10.6

Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers

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Class IV antiarrhythmic drugs block open or inactivated voltage-sensitive L-type Ca²⁺ channels.

Their actions are use-dependent and prevent repolarization until dissociating from the channel, decreasing the phase 4 depolarization rate.

This slows the SA and AV nodes' conduction, lengthens the effective refractory period, and decreases the heart rate. Together, these actions suppress ectopic beats.

Class IV drugs include nondihydropyridines, like verapamil and diltiazem.

Verapamil, the prototype drug of this class, is a racemic mixture with the ʟ-enantiomer having a greater inhibitory effect on calcium ion influx. It causes PR interval prolongation.

Intravenously administered, verapamil causes adverse effects like bradycardia and extracardiac effects like hypotension and peripheral edema. So, it is usually administered orally to reduce side effects.

Diltiazem shares similarities with verapamil but tends to cause less bradycardia.

Class IV agents are commonly used to treat re-entrant supraventricular tachycardia and to decrease the ventricular rate in atrial flutter and fibrillation.

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Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.

Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and peripheral arteries, reducing the force of cardiac contraction. Verapamil also slows conduction in the SA and AV nodes, decreasing heart rate. Diltiazem is similar to verapamil but has more impact on smooth muscle and causes less bradycardia. Both drugs can control SVT and manage the ventricular rate in atrial flutter/fibrillation. Adverse effects may include bradycardia, hypotension, and peripheral edema. It is important to note that calcium channel blockers have different effects on different tissues. Dihydropyridines like nifedipine mainly block calcium channels in vascular smooth muscle, leading to an increased heart rate due to sympathetic activation. Verapamil, diltiazem, and bepridil block calcium channels in cardiac cells, slowing the heart rate and prolonging the PR interval. Caution should be exercised using verapamil and diltiazem for ventricular tachycardia, as the risk of adverse effects is higher. Oral administration of these drugs generally results in milder side effects than bolus administration. Verapamil is prescribed as a racemate, with the L-enantiomer being more potent but subjected to first-pass hepatic metabolism when taken orally. Verapamil and diltiazem can increase serum digoxin concentration, which may excessively slow the ventricular response in patients with atrial fibrillation. Close monitoring of patients' heart conditions and drug interactions is necessary.

Although class IV antiarrhythmic drugs are used to manage SVT and atrial flutter/fibrillation, they show adverse effects, including bradycardia, hypotension, and peripheral edema. Caution should be exercised when using these drugs; careful monitoring is required for drug interactions.

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