nondihydropyridine CCBs

Nondihydropyridine CCBs block L-type calcium channels in cardiac myocytes and, to a lesser extent, vascular smooth muscle. Verapamil has the greatest negative inotropic and chronotropic effect, followed by diltiazem, which has more balanced cardiac and vascular effects. Mechanism: inhibition of calcium influx during phase 2 of the cardiac action potential slows conduction through the AV node (increasing AV nodal refractory period) and decreases SA node automaticity, making them effective for rate control in atrial fibrillation/flutter and termination of AV nodal reentrant tachycardia (AVNRT). They also reduce myocardial oxygen demand by decreasing contractility and afterload, useful in angina.

Clinical uses: hypertension, angina (including vasospastic/Prinzmetal angina), rate control in AF/flutter, SVT, and hypertrophic cardiomyopathy (verapamil helps reduce outflow obstruction and improve diastolic filling).

Adverse effects: bradycardia, AV block, constipation (especially verapamil), gingival hyperplasia, and negative inotropy leading to worsened heart failure in patients with reduced ejection fraction. Contraindicated with concurrent beta-blocker use in patients with pre-existing conduction disease due to risk of severe bradycardia or heart block. Also contraindicated in WPW syndrome with atrial fibrillation (can accelerate conduction through accessory pathway, precipitating ventricular fibrillation).

Key distinction from dihydropyridine CCBs (e.g., amlodipine, nifedipine): dihydropyridines are more selective for vascular smooth muscle, causing peripheral vasodilation with reflex tachycardia, whereas nondihydropyridines have significant direct cardiac effects (rate and conduction slowing) with less vasodilation and no significant reflex tachycardia.

Pharmacokinetics: verapamil is a strong CYP3A4 substrate/inhibitor, leading to significant drug interactions (e.g., increased digoxin, statin levels). Diltiazem also inhibits CYP3A4 but to a lesser extent.