Sotalol Amiodarone

AF often recurs after initial cardioversion because most patients have irreversible underlying heart or lung disease. A metaanalysis confirmed that quinidine maintained sinus rhythm better than placebo however, 50% of patients had recurrent AF within 1 year, and more importantly, quinidine increased mortality, presumably due in part to proarrhythmia. Type Ic (e.g., flecainide, propafenone) and type III (e.g., amiodarone, sotalol, dofetilide) antiarrhythmic agents may be alternatives to quinidine however, these agents are also associated with proarrhythmia. Consequently, chronic antiarrhythmic drugs should be reserved for patients with recurrent paroxysmal AF associated with intolerable symptoms during episodes of AF. 

Congenital or acquired QTprolongation Patients with congenital QT prolongation and those taking Class lA (eg, quinidine, procainamide) or Class III (eg, amiodarone, sotalol) antiarrhythmic medications should avoid using vardenafil. 

Amiodarone, sotalol, quinidine, disopyramide Terfenadine, astemizole... 

Ketanserin should not be combined with drugs that prolong the QT interval, e.g. class la anti-arrhythmics, amiodarone, sotalol, erythromycin. The risk of torsade de pointes secondary to hypokalaemia is increased when ketanserin is combined with thiazides or loop diuretics without concomitant use of a potassium-sparing diuretic or an angiotensin-converting enzyme (ACE) inhibitor, a 1 Antagonists... 

As with some other quinolones, moxifloxadn also prolongs the QTC interval [265], although the prolongation time of 4—6 ms (i.e., 1.4—1.6% of the starting interval) is relatively minimal. For safety reasons, the treatment of patients with QT interval prolongation and certain cardiac diseases is therefore contraindicated. Other medicaments with a potential for prolonging the QT interval may not be administered simultaneously with moxifloxacin. These indude anti-arrhythmic drugs of class IA (e.g., quinidine, hydroquinidine, disopyramide) and III (e.g., amiodarone, sotalol, dofetilide, ibutilide), intravenous erythromydn, tricyclic anti-depressives, and cisapride etc. 

The safety of antidysrhythmic drugs in children has not been thoroughly studied. However, the risk of prolongation of the QT interval seems to be considerably less than that in adults (226), although it has been reported with quinidine, disopyramide, amiodarone, sotalol, and diphemanil. 

Kochiadakis GE, Marketou ME, Igoumenidis NE, Chrysostomakis SI, Mavrakis HE, Kaleboubas MD, Vardas PE. Amiodarone, sotalol, or propafenone in atrial fibrillation which is preferred to maintain normal sinus rhythm Pacing CUn Electrophysiol 200023(11 Pt 2) 1883-7. 

Type III antiarrhythmics include agents that specifically prolong refractoriness in atrial and ventricular tissue. This class includes very different drugs bretylium, amiodarone, sotalol, ibutilide, and recently, dofetilide they share the common effect of delaying repolarization by blocking potassium channels. The electrophysiologic actions of bretylium are related to its multifaceted pharmacology. 

III amiodarone, sotalol ACEIs captopril, etc., and ARBs losartan, etc. ... 

III Block of repolarizing potassium channels, prolongation of action potential Amiodarone, Dronedarone, Sotalol, Dofetilide, Ibutilide... 

Ventricular extrasystoles are treated only if they may degenerate into life-threatening arrhythmia. In milder forms the proarrhythmic risk of the diugs overshadows their benefits. In such cases (3-adrenoceptor antagonists may be attempted. For the treatment of ventricular extrasystoles, such as series or runs of extrasystoles, amiodarone or sotalol are used. In the absence of structural heart disease, class I anti-arrhythmic diugs can be considered an alternative. However, they may not be administered during the post-infarction period. 

Ventricular fibrillation should be terminated by electrical defibrillation. Alternatively, lidocaine can be injected intravenously. In cases with lower frequency, ventricular tachyarrhythmia class I diugs such as aj marine, flecainide or propafenone are more effective as a result of the use-dependence of lidocaine. For prophylaxis treatment, amiodarone or sotalol may be helpful or the implantation of a cardioverter-defibrillator system. Acute amiodarone (i.v. in higher doses) can also terminate ventricular tachyarrhythmias. This action, however, seems to be mediated by its INa-blocking side effects and not (or less) by its class III like effects. 

Concurrent use of the fluoroquinolones with theophylline causes an increase in serum theophylline levels. When used concurrently with cimetidine, the cimetidine may interfere with the elimination of the fluoroquinolones. Use of the fluoroquinolones with an oral anticoagulant may cause an increase in the effects of the oral coagulant. Administration of the fluoroquinolones with antacids, iron salts, or zinc will decrease absorption of the fluoroquinolones. There is a risk of seizures if fluoroquinolones are given with the NSAIDs. There is a risk of severe cardiac arrhythmias when the fluoroquinolones gatifloxacin and moxifloxacin are administered with drains that increase the QT interval (eg, quini-dine, procainamide, amiodarone, and sotalol). 

Singh S, Singh B, Reda D, et al. [Abdellatif M]. Comparison of sotalol vs. amio-darone in maintaining stability of sinus rhythm in subjects with atrial Fibrillation (Sotalol-Amiodarone Atrial Fibrillation Effectiveness Trial [SAFE-T]). Am J Cardiol 2003 92 468-72. 

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... 

As stated above, amiodarone (11), bretylium (12), sotalol (13) and clofilium (14) are prototype Class III electrophysiological agents. With the exception of clofilium, which was designed to be a Class III agent, the Class III activity of the other agents was discovered after the compounds had been in use for other indications. 

As for amiodarone and bretylium, the Class III activity of sotalol (13) was discovered only after its initial development as a -blocking agent. The initial hypothesis, which led to the synthesis of sotalol as a )9-blocking agent. 

In addition to the amiodarone-related compounds, (81) and (82), described above, BASF has been exploring some novel heterocyclic compounds as Class III antiarrhythmic agents. A series of imidazo[l,2-c]pyrro-lo[l,2-a]quinazoline derivatives have been patented which are several times more potent than (-I- )-sotalol in lengthening QT interval of the electrocardiogram in the anaesthetized guinea-pig model [230], One of the most potent compounds is (85), which was 17-times more potent than the standard. These compounds represent one of the unique Class III structural types described to date. 

Commonly listed under a separate rubric (Class 111) are amiodarone and the P-blocking agent sotalol, which both inhibit K+-channels and which both cause marked prolongation of the AP with a lesser effect on Phase 0 rate of rise. 

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. 

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... 

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. 

The cornerstone of therapy for ventricular fibrillation is electrical deflbrillation. In the acute setting, defibrination is first-line therapy. Intravenous bretylium can occasionally contribute to conversion, but this is infrequent. In the management of out-of-hospital cardiac arrest, high-dose epinephrine (5 mg intravenously) improves the rate of successful resuscitation in patients with asystole, but not in those with ventricular fibrillation, when compared with the standard dose of 1 mg. Vasopressin (40 U intravenously) may more effective than 1 mg intravenous epinephrine in out-of-hospital patients with ventricular fibrillation that is resistant to electrical defibrillation. The OPTIC smdy (see Connolly et al., 2006) showed that amiodarone plus jS-blocker is superior than sotalol or jS-blocker alone for reducing ICD shocks in patients with reduced left ventricular function and history of sustained VT, VF, or cardiac arrest. 

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