dyspnea, bradycardia, and fatigue, which results in drug termination in 16% of the cases. Torsades de pointes usually associated with bradycardia and drug induced QTc prolongation has been reported in 1.9%-3.5% of the patients receiving sotalol. This complication may be reduced by limiting the dose (< 640 mg/day) especially in patients with impaired renal function. In addition hypokalemia must be avoided. To sum up, the combination of Class II and Class III effects may carry additional benefits. However, further studies are required to test such hypotheses.
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PMID:Sotalol: from "just another beta blocker" to "the prototype of class III antidysrhythmic compound". 777 Mar 66

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of sotalol hydrochloride are reviewed. The chemical name of sotalol hydrochloride is 4'-[1-hydroxy-2-(isopropylamino)ethyl]methanesulfonanilide monohydrochloride. Sotalol is a class III antiarrhythmic that prolongs the action potential and refractoriness of cardiac tissue and has potent nonselective beta-blocking activity. Sotalol is well absorbed after oral administration. The pharmacokinetics of sotalol can be described by an open, linear, two-compartment model. The drug is eliminated primarily by the kidneys; mean elimination half-life is 12 hours. Sotalol has been found to be effective in controlling life-threatening ventricular arrhythmias, including sustained ventricular tachycardia, ventricular fibrillation, and premature ventricular complexes. Although sotalol has FDA-approved labeling for use in the treatment of ventricular arrhythmias only, it is also effective against a variety of supraventricular arrhythmias. Noncardiac adverse effects include fatigue, impotence, depression, headache, nausea, diarrhea, and increased triglyceride levels. Cardiovascular adverse effects include atrioventricular block, bradycardia, hypotension, exacerbation of heart failure, and polymorphic ventricular tachycardia. Overall, 11-21% of patients experience adverse effects; 6-18% of these patients have reactions serious enough to warrant the discontinuation of sotalol therapy. The initial dosage of oral sotalol hydrochloride in adults is 80 mg twice daily or 160 mg once daily; the dosage can be increased every three to four days in increments of 40-160 mg/day to a maximum of 480 mg/day. Sotalol is useful in the control of intractable, life-threatening ventricular arrhythmias, as well as a variety of supraventricular arrhythmias, in patients who do not respond to or are intolerant of more conventional antiarrhythmics.
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PMID:Sotalol: a new class III antiarrhythmic agent. 813 5

Two trial designs have been used in evaluating sotalol in patients with sustained tachyarrhythmias: open-label dose escalation and randomized comparison with reference agents. At least 7 open-label studies (n = 16-65) have been reported from single centers in patients in whom trials of numerous other antiarrhythmic agents were unsuccessful. At the doses used, usually 320-640 mg/day, plasma concentrations were in the range associated with both beta blockade and class III antiarrhythmic activity (2-3 micrograms/mL). These concentrations produced electrophysiologic changes that were consistent across studies: 10-16% increase in right ventricular effective refractory period (ERP), 4-8% increase in corrected QT interval (QTc), and 17-30% increase in sinus cycle length (corresponding to a 15-23% decrease in heart rate). In these open-label trials, sotalol suppressed inducible ventricular tachyarrhythmias in 20-72% of patients; the higher degrees of efficacy were reported when induction protocols were confined to double extrastimuli. Side effects leading to discontinuation of sotalol in patients with sustained ventricular tachycardia or fibrillation include fatigue (4.0%), marked bradycardia (3.0%), torsades de pointes (3.0%), and heart failure or pulmonary edema (1.0%). A multicenter randomized trial compared intravenous sotalol with intravenous procainamide in a double-blind prospective fashion. Sotalol suppressed ventricular tachyarrhythmias inducible with triple extrastimuli in 15 (30%) of 50 patients, whereas procainamide was effective in 10 (20%) of 50. In this and other series, responsiveness to sotalol was prospectively identified by a particularly fast tachycardia at baseline (e.g., cycle length of < 270 msec), but not by the extent of changes in global indices of repolarization (QTc, ERP).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Usefulness of sotalol for life-threatening ventricular arrhythmias. 834 27

Atrial tachycardias, in particular atrial flutter after surgery for congenital heart disease, is associated with a high mortality. Treatment with various antiarrhythmic drugs and/or antitachycardia pacemakers is not very successful. Sotalol, a Class III drug, has shown to be a promising drug in adults with atrial tachycardias. However, the experience with sotalol in children after surgery for congenital heart disease is limited. Therefore, we describe our results here. Between December 1990 and February 1997, 26 children with atrial tachycardias, most of them with atrial flutter or fibrillation (n = 20), after surgery for congenital heart disease were treated with sotalol orally. The age of the children at the start of treatment was 7.5 +/- 5.8 years (mean +/- SD). The time interval between surgery and the start of atrial tachycardia ranged from 1 day to 14.3 years (3.8 +/- 3.8 years). Conversion to sinus rhythm was achieved in 16 out of 22 hemodynamically stable children with a dosage of 4.0 +/- 1.6 mg/kg per day. The six children without sinus rhythm on sotalol and four hemodynamically unstable patients were treated prophylactically with sotalol after DC cardioversion for their tachycardias. Two children complained of mild transient fatigue. Heart rate decreased during therapy (95 +/- 33 vs 81 +/- 21 beats/min; P = 0.01). QTc-intervals did not change. Proarrhythmias such as torsades de pointes were not encountered. Two children with a preexistent sick sinus syndrome showed aggravation of bradycardia and needed pacemaker implantation. The percentage of children with a recurrence-free interval of 1 and 2 years was 96% and 81%, respectively, for all atrial tachycardias, and 92% and 66% for atrial flutter. The recurrences of atrial tachycardias during the follow-up period, which ranged from 0.1-6.1 years (2.5 +/- 1.8 years) could be treated with only an increase of the dosage of sotalol in all but one patient. We conclude that sotalol is an effective drug for the treatment and prevention of atrial tachycardia in children after surgery for congenital heart disease.
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PMID:Sotalol for atrial tachycardias after surgery for congenital heart disease. 927 23