Calcium Channel Blockers

Calcium channel blockers lower blood pressure by inhibiting L-type voltage-gated calcium channels, reducing calcium entry into vascular smooth muscle and cardiac cells. The dihydropyridines, such as amlodipine, act mainly on vascular smooth muscle to dilate arterioles, while the non-dihydropyridines, verapamil and diltiazem, also slow cardiac conduction and reduce contractility.

Definition

Calcium channel blockers are drugs that inhibit L-type voltage-gated calcium channels in vascular smooth muscle and cardiac tissue, reducing intracellular calcium and thereby lowering vascular tone, and in some subclasses cardiac rate and contractility.

Scope

This entry covers the pharmacology of L-type calcium channel inhibition, the contrast between vascular-selective dihydropyridines and rate-limiting non-dihydropyridines, and the outcome evidence supporting their use in hypertension. It is reference material, not prescribing guidance.

Core questions

• How does blocking L-type calcium channels relax vascular smooth muscle?
• What distinguishes dihydropyridine from non-dihydropyridine calcium channel blockers?
• What does outcome evidence show for calcium channel blockers in hypertension?

Key concepts

• L-type voltage-gated calcium channels
• Vascular smooth-muscle contraction and calcium
• Dihydropyridines (vascular-selective)
• Non-dihydropyridines (verapamil, diltiazem)
• Cardiac rate and contractility effects
• Reflex tachycardia and peripheral oedema

Mechanisms

Contraction of vascular smooth muscle and cardiac myocytes depends on calcium influx through L-type voltage-gated channels. Calcium channel blockers bind these channels and reduce calcium entry, relaxing arterial smooth muscle and lowering peripheral resistance. Dihydropyridines are relatively selective for vascular channels and produce arteriolar dilation with little direct cardiac depression, though the resulting fall in pressure can cause reflex tachycardia and ankle oedema. Non-dihydropyridines (verapamil, and to a lesser extent diltiazem) also act on cardiac calcium channels, slowing sinoatrial and atrioventricular nodal conduction and reducing contractility, which gives them additional rate-controlling effects.

Clinical relevance

Calcium channel blockers are a principal class for studying vascular smooth-muscle and cardiac calcium pharmacology and are widely examined in hypertension, including in older patients and in combination regimens. This entry describes mechanism and evidence as educational reference and does not provide dosing or treatment recommendations.

Evidence & guidelines

Major guidelines list calcium channel blockers among first-line antihypertensive classes, often favouring dihydropyridines for blood-pressure lowering and combination therapy. ALLHAT compared a calcium channel blocker with a diuretic and an ACE inhibitor, finding broadly similar major outcomes, and ASCOT-BPLA supported an amlodipine-based regimen over an atenolol-based one for cardiovascular events.

History

The cardiovascular actions of calcium antagonists were characterised in the 1960s and 1970s, with verapamil, nifedipine, and diltiazem emerging as prototypes of distinct chemical classes. Longer-acting dihydropyridines such as amlodipine later became prominent antihypertensive agents, and large outcome trials defined their comparative role.

Seminal works

• allhat-2002
• dahlof-2005

Frequently asked questions

What is the difference between dihydropyridine and non-dihydropyridine calcium channel blockers?

Dihydropyridines such as amlodipine act mainly on vascular smooth muscle to dilate arteries, while non-dihydropyridines such as verapamil and diltiazem also act on the heart, slowing conduction and reducing contractility.

Why can calcium channel blockers cause ankle swelling?

Dihydropyridines dilate precapillary arterioles more than venules, raising capillary pressure and promoting fluid movement into tissue, which can produce peripheral oedema.