Calcium channel blockers: classification, mechanism of action and indications

This post is an overview on calcium channel blockers, in this first part we will discuss their classification, mechanism of action as well as clinical indications.

Classification of agents

Chemical classification of calcium channel blockers

Classification of calcium channel blockers

Calcium channel blockers comprise three chemical groups, all of them bind the L-type Ca++ channel, but each class binds to different binding sites of the same channel:

  • Phenilalkylamines: verapamil is the only drug in this group, it binds to the V binding site.
  • Benzothiazepines: diltiazem binds to the D binding site in the L-type Ca++ channel. It shows cardiovascular effects similar to those of verapamil.
  • Dihydropyridines: the prototype agent in this group is nifedipine, a first generation dihydropyridine that binds to the N binding site. Second generation agents include isradipine, nicardipine, and felodipine. Amlodipine is considered a third generation dihydropyridine.

Mechanism of action and pharmacological effects

Image credit: Novel Vascular Biology of Third-Generation L-Type Calcium Channel Antagonists: Ancillary Actions of Amlodipine. R.P. Mason et al. 2003;23;2155-2163; Arterioscler Thromb Vasc Biol

Calcium channel antagonists block the inward movement of calcium by binding to the L-type calcium channels in the heart and in smooth muscle of the peripheral vasculature. CCB’s dilate coronary arteries and peripheral arterioles, but not veins. They also decrease cardiac contractility (negative inotropic effect) ,automaticity at the SA node and conduction at the AV node. Dilation of the coronary arteries increases myocardial oxigen supply.

As the following table shows, there are differences in terms of tissue selectivity between dihydropiridines (nifedipine and others), diltiazem and verapamil:

Peripheral and coronary vasodilation Depression of cardiac contractility Depression of SA node Depression of AV node
Nifedipine +++++ + + 0
Diltiazem +++ ++ +++++ ++++
Verapamil ++++ ++++ +++++ +++++
Effects of CCB on heart contraction and conduction

Effects of CCBs on heart contraction and conduction

Dihydropiridines have minimal effect on cardiac conduction or heart rate, while they have potent actions as arteriolar vasodilators. This class of drugs can cause reflex tachycardia when peripheral vasodilation is marked.

On the other hand, verapamil and diltiazem slow AV conduction and decrease SA node automaticity, they also decrease heart rate. Diltiazem is used in the treatment of variant angina because of its coronary antispasmodic properties.

Indications

Dihydropiridines indications

Dihydropiridines indications

Hypertension

CCB’s  effectiveness in the treatment of hypertension is  related to a decrease in peripheral resistance accompanied by increases in cardiac index.

CCB are also useful in the treatment of hypertensive patients with comorbidities such as: asthma, diabetes, angina, ond or peripheral vascular disease.

Angina pectoris

Calcium channel blockers act as coronary vasodilators, producing variable and dose-dependent reductions in myocardial oxygen demand, contractility, and arterial pressure. These combined pharmacologic effects are advantageous and make these agents as effective as beta blockers in the treatment of angina pectoris. They are indicated when beta blockers are contraindicated, poorly tolerated, or ineffective.

In the presence of heart failure, the use of calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect.

Supraventricular tachyarrhythmias

Verapamil and diltiazem indications

Verapamil and diltiazem indications

Verapamil and diltiazem are class IV antiarrhythmics, according to Vaughan and Williams’ classification of antiarrhythmic drugs. This is based on their depressant action at the SA and AV nodes. Their ability to inhibit the AV node is employed in the management of supraventricular tachyarrhythmias, such as: atrial fibrillation, atrial flutter and paroxysmal supraventricular tachycardia.

Video review on calcium channel blockers

The following video summarizes most of the concepts above discussed:

References and further reading

Lullmann, Heinz; Mohr Klaus. “Color Atlas of Pharmacology”, 3rd edition. Thieme: 2005.

Fauci AS, Kasper DL, Braunwald E, Hauser SL, Longo DL, Jameson JL, LOscalzo J: “Harrison’s Principles of Internal Medicine”, 17th edition. Mc Graw Hill Medical: 2008.

Golan, David E (editor). “Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy”, 2nd edition. LWW: 2008.

Katzung, B. “Basic & Clinical Pharmacology”, 10th Edition. Mc Graw Hill Medical: 2007


Calcium channel blockers act as coronary vasodilators, producing variable and dose-dependent reductions in myocardial oxygen demand, contractility, and arterial pressure. These combined pharmacologic effects are advantageous and make these agents as effective as beta blockers in the treatment of angina pectoris. They are indicated when beta blockers are contraindicated, poorly tolerated, or ineffective.

In the presence of heart failure, the use of calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect.

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