Dihydropyridine Calcium Channel Blockers

Dihydropyridine calcium channel blockers relax arteriolar smooth muscle by blocking L-type channels, lowering blood pressure and coronary resistance with little effect on conduction or contractility. They are first-line antihypertensives, particularly in older patients and people of African ancestry.

Members. Amlodipine, felodipine, lercanidipine, lacidipine, nifedipine, nicardipine, nimodipine, isradipine, nisoldipine and clevidipine.

Mechanism. Arteriolar vasodilation lowers systemic vascular resistance. Reflex sympathetic activation can cause tachycardia, especially with short-acting formulations. Nimodipine crosses the blood-brain barrier and relaxes cerebral vessels.

Pharmacokinetics. Amlodipine has slow onset and half-life of 30 to 50 hours, which gives smooth once-daily control and tolerance of missed doses. Nifedipine immediate release acts within minutes with abrupt effects. Modified release preparations avoid peaks. Nicardipine and clevidipine are intravenous. Most are metabolised by CYP3A4.

Oedema. Dose-related ankle oedema comes from pre-capillary dilation, not fluid retention. It does not respond to diuretics and is reduced by adding an ACE inhibitor or angiotensin receptor blocker.

• Amlodipine: once daily; most widely used.
• Nifedipine: modified release for hypertension and angina; immediate release only for selected uses; Raynaud phenomenon and pregnancy hypertension.
• Felodipine, lercanidipine, lacidipine: once daily; lercanidipine causes less oedema.
• Nicardipine: intravenous for hypertensive emergencies and perioperative hypertension.
• Nimodipine: subarachnoid haemorrhage.
• Clevidipine: ultra short acting intravenous.

• Hypertension: amlodipine 5 mg daily, increased to 10 mg (2.5 mg in frail patients and mild hepatic impairment); nifedipine modified release 30 mg daily, increased to 90 mg; felodipine 5 mg daily to 10 mg (maximum 20 mg); lercanidipine 10 mg daily to 20 mg.
• Angina and vasospasm: amlodipine 5 to 10 mg daily; nifedipine modified release 30 to 60 mg daily.
• Hypertension in pregnancy: nifedipine modified release 10 to 20 mg twice daily, maximum 40 mg twice daily. For severe hypertension, nifedipine immediate release 10 mg orally, repeated after 20 to 30 minutes as needed. Do not use the sublingual route.
• Hypertensive emergency: nicardipine infusion 5 mg/hour, increased by 2.5 mg/hour every 5 to 15 minutes to a maximum of 15 mg/hour.
• Subarachnoid haemorrhage: nimodipine 60 mg orally every 4 hours for 21 days, or 30 mg every 2 hours if hypotension develops. Never inject the oral capsule contents intravenously; give by nasogastric tube if needed.
• Raynaud phenomenon: nifedipine modified release 30 to 60 mg daily.
• Selection: use amlodipine or nifedipine modified release as monotherapy in older patients and patients of African ancestry. Pair with an ACE inhibitor or angiotensin receptor blocker, or with a thiazide-like diuretic.

Contraindications. Cardiogenic shock, unstable angina and acute myocardial infarction (immediate release nifedipine), severe aortic stenosis (relative), and for amlodipine severe hypotension.

Adverse effects. Ankle oedema, flushing, headache, palpitations, dizziness, gingival hyperplasia, rash, abdominal pain and, with immediate release nifedipine, abrupt hypotension with reflex tachycardia, myocardial ischaemia and stroke.

Interactions. Clarithromycin, azoles, ritonavir and grapefruit juice raise levels. Rifampicin, carbamazepine and phenytoin lower nifedipine markedly. Simvastatin should not exceed 20 mg daily with amlodipine. Ciclosporin and tacrolimus levels rise. Magnesium sulfate with nifedipine can add hypotension and neuromuscular weakness.

Monitoring. Blood pressure and heart rate, oedema, and gingival health.

Referral and escalation. Severe hypotension, chest pain or stroke symptoms after a short-acting dose need urgent assessment.

Special groups. Pregnancy: nifedipine and amlodipine are used. Breastfeeding: nifedipine and amlodipine are compatible. Hepatic impairment: start at the lowest dose. Older adults: lower starting dose with careful titration. Children: amlodipine 2.5 to 5 mg daily for ages 6 to 17 years.