Calcium Channel Blockers Used for Hypertension
Long-acting dihydropyridine calcium channel blockers are recommended first-line agents for treating hypertension, including amlodipine, nifedipine (extended-release), and felodipine, along with non-dihydropyridine CCBs like diltiazem and verapamil. 1
Types of Calcium Channel Blockers
Dihydropyridine CCBs
- Amlodipine: 5-10 mg once daily; long-acting with peripheral arterial vasodilation effects; commonly used first-line agent 2
- Nifedipine: Extended-release formulation 30-90 mg daily; should only be used in long-acting form for hypertension 3
- Felodipine: 5-10 mg once daily; long-acting with primarily vascular effects 1
- Isradipine: 2.5-10 mg twice daily; medium duration of action 1
- Nicardipine: 20-40 mg three times daily; short duration of action 1
- Nisoldipine: 20-40 mg once daily; short duration of action 1
- Nitrendipine: 20 mg once or twice daily; medium duration of action 1
- Lercanidipine: A third-generation CCB with comparable efficacy to amlodipine but with less peripheral edema 4
Non-Dihydropyridine CCBs
- Diltiazem: Extended-release 120-360 mg once daily; affects both vascular smooth muscle and cardiac conduction 1
- Verapamil: Extended-release 120-480 mg once daily; has significant effects on cardiac conduction and contractility 1, 5
Mechanism of Action
- CCBs inhibit calcium ion influx across cell membranes in vascular smooth muscle and cardiac muscle 2, 3
- This leads to peripheral arterial vasodilation, reduced peripheral vascular resistance, and consequently lower blood pressure 2
- Dihydropyridine CCBs have more pronounced effects on vascular smooth muscle than on cardiac conduction 1, 5
- Non-dihydropyridine CCBs (verapamil, diltiazem) have more significant effects on cardiac conduction and contractility 1
Clinical Use in Hypertension
- CCBs are recommended as first-line agents for hypertension treatment by major guidelines 1
- They can be used as monotherapy or in combination with other antihypertensive drugs 1
- Particularly effective in:
Combination Therapy
- CCBs are often combined with ACE inhibitors or ARBs for enhanced efficacy 1
- Combination with ACE inhibitors or ARBs reduces the incidence of peripheral edema 4
- In patients with diabetes and albuminuria, ACE inhibitors or ARBs are preferred first-line, with CCBs as add-on therapy 1
- For resistant hypertension, a combination of a diuretic, CCB, and ACE inhibitor/ARB is recommended, with consideration of adding a mineralocorticoid receptor antagonist if needed 1
Side Effects and Precautions
- Common side effects:
- Precautions:
Special Populations
- Pregnancy: Long-acting nifedipine can be used for hypertension in pregnancy when needed 1
- Diabetes: CCBs are effective but may be second-line to ACE inhibitors/ARBs in patients with albuminuria 1
- Coronary Artery Disease: Both dihydropyridine and non-dihydropyridine CCBs are effective for patients with hypertension and stable ischemic heart disease 1
- Pulmonary Hypertension: CCBs (particularly nifedipine, diltiazem, and amlodipine) may be used in selected patients who demonstrate vasoreactivity 1
Clinical Pearls
- Long-acting formulations are preferred over short-acting ones to avoid rapid fluctuations in blood pressure 1
- Dihydropyridine CCBs can be safely combined with beta-blockers, which can mitigate reflex tachycardia 1
- Third-generation CCBs like lercanidipine may cause less peripheral edema than earlier generations 4
- CCBs do not negatively impact glucose metabolism or lipid profiles, making them suitable for patients with metabolic disorders 7, 6