CCBs

Calcium channel blockers (CCBs) are a class of medications that inhibit L-type voltage-gated calcium channels, reducing calcium influx into vascular smooth muscle and cardiac myocytes. By limiting intracellular calcium, they cause arterial vasodilation and, with non-dihydropyridines, a reduction in heart rate and AV nodal conduction. CCBs are divided into two main groups: dihydropyridines (DHPs) and non-dihydropyridines (non-DHPs).

DHPs, such as amlodipine, felodipine, nifedipine, and isradipine, primarily dilate peripheral arteries and decrease systemic vascular resistance. Non-DHPs, including verapamil and diltiazem, act on both the heart and vessels and tend to slow heart rate and AV conduction more than DHPs.

Common indications include hypertension and angina (stable and vasospastic). Non-DHPs are also used for rate control in certain arrhythmias (eg, atrial fibrillation or flutter with rapid ventricular response). Some CCBs are employed for migraine prophylaxis and for Raynaud phenomenon, though these uses vary by agent and patient.

Contraindications include significant hypotension, cardiogenic shock, and certain types of heart block without a pacemaker. Caution is advised when combining CCBs with beta blockers or other negative inotropic agents due to additive effects on heart rate and conduction. Drug interactions are common; CCBs are metabolized by cytochrome P450 enzymes (notably 3A4), affecting many other drugs such as statins and digoxin. Grapefruit juice can elevate levels of some CCBs, particularly dihydropyridines.

Adverse effects vary by subclass. DHPs frequently cause edema and flushing; non-DHPs can cause bradycardia, constipation (especially verapamil), and conduction abnormalities. In heart failure, amlodipine and felodipine are generally preferred over non-DHPs when a CCB is indicated.

History: CCBs were developed in the late 20th century following discoveries in calcium channel physiology, providing a major addition to cardiovascular pharmacotherapy.