nondihydropyridine

Non-dihydropyridine CCBs include verapamil and diltiazem. Unlike dihydropyridines (e.g., amlodipine, nifedipine), which act predominantly on peripheral vascular smooth muscle causing vasodilation, non-dihydropyridines act more on the heart—slowing conduction through the AV node and decreasing myocardial contractility and heart rate. Mechanism: they bind L-type calcium channels in cardiac nodal tissue, decreasing calcium influx, which slows SA node automaticity and prolongs AV node conduction (increasing AV nodal refractory period), useful for rate control in atrial fibrillation/flutter and terminating AV nodal reentrant tachycardia (verapamil is used acutely for PSVT). They also reduce myocardial oxygen demand, making them useful in stable angina and vasospastic (Prinzmetal) angina. Clinically important adverse effects include bradycardia, AV block, constipation (especially verapamil), and negative inotropy—so they must be used cautiously or avoided in patients with systolic heart failure (HFrEF) and should not be combined with beta-blockers due to risk of severe bradycardia/heart block. They are contraindicated in Wolff-Parkinson-White syndrome with atrial fibrillation because blocking the AV node can paradoxically increase conduction through the accessory pathway, leading to ventricular fibrillation. Verapamil has greater cardiac selectivity and constipating effect; diltiazem has intermediate effects between verapamil and dihydropyridines. Drug interactions: both are substrates/inhibitors of CYP3A4, increasing levels of statins, and can increase digoxin levels. Overdose management includes IV calcium, glucagon, and insulin-dextrose (hyperinsulinemia-euglycemia therapy) for severe CCB toxicity.