What is the mechanism of action (MOA) of Sotalol?

Mechanism of Action of Sotalol

Sotalol has a dual mechanism of action, combining both beta-adrenoreceptor blocking (Vaughan Williams Class II) and cardiac action potential duration prolongation (Vaughan Williams Class III) antiarrhythmic properties. 1

Primary Pharmacological Effects

• Sotalol is a racemic mixture of d- and l-sotalol isomers, with both isomers having similar Class III antiarrhythmic effects, while the l-isomer is responsible for virtually all of the beta-blocking activity 1
• The beta-blocking effect is non-cardioselective, reaching half-maximal effect at about 80 mg/day and maximal effect at doses between 320 and 640 mg/day 1
• Significant Class III electrophysiological effects are seen only at daily doses of 160 mg and above in adults 1

Electrophysiological Effects

• Class II (Beta-Blockade) Effects:

  • Increased sinus cycle length (slowed heart rate) 1
  • Decreased AV nodal conduction 1
  • Increased AV nodal refractoriness 1

• Class III Effects:

  • Prolongs the plateau phase of the cardiac action potential by inhibiting the delayed rectifier potassium current 1, 2
  • Has lesser effect on the inward rectifying potassium current 2
  • Little to no effect on the inward calcium or sodium currents 2
  • Prolongs atrial and ventricular monophasic action potentials 1
  • Increases effective refractory period of atrial muscle, ventricular muscle, and atrio-ventricular accessory pathways in both anterograde and retrograde directions 1

ECG Effects

• With oral doses of 160 to 640 mg/day, sotalol produces dose-related mean increases of 40-100 msec in QT interval and 10-40 msec in QTc interval 1
• In patients with atrial fibrillation/flutter, mean increases in QT intervals of 25 msec, 40 msec, and 54 msec were found in the 80 mg, 120 mg, and 160 mg dose groups, respectively 1
• No significant alteration in QRS interval is observed 1

Antiarrhythmic Properties

• Sotalol exerts a potent antifibrillatory action modulated by its antiadrenergic effects 2
• It suppresses premature ventricular contractions and nonsustained ventricular tachycardia 2
• Prevents inducible ventricular tachycardia and fibrillation in patients with advanced structural heart disease 2
• In patients with implanted defibrillators, sotalol reduces the average defibrillatory threshold to 6 joules compared to a mean of 16 joules for patients primarily receiving amiodarone 1

Clinical Implications and Cautions

• Sotalol is devoid of partial agonist or membrane stabilizing activity 1
• The drug is primarily eliminated by the kidneys with a mean elimination half-life of 12 hours 3
• Sotalol should be used cautiously in patients with renal insufficiency due to risk of drug accumulation and proarrhythmia 4
• Torsades de pointes may develop in conjunction with excessive prolongation of the QT interval due to bradycardia, hypokalemia, or high plasma concentrations of the drug 5
• If prescribed, sotalol therapy should be initiated only in a monitored setting with daily measurement of the QT interval from a 12-lead ECG 4

Sotalol's unique combination of beta-blocking and action potential prolonging properties makes it effective for a broad spectrum of arrhythmias, but requires careful monitoring due to its potential for causing bradycardia and QT prolongation.