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Chapter: Basic & Clinical Pharmacology : Agents Used in Cardiac Arrhythmias

Calcium Channel-Blocking Drugs (Class 4)

These drugs, of which verapamil is the prototype, were first intro-duced as antianginal agents.

CALCIUM CHANNEL-BLOCKING DRUGS (CLASS 4)

These drugs, of which verapamil is the prototype, were first intro-duced as antianginal agents. Verapamil and diltiazem also have antiarrhythmic effects. The dihydropyridines (eg, nifedipine) do not share anti-arrhythmic efficacy and may precipitate arrhythmias.

VERAPAMIL

Cardiac Effects

Verapamil blocks both activated and inactivated L-type calcium channels. Thus, its effect is more marked in tissues that fire fre-quently, those that are less completely polarized at rest, and those in which activation depends exclusively on the calcium current, such as the SA and AV nodes. AV nodal conduction time and effective refractory period are consistently prolonged by therapeu-tic concentrations. Verapamil usually slows the SA node by its direct action, but its hypotensive action may occasionally result in a small reflex increase of SA rate.

Verapamil can suppress both early and delayed afterdepolariza-tions and may antagonize slow responses arising in severely depo-larized tissue.

Extracardiac Effects

Verapamil causes peripheral vasodilation, which may be beneficial in hypertension and peripheral vasospastic disorders. Its effects on smooth muscle produce a number of extracardiac effects .

Toxicity

Verapamil’s cardiotoxic effects are dose-related and usually avoid-able. A common error has been to administer intravenous vera-pamil to a patient with ventricular tachycardia misdiagnosed as supraventricular tachycardia. In this setting, hypotension and ventricular fibrillation can occur. Verapamil’s negative inotropic effects may limit its clinical usefulness in diseased hearts . Verapamil can induce AV block when used in large doses or in patients with AV nodal disease. This block can be treated with atropine and β-receptor stimulants.Adverse extracardiac effects include constipation, lassitude, nervousness, and peripheral edema.

Pharmacokinetics & Dosage

The half-life of verapamil is approximately 7 hours. It is exten-sively metabolized by the liver; after oral administration, its bio-availability is only about 20%. Therefore, verapamil must be administered with caution in patients with hepatic dysfunction or impaired hepatic perfusion.

In adult patients without heart failure or SA or AV nodal dis-ease, parenteral verapamil can be used to terminate supraventricu-lar tachycardia, although adenosine is the agent of first choice. Verapamil dosage is an initial bolus of 5 mg administered over 2–5 minutes, followed a few minutes later by a second 5 mg bolus if needed. Thereafter, doses of 5–10 mg can be administered every 4–6 hours, or a constant infusion of 0.4 mcg/kg/min may be used.

Effective oral dosages are higher than intravenous dosage because of first-pass metabolism and range from 120 mg to 640 mg daily, divided into three or four doses.

Therapeutic Use

Supraventricular tachycardia is the major arrhythmia indication for verapamil. Adenosine or verapamil are preferred over older treatments (propranolol, digoxin, edrophonium, and vasocon-strictor agents) and cardioversion for termination. Verapamil can also reduce the ventricular rate in atrial fibrillation and flutter. It only rarely converts atrial flutter and fibrillation to sinus rhythm. Verapamil is occasionally useful in ventricular arrhythmias. However, intravenous verapamil in a patient with sustained ven-tricular tachycardia can cause hemodynamic collapse.


DILTIAZEM

Diltiazem appears to be similar in efficacy to verapamil in the management of supraventricular arrhythmias, including rate con-trol in atrial fibrillation. An intravenous form of diltiazem is avail-able for the latter indication and causes hypotension or bradyarrhythmias relatively infrequently.


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