Calcium channel blockers

Calcium channel blockers

Calcium channel blockers are used to treat hypertension and angina. Verapamil is used to treat some tachyarrhythmias. Calcium channel blockers are also used in the treatment of Raynaud's phenomenon.

The dihydropyridine calcium channel blocker nifedipine has been used as a co-analgesic to relieve smooth muscle spasm (eg hiccups, oesophageal spasm). Nifedipine has also been used as a tocolytic.

Mechanism of action

Calcium channel blockers inhibit entry of calcium ions through a subset of voltage-sensitive calcium channels, and thus impair contraction and cause smooth muscle relaxation. In the heart, some calcium channel blockers are also negatively inotropic and dromotropic.

Calcium channel blockers are classified as dihydropyridines or nondihydropyridines. The nondihydropyridines are further divided into phenylalkylamines and benzothiazepines. Each acts on a specific receptor on the calcium channel and has a different profile of pharmacological activity.

Dihydropyridines

Dihydropyridine calcium channel blockers currently available in Australia are amlodipine, felodipine, nifedipine, lercanidipine and nimodipine. They act to reduce peripheral resistance, generally without clinically significant cardiodepression. Nimodipine is indicated for the management of subarachnoid haemorrhage and is discussed in Drugs used in cerebrovascular disease.

Short-acting dihydropyridine formulations produce flushing and headache, and in chronic use can be associated with increased risk of cardiac events in patients at high cardiovascular risk. Adverse symptoms can be largely avoided by the use of controlled-release formulations, which are not strongly associated with risk in these patients. Amlodipine and lercanidipine have longer elimination half-lives and do not require controlled-release formulations. All dihydropyridine calcium channel blockers can cause dependent oedema that does not respond to diuretics, and may require dosage reduction or withdrawal of the drug.

Nondihydropyridines

Phenylalkylamines

Verapamil is less active as an arteriolar vasodilator than the dihydropyridines but blocks the slow inward calcium current in cardiac tissues as well as smooth muscle. It is well absorbed from the gut, but there is extensive first-pass hepatic extraction, which is why parenteral doses are much lower than equipotent oral ones. Half-life after a single dose is only 2 to 7 hours but this increases considerably on repeated administration. Sustained-release formulations permit once-daily dosing.

Verapamil may cause bradycardia, limit exercise-induced increase in heart rate and reduce the force of cardiac contraction. Verapamil can exacerbate systolic heart failure. It often causes constipation. Combination with beta blockers is not recommended, due to an increased risk of heart block and hypotension.

Benzothiazepines

Diltiazem reduces calcium influx in both smooth muscle and cardiac tissue, but affects the latter relatively less than verapamil. Diltiazem is well absorbed from the gut and disappears from plasma with a half-life of 3 to 4.5 hours. Sustained-release formulation permits once-daily dosing for hypertension.