Calcium Channel Blocker Uses

## Overview

Calcium channel blockers (CCBs) inhibit L-type voltage-gated calcium channels, reducing calcium entry into vascular smooth muscle and cardiac cells. The two subclasses, dihydropyridines (DHPs) and non-dihydropyridines (non-DHPs), have markedly different tissue selectivity and clinical profiles.

## Dihydropyridines

Amlodipine, nifedipine, felodipine, and lercanidipine preferentially act on vascular smooth muscle, causing arterial vasodilation with minimal direct cardiac effects. Amlodipine is the most prescribed CCB globally due to its 30-50 hour half-life allowing once-daily dosing, consistent BP reduction, and tolerability. Peripheral edema (dose-dependent, up to 10%) is the main limitation and results from precapillary arteriolar dilation without compensatory venodilation. Combining with an ACE inhibitor or ARB reduces edema by dilating the postcapillary venules.

## Non-Dihydropyridines

Verapamil and diltiazem act on both vascular smooth muscle and cardiac tissue, producing vasodilation plus negative chronotropy, negative inotropy, and negative dromotropy. They slow AV nodal conduction and are effective for supraventricular tachycardia and AF rate control. Verapamil is the more potent negative inotrope and chronotrope; diltiazem is intermediate. Both are contraindicated in systolic heart failure (HFrEF) due to their cardiodepressant effects.

## Hypertension

CCBs are effective across all demographics and are particularly useful in elderly patients and Black patients, populations in which RAAS inhibitors may be less effective as monotherapy. The ALLHAT trial confirmed amlodipine's cardiovascular efficacy comparable to chlorthalidone. CCBs are metabolically neutral, not affecting glucose, lipids, or electrolytes.

## Angina

DHPs reduce afterload and dilate coronary arteries. Non-DHPs additionally reduce heart rate and contractility. For vasospastic (Prinzmetal) angina, CCBs are the treatment of choice. Long-acting formulations are essential; short-acting nifedipine causes reflex tachycardia and is associated with adverse outcomes.

## Arrhythmias

Verapamil and diltiazem are first-line for terminating AV nodal reentrant tachycardia (AVNRT) when vagal maneuvers and adenosine fail. For AF rate control, they are alternatives to beta-blockers, especially when beta-blockers are contraindicated (e.g., severe reactive airway disease). IV diltiazem is commonly used in the emergency department for rapid AF rate control.

## Drug Interactions

Verapamil and diltiazem inhibit CYP3A4 and P-glycoprotein. They increase plasma levels of digoxin (40-60%), simvastatin, cyclosporine, and tacrolimus. Combining with beta-blockers increases the risk of symptomatic bradycardia and AV block, though the combination (DHP + beta-blocker) is often safe and effective for angina.

## Key Takeaways

- DHPs are primarily vasodilators; non-DHPs also slow heart rate and contractility
- Amlodipine's long half-life and efficacy make it the most prescribed CCB
- Non-DHPs are contraindicated in HFrEF due to negative inotropic effects
- Verapamil and diltiazem have significant CYP3A4-mediated drug interactions