10.4: Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers

Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β₂-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which indirectly block calcium channels and counteract this catecholamine-induced stimulation. Their action mechanism primarily involves depressing phase 4 of cardiac depolarization, reducing automaticity, prolonging AV conduction, and decreasing both heart rate and contractility. As a result, these drugs effectively prevent atrial flutter ventricular tachycardia and terminate reentrant arrhythmias. Class II drugs display variations in β₁-selectivity, intrinsic sympathomimetic activity, membrane-stabilizing effects, and action potential prolongation. β-blockers are classified as selective or nonselective based on their affinity for a particular adrenoceptor subtype. Nonselective β-blockers, such as propranolol, inhibit catecholamine-mediated hypokalemia and block sodium ion channels. However, due to their actions on the β₂-adrenoceptors, they may induce bronchospasm. Conversely, β₁-selective drugs like metoprolol exhibit reduced bronchospastic effects, making them more versatile for various therapeutic applications.

Other selective molecules are esmolol, a short-acting intravenous drug for emergencies; acebutolol, effective in treating ventricular ectopic beats; and sotalol, known for its additional potassium ion channel-blocking properties.

Despite their effectiveness, Class II drugs may cause adverse effects, including fatigue, bradycardia, bronchospasm, and hypotension. Furthermore, abrupt discontinuation of these drugs can lead to rebound symptoms, potentially exacerbating arrhythmias. It is essential to closely monitor patients on these medications and gradually taper the dosage when discontinuing treatment. Although generally well-tolerated, Class II antiarrhythmic drugs are considered less effective than Class I alternatives for specific types of arrhythmias.

β-adrenergic stimulation increases intracellular Ca²⁺ influx and pacemaker currents, leading to arrhythmias. Class II antiarrhythmic drugs are β-adrenoceptor antagonists that indirectly block Ca²⁺ channels to counteract β receptor stimulation.

These drugs primarily depress phase 4 cardiac depolarization, reducing automaticity, prolonging AV conduction, and decreasing heart rate and contractility.

Class II drugs vary in β₁-selectivity, intrinsic sympathomimetic activity, membrane-stabilizing effects, and action potential prolongation.

Nonselective β-blockers, such as propranolol, inhibit β₂ -receptor-mediated hypokalemia and also block Na⁺ channels. However, they can cause bronchospasm.

β₁ -selective drugs like metoprolol have reduced bronchospastic effects.

Other class II drugs include esmolol, a short-acting intravenous drug, and acebutolol, used to treat ventricular ectopic beats.

Adverse effects of class II drugs include fatigue, bradycardia, bronchospasm, and hypotension. Abrupt discontinuation of these drugs can cause rebound symptoms, potentially worsening arrhythmias.