Calcium channel blockers (CCBs) are used in the treatment of many cardiovascular conditions including hypertension and angina. They are divided into subclasses, non-dihydropyridines and dihydropyridines and differ by their pharmacokinetic properties, clinical uses, response, and selectivity.
The non-dihydropyridine CCBs do not end in the suffix ‘-ine’ hinted by the name of the subclass, non-dihydropyridines. They cause more cardiac depression and less vasodilation than dihydropyridine CCBs resulting in a reduction in heart rate and cardiac contractility.
Dihydropyridine CCBs end in the suffix ‘-ine’ and have more vascular selectivity and fewer cardiac effects. They act primarily as peripheral vasodilators and are used in the treatment of hypertension and angina. They do not suppress AV node conduction or SA node automaticity.
Mechanism of Action:
The name of this class, calcium channel blockers, hints at its mechanism of action – inhibits the entry of calcium into cells of the cardiac and peripheral vascular smooth muscles.
- Calcium entry into L-type channels of cardiac and peripheral vascular cells is needed for them to contract or constrict more strongly.
- By blocking calcium entry, calcium channel blockers cause
- peripheral vascular smooth muscle relaxation (decreases blood pressure)
- decreased myocardial contractility (decrease myocardial demand making them effective in angina)
- decrease heart rate and conduction velocity (useful in arrhythmias).
The main side effects of calcium channel blockers are hypotension and dizziness which is related to their effects on vasodilation so it is easier for you to memorize.
In addition, they can also cause the following side effects by subclass:
- Constipation, gingival hyperplasia, worsening cardiac output, and bradycardia.
- Peripheral edema, headache, flushing
- Non-dihydropyridines are contraindicated in patients with decompensated heart failure, second or third-degree AV blockade, and sick sinus syndrome due to their inhibitory effects on the SA and AV node, slowing cardiac conduction and contractility.
- Monitor patients for hypotension, edema, and bradycardia.
- Peripheral edema is dose-dependent and may occur within 2 to 3 weeks of initiating calcium channel blocker therapy, particularly dihydropyridines. Peripheral edema due to the redistribution of fluid from the intravascular space to the interstitium.
- Diphydroyridines can cause reflex tachycardia and acute hypotension due to their potent vasodilating effects. This effect is more common with first-generation short-acting dihydropyridines (e.g. immediate-release nifedipine) and less with newer agents that are longer acting (e.g. amlodipine). The effect may be lessened by using sustained-release formulations.
- Diltiazem decreases AV node conduction and heart rate to a lesser extent than verapamil but these drugs should be monitored closely for bradycardia especially with patients on beta-blockers.
- Verapamil and diltiazem are considered moderate cytochrome P450 3A4 enzyme inhibitors and should be monitored for drug interactions.
- Constipation is a more common side effect with verapamil and occurs to a lesser extent with diltiazem.
- McKeever RG, Hamilton RJ. Calcium Channel Blockers. [Updated 2020 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482473/
- Maclaughlin EJ, Saseen JJ. Hypertension. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. eds. Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw-Hill.