Calcium channel blockers

Key examples

• Amlodipine
• Nifedipine
• Diltiazem
• Verapamil

 

Common indications

• Amlodipine and, to a lesser extent, nifedipine are used for the first- or second-line treatment of hypertension, to reduce the risk of stroke, myocardial infarction and death from cardiovascular disease.
• All calcium channel blockers can be used to control symptoms in people with stable angina; β-blockers are the main alternative.
• Diltiazem and verapamil are used to control cardiac rate in people with supraventricular arrhythmias including supraventricular tachycardia, atrial flutter and atrial fibrillation.

 

Mechanisms of action

• Calcium channel blockers decrease Ca2+ entry into vascular and cardiac cells, reducing intracellular calcium concentration. This causes relaxation and vasodilation in arterial smooth muscle, lowering arterial pressure. In the heart, calcium channel blockers reduce myocardial contractility. They suppress cardiac conduction, particularly across the atrioventricular (AV) node, slowing ventricular rate. Reduced cardiac rate, contractility and afterload reduce myocardial oxygen demand, preventing angina. Calcium channel blockers can broadly be divided into two classes. Dihydropyridines, including amlodipine and nifedipine, are relatively selective for the vasculature, whereas non-dihydropyridines are more selective for the heart. Of the non-dihydropyridines, verapamil is the most cardioselective, whereas diltiazem also has some effects on the vessels.

 

Important adverse effects

• Common adverse effects of amlodipine and nifedipine include ankle swelling, flushing, headache and palpitations, which are caused by vasodilatation and compensatory tachycardia. 
• Verapamil commonly causes constipation and less often, but more seriously, can cause bradycardia, heart block and cardiac failure. As diltiazem has mixed vascular and cardiac actions, it can cause any of these adverse effects.

 

Warnings

• Verapamil and diltiazem should be used with caution in patients with poor left ventricular function as they can precipitate or worsen heart failure. They should generally be avoided in people with AV nodal conduction delay in whom they may provoke complete heart block. Amlodipine and nifedipine should be avoided in patients with unstable angina as vasodilatation causes a reflex increase in contractility and tachycardia, which increases myocardial oxygen demand. In patients with severe aortic stenosis, amlodipine and nifedipine should be avoided as they can provoke collapse.

 

Important interactions

• Non-dihydropyridine calcium channel blockers (verapamil and diltiazem) should not be prescribed with β-blockers except under close specialist supervision. Both drug classes are negatively inotropic and chronotropic, and together may cause heart failure, bradycardia, and even asystole.