What are class two antiarrhythmic agents?

Class II Antiarrhythmic Agents

Class II antiarrhythmic agents are beta-adrenergic receptor blockers (beta-blockers), which work by blocking sympathetic stimulation of the heart. 1

Mechanism of Action

Beta-blockers exert their antiarrhythmic effects through multiple mechanisms:

• Antisympathetic action by blocking beta-adrenergic receptors, reducing the effects of catecholamines on cardiac tissue 2
• Suppression of automaticity in cardiac pacemaker cells, particularly those with enhanced sympathetic activity 3
• Slowing of AV nodal conduction, which is particularly useful for rate control in supraventricular arrhythmias 1
• Reduction of ventricular fibrillation threshold, providing protection against life-threatening arrhythmias 4
• Prevention of catecholamine-induced arrhythmias, especially in settings of myocardial ischemia or infarction 3

Clinical Applications

Rate Control in Atrial Fibrillation

• IV beta-blockers are drugs of choice (Class IIa, LOE A) for acute rate control in most patients with atrial fibrillation and rapid ventricular response 1
• Beta-blockers are more effective than digoxin during exercise for rate control 1
• The combination of digoxin and beta-blockers may be more effective than beta-blockers alone 1

Ventricular Arrhythmias

• Beta-blockers reduce sudden death in heart failure patients (Level of Evidence A) 1
• In polymorphic VT associated with myocardial ischemia, beta-blockers may reduce the frequency of arrhythmia recurrence (Class IIb, LOE C) 1
• Beta-blockers have demonstrated potent antiarrhythmic effects in postinfarction trials and congestive heart failure studies 4

Pregnancy

• Digoxin, a beta-blocker, or a nondihydropyridine calcium channel antagonist is recommended to control ventricular response in pregnant patients with AF 1
• Metoprolol and propranolol are generally considered safe but should be avoided in the first trimester when possible 1
• Beta-blockers should not be taken in the first trimester if possible, though they are categorized as Class C drugs (sotalol is Class B, atenolol is Class D) 1

Common Beta-Blockers Used as Antiarrhythmics

• Propranolol - non-selective beta-blocker 5
• Metoprolol - cardioselective beta-blocker 1
• Atenolol - cardioselective beta-blocker 6
• Sotalol - unique beta-blocker with additional Class III properties (potassium channel blockade) 1, 7

Important Contraindications and Precautions

Absolute Contraindications

• Beta-blockers are contraindicated (Class III, LOE C) in patients with obstructive lung disease who develop AF 1
• Should not be used in patients with severe bradycardia or high-degree AV block without pacemaker protection 6

Drug Interactions

• Amiodarone combined with beta-blockers has additive negative chronotropic effects 5, 6
• Calcium channel blockers (verapamil, diltiazem) combined with beta-blockers can cause significant bradycardia, heart failure, and cardiovascular collapse 5
• Disopyramide with beta-blockers has been associated with severe bradycardia, asystole, and heart failure 6
• Catecholamine-depleting drugs (reserpine) may have additive effects, causing hypotension and marked bradycardia 5, 6

Special Populations

• Use with caution in patients with impaired hepatic or renal function 5, 6
• Patients with peripheral arterial circulatory disorders may experience aggravation of symptoms 6
• Patients with history of severe anaphylactic reactions may be more reactive to allergens and unresponsive to usual doses of epinephrine while on beta-blockers 5, 6

Advantages Over Other Antiarrhythmic Classes

• Beta-blockers are generally safe agents that do not normally require therapeutic drug monitoring 2
• Unlike Class I antiarrhythmic drugs, beta-blockers reduce mortality in patients with structural heart disease 7, 8
• Beta-blockers reduce morbidity and may lower mortality in patients with moderate to severe heart failure 8
• Side effects are often dose-related and can be minimized by using optimal minimal effective doses 3