Sotalol antiarrhythmic effects

Sotalol possesses a broad spectrum of antiarrhythmic effects in ventricular and supraventricular arrhythmias. It has value in the management of patients with paroxys-... 

Local anesthetic action, also known as "membrane-stabilizing" action, is a prominent effect of several 3 blockers (Table 10-2). This action is the result of typical local anesthetic blockade of sodium channels (see Chapter 26) and can be demonstrated experimentally in isolated neurons, heart muscle, and skeletal muscle membrane. However, it is unlikely that this effect is important after systemic administration of these drugs, since the concentration in plasma usually achieved by these routes is too low for the anesthetic effects to be evident. These membrane-stabilizing 3 blockers are not used topically on the eye, where local anesthesia of the cornea would be highly undesirable. Sotalol is a nonselective 3-receptor antagonist that lacks local anesthetic action but has marked class III antiarrhythmic effects, reflecting potassium channel blockade (see Chapter 14). 

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... 

Sotalol is a beta-blocker that also has class III antiarrhythmic effects, It causes prolongation of the Q-T interval and is recommended solely as an antiarrhythmic. It is included in this section because it is subject to interactions from its betablocking properties as well as its Q-T prolongation... 

In an analysis of cases of torsade de pointes associated with fluoroquinolones on the FDA Adverse Events Reporting System database, two cases of torsade de pointes were noted in patients taking a fluoroquinolone with sotalol (there were 37 cases identified, and 19 occurred in patients also taking other drugs known to prolong the QT interval). Sotalol has class III antiarrhythmic effects and prolongs the QT interval, and this could be additive with the effects of quinolones that prolong the QT interval (e.g. gat-ifloxacin, moxifloxacin, sparfloxacin, see Table 9.2 , (p.257)). The... 

The Vaughan-Williams classification of antiarrhythmic drugs has been criticized for a number of reasons. The classification is based on the effects of drugs on normal, rather than diseased, myocardium. In addition, many of the drugs may be placed into more than one class. For example, the class IA drugs prolong repolarization/refractoriness, either via the parent drug8,9 or an active metabolite,10 and therefore also maybe placed in class III. Sotalol is also a 3-blocker, and therefore fits into class II. Amiodarone inhibits sodium and potassium channels, is a non-competitive inhibitor of 3-receptors, and inhibits calcium... 

ICDs have been found to be significantly more effective than antiarrhythmic agents such as amiodarone or sotalol for reducing the risk of sudden cardiac death 45,46 therefore, ICDs are preferred therapy.44 However, many patients with ICDs receive concurrent antiarrhythmic drug therapy to reduce the frequency with which patients experience the discomfort of shocks and to prolong battery life of the devices. Combined pharmacotherapy with amiodarone and a 3-blocker is more effective than monotherapy with sotalol or (i-blockers for reduction in the frequency of ICD shocks.47... 

Singh, B.N. (1990) in A Symposium ControlUng Cardiac Arrhythmias with Sotalol, a Broad-Spectrum Antiarrhythmic with Beta-Blocking Effects and Class III Activity (Singh, B.N., ed.). Am. J. Cardiol. 65 No. 2 pp. 3A-11 A. 

Transfer to sotalol from other antiarrhythmic therapy- Before starting sotalol, generally withdraw previous antiarrhythmic therapy under careful monitoring for a minimum of 2 to 3 plasma half-lives if the patient s clinical condition permits. Treatment has been initiated in some patients receiving IV lidocaine without ill effect. After discontinuation of amiodarone, do not initiate sotalol until the QT interval is normalized. 

Proarrhythmia Like other antiarrhythmic agents, sotalol can provoke new or worsened ventricular arrhythmias in some patients, including sustained ventricular tachycardia or ventricular fibrillation, with potentially fatal consequences. Because of its effect on cardiac repolarization, is the most common form of proarrhythmia associated with sotalol, occurring in approximately 4% of high-risk patients. 

Uses Rapid conversion of AF/artmal fluto Action Class III antiarrhythmic Dose Adults >60 kg. 0.01 mg/kg (max 1 mg) IV inf over 10 min may repeat x 1 <60 kg Use 0.01 mg/kg (ECC 2005 D/C cardioversion preferred) Caution [C, -] Contra w/ class I/III antiarrhythmics (Table VI-7) QTc >440 ms Disp Inj SE Arrhythmias, HA Interactions t Refractory effects W7 amiodarone, disopyra-mide, procainamide, quinidine, sotalol t QT int val W7 antihistamines, antidepressants, erythromycin, phenothiazines, TCAs EMS Use antihistamines w/ caution, may T QT interval OD May cause increased repolarization leading to arrhythmias, bradycardia, hypotension leading to cardiac arrest symptomatic and supportive... 

Blockers are antiarrhythmics of class II according to the Vaughan-Williams classification, effective in the treatment of both supraventricular and ventricular tachyarrhythmias. These drugs can also reduce ectopic beats, especially if they are a result of sympathetic activity. Sotalol is a racemic mixture of the -blocking L-isomer and the class III antiarrhythmic D-isomer. This racemic mixture as well as D-sotalol are used as class Ill-antiarrhythmic. 

Sotalol, as the racemate (a 1 1 mixture of the d- and 1-enantiomers), has a well-documented class Ill-antiarrhythmic activity, without showing the various side-effects of amiodarone. The -adrenoceptor blockade by this agent, however, limits its use in patients with heart failure. Dofetilide is an example of a newer, rather pure class in-antiarrhythmic, virtually devoid of other pharmacological properties. 

Ibutilide (Corvert) is a structural analog of sotalol and produces cardiac electrophysiological effects similar to those of the antiarrhythmic agents in class III. 

A systematic review of randomized controlled trials in patients with newly detected AF identified a number of antiarrhythmic drugs for which there was statistically significant evidence of benefit (I). In a limited number of comparative studies, flecainide was more effective than propafenone and procainamide, propafenone was superior to amiodarone, amiodarone was superior to quinidine, and quinidine was superior to sotalol. 

PROPAFENONE I. ANTIARRHYTHMICS - disopyra-mide, procainamide 2. ANTIBIOTICS - macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafaxine 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine 8. ANTI-M ALARIALS - artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS - pentamidine isetionate 10. ANTIPSYCHOTICS-atypicals, phenothiazines, pimozide II. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS -parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs prolong the Q-T interval. Also, amitriptyline, clomipramine and desipramine levels may be t by propafenone. Amitriptyline and clomipramine may t propafenone levels. Propafenone and these TCAs inhibit CYP2D6-mediated metabolism of each other Avoid co-administration... 

Although the antiarrhythmics have been entered into this classification according to a characteristic major action, most have other effects as well. For example, quinidine (class I) has major class III effects propranolol (class II) has minor class I effects, and sotalol (class II) has major class III effects. Amiodarone has class I, II, III and IV effects but is usually classed under III. 

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