Calcium channel blockers

Calcium channel blockers (CCBs) are drugs that bind to and block the L-type calcium channel. The L-type channels are the predominant calcium channels in the myocardium and the vascular smooth muscles. By blocking these channels, CCBs cause peripheral arterial vasodilation and myocardial depression, which leads to a drop in blood pressure and negative chronotropic, inotropic, and dromotropic effects on the myocardium. The most common indications for CCB use are hypertension, angina, and supraventricular arrhythmias. CCBs are also beneficial in the treatment of cardiomyopathy, thromboangiitis obliterans, Raynaud's phenomenon, and cluster headaches. CCBs are divided into three classes based on their effects: dihydropyridines (e.g., nifedipine, amlodipine) are potent vasodilators, phenylalkylamines (verapamil, gallopamil) are potent myocardial depressants, and benzothiazepines (diltiazem) are moderate vasodilators and myocardial depressants. The main side effects of dihydropyridines are caused by vasodilation (headaches, peripheral edema, reflex tachycardia), and those of phenylalkylamines by myocardial depression (bradyarrhythmias, atrioventricular block). The side effects of benzothiazepines are generally similar but milder compared to those of the other CCB classes. CCBs are contraindicated in patients with pre-existing cardiac conduction disorders (e.g., atrioventricular block, sick sinus syndrome), symptomatic hypotension, and acute coronary syndrome.

Class of CCB		Examples	Effects
Dihydropyridines [1][2]		Short-acting : nifedipine, clevidipine Medium-acting : nitrendipine, nicardipine, lercanidipine Long-acting : amlodipine	Potent vasodilator Minimal myocardial depressant activity
Non-dihydropyridine CCBs	Benzothiazepines	Diltiazem	Moderate vasodilator Moderate myocardial depressant activity
	Phenylalkylamines	Verapamil Gallopamil	Less potent vasodilator than dihydropyridines Potent myocardial depressant

References:^[3]

• CCBs bind to and block L-type calcium channels → decreased frequency of Ca²⁺ channel opening in response to cell membrane depolarization → decreased transmembrane Ca²⁺ current
• Effects of decreased Ca²⁺ influx
  • Vascular smooth muscle relaxation → vasodilation → decreased peripheral vascular resistance → decreased afterload → decreased blood pressure
  • Decreased cardiac muscle contractility (negative inotropic action) → decreased cardiac output → decreased blood pressure
  • Decreased SA node discharge rate (negative chronotropic action) → decreased heart rate (bradycardia) → decreased cardiac output → decreased blood pressure
  • Decreased AV node conduction (negative dromotropic action) → termination of supraventricular arrhythmias

Dihydropyridine CCBs (e.g., nifedipine, amlodipine) primarily act on vascular smooth muscles. Nondihydropyridine CCBs (diltiazem < verapamil) primarily act on the heart.

References:^[4][5]

Dihydropyridines	Effects due to vasodilation Peripheral edema (esp. amlodipine) Headaches, dizziness Facial flushing, feeling feverish Reflex tachycardia (esp. nifedipine) May worsen symptoms of angina Gingival hyperplasia
Benzothiazepines	Side effects similar to the other classes of CCBs, but milder
Phenylalkylamines	Reduced contractility/bradyarrhythmia and drug-induced atrioventricular block Constipation

Phenylalkylamines (verapamil) primarily affect the calcium channels of the heart and are contraindicated in cases of heart failure because of their negative effect on myocardial contractility!
References:^{[6][7][8][9][10][11][12]}

We list the most important adverse effects. The selection is not exhaustive.

• Common indications for CCBs
  • Arterial hypertension (esp. amlodipine)
  • Angina (all CCBs except for nifedipine)
    • Stable angina (for patients with contraindications or who are not responsive to β blockers)
    • Vasospastic angina (variant or Prinzmetal's angina)
  • Supraventricular arrhythmias (esp. verapamil and diltiazem
    • Supraventricular tachycardia
    • Atrial fibrillation
• Less common indications
  • Cardiomyopathy
  • Raynaud's phenomenon
  • Thromboangiitis obliterans
  • Cluster headache
  • Achalasia

References:^[13]

• All classes of CCB
  • Allergy/hypersensitivity to CCBs
  • Symptomatic hypotension
  • Acute coronary syndrome
• Dihydropyridines
  • Hypertrophic obstructive cardiomyopathy (HOCM)
  • Severe stenotic heart valve defects
• Benzothiazepines and phenylalkylamines
  • Pre-existing cardiac conduction disorders
    • Wolff-Parkinson-White syndrome
    • Sick sinus syndrome
    • Systolic dysfunction (in congestive heart failure)
    • Bradycardia
    • Second or third-degree atrioventricular block
  • Combination with beta blockers → risk of AV block

References:^{[14][6][7][15][16][17][18][19][20][21][22][23]}

We list the most important contraindications. The selection is not exhaustive.