verapamil

Verapamil blocks L-type calcium channels in cardiac and vascular smooth muscle, but has greater selectivity for cardiac tissue compared to dihydropyridines (e.g., amlodipine, nifedipine). By inhibiting calcium influx into SA and AV nodal cells, it slows conduction velocity and prolongs the refractory period at the AV node (negative dromotropy), decreases heart rate (negative chronotropy), and reduces myocardial contractility (negative inotropy). It also causes vascular smooth muscle relaxation, reducing systemic vascular resistance and afterload.

Clinical uses: (1) Rate control in atrial fibrillation/flutter, (2) termination and prophylaxis of paroxysmal supraventricular tachycardia (PSVT) involving the AV node (e.g., AVNRT), (3) treatment of variant (Prinzmetal) angina and stable angina, (4) hypertension, (5) hypertrophic cardiomyopathy (reduces outflow obstruction).

Pharmacokinetics: Extensively metabolized by CYP3A4, significant first-pass metabolism, and can inhibit CYP3A4 and P-glycoprotein leading to important drug interactions (e.g., increased digoxin, statin, and cyclosporine levels).

Adverse effects: Constipation is classic and common. Others include bradycardia, AV block, hypotension, peripheral edema, and heart failure exacerbation due to negative inotropy. Contraindicated in patients with WPW syndrome with atrial fibrillation (may paradoxically increase conduction through accessory pathway, leading to ventricular fibrillation), severe LV dysfunction, sick sinus syndrome, or AV block without pacemaker.

Key caution: Concomitant use with beta-blockers can cause severe bradycardia, AV block, or cardiogenic shock due to additive negative chronotropic/dromotropic/inotropic effects—an important boards testable interaction.

Mechanistic distinction: Verapamil > Diltiazem > Dihydropyridines in cardiac selectivity; dihydropyridines are more selective for vascular smooth muscle and used primarily for hypertension without significant AV nodal effects.