What is the mechanism of action and primary use of verapamil (calcium channel blocker)?

Verapamil: Mechanism of Action and Clinical Uses

Verapamil is a non-dihydropyridine calcium channel blocker that inhibits L-type calcium channels in both cardiac and vascular smooth muscle, producing coronary and peripheral vasodilation, slowing AV nodal conduction, and reducing myocardial contractility—making it effective for hypertension, angina (particularly vasospastic), and supraventricular arrhythmias. 1

Mechanism of Action

Verapamil blocks the transmembrane influx of calcium ions through L-type (slow) calcium channels in arterial smooth muscle and cardiac cells, reducing intracellular calcium availability for muscle contraction 1, 2. This calcium antagonism produces several key effects:

• Vascular effects: Dilates main coronary arteries and peripheral arterioles, decreasing systemic vascular resistance and blood pressure without typically causing orthostatic hypotension or reflex tachycardia 1
• Cardiac conduction effects: Prolongs the effective refractory period within the AV node and slows AV conduction in a rate-related manner, making it highly effective for supraventricular tachyarrhythmias 1, 3
• Myocardial effects: Reduces myocardial contractility (negative inotropic effect) and decreases myocardial oxygen demand through reductions in afterload, contractility, and heart rate 2, 4
• Coronary vasodilation: Potently inhibits coronary artery spasm, whether spontaneous or ergonovine-induced, increasing myocardial oxygen delivery 1

Primary Clinical Uses

Hypertension

• Verapamil effectively lowers blood pressure by decreasing systemic vascular resistance through peripheral arterial vasodilation 1, 5
• Bradycardia (heart rate <50 bpm) is uncommon, occurring in only 1.4% of patients 1
• Particularly effective in older patients and those with low plasma renin activity 5
• Does not cause reflex tachycardia, orthostatic hypotension, or development of tolerance 5

Angina Pectoris

• Verapamil is highly effective for vasospastic (Prinzmetal's variant) angina due to its potent coronary artery vasodilatory and antispasm properties 1, 6
• Effective for unstable angina and chronic stable angina by reducing myocardial oxygen demand 2, 6
• The ACC/AHA guidelines note that verapamil may be used to control ongoing or recurring ischemia-related symptoms in patients already receiving adequate doses of nitrates and beta blockers, or in those unable to tolerate these agents 2

Supraventricular Arrhythmias

• Verapamil is 90% effective as the treatment of choice for uncomplicated paroxysmal supraventricular tachycardia 7
• Works by depressing AV nodal conduction through calcium channel blockade 3, 7

Important Clinical Considerations and Contraindications

Absolute Avoidance Situations

• Verapamil must be avoided in patients with pulmonary edema or evidence of severe left ventricular dysfunction 2, 4
• Retrospective analyses demonstrated detrimental effects on mortality in patients with LV dysfunction 2
• Should not be combined with beta-blockers in patients at risk for bradycardia or heart block 4

Critical Safety Warnings

• Verapamil can cause AV block even in patients without preexisting conduction defects 1
• In patients with sick sinus syndrome, verapamil may interfere with sinus-node impulse generation and induce sinus arrest or sinoatrial block 1
• Dangerous acceleration of ventricular rate and/or ventricular fibrillation has been reported in patients with atrial flutter or fibrillation and a coexisting accessory AV pathway (e.g., Wolff-Parkinson-White syndrome) 1

Common Side Effects

• Constipation is the most common side effect 3
• Hypotension, though usually without orthostatic changes 2
• Peripheral edema (similar to other calcium channel blockers) 4
• Dizziness and skin rash may occur 3

Pharmacokinetics

• Over 90% of oral verapamil is absorbed, but bioavailability is only 20-35% due to extensive first-pass hepatic metabolism 1
• Peak plasma concentrations occur 1-2 hours after oral administration 1
• Sustained-release formulations allow once-daily dosing with equivalent efficacy to conventional formulations given three times daily 5