Calcium Channel Antagonists
Examples
Dihydropyridines
- Nifedipine (m/r)
- Amlodipine
- Felodipine (m/r)
- Nimodipine
- Diltiazem
- Verapamil
Indications
- Hypertension
- Prophylaxis of angina/angina treatment
- Verapamil is used in the treatment of some arrhythmias
- Nimodipine is used for the prevention of ischaemic neurological deficits following subarachnoid haemorrhage
Diltiazem 2% cream is also used unlicensed for the treatment of anal fissures.
Contraindications
Contraindications:
- Aortic stenosis
- Non-dihydropyridines are contraindicated in patients with bradyarrhythmias and heart failure
- Avoid after recent myocardial infarction
- Hepatic impairment
Mechanism
Calcium channel antagonists block the L-type voltage sensitive calcium channels on the myocardium, vascular and smooth muscle cells. The Dihydropyridine calcium channel blockers have a vasodilatory action and have no effect on the on cardiac contractility or conduction. In comparison, Verapamil and Diltiazem (to a lesser degree) are poor vasodilators but depress cardiac conduction and contractility.
The vasodilatation action of the Dihydropyridines has the effect of reducing venous return which in turn reduces left ventricular work load.
Administration
Oral (verapamil and diltiazem are available as intravenous preparations).
The brand of diltiazem and nifedipine must be stated on the prescription as each brand has varying bioavailability.
The brand of diltiazem and nifedipine must be stated on the prescription as each brand has varying bioavailability.
Adverse Reactions
The main side effects are caused by widespread vasodilatation:
Dihydropyridines can cause gum hyperplasia.
Verapamil and Diltiazem may cause worsening of heart failure and heart block / bradycardia.
Verapamil may cause constipation.
- Flushing
- Dizziness
- Hypotension
- Ankle swelling (note this is not due to oedema)
- Headache
Dihydropyridines can cause gum hyperplasia.
Verapamil and Diltiazem may cause worsening of heart failure and heart block / bradycardia.
Verapamil may cause constipation.
Interactions
All types of calcium channel blockers (but not all individual drugs) can increase plasma Digoxin and Ciclosporin concentrations, which may precipitate toxicity.
All calcium channel blockers will potentiate the action of other hypotensive agents.
Verapamil and Diltiazem should not be prescribed with beta blockers as this may cause significant reduction in heart rate and a fall in cardiac output. Similar issues can occur with Amiodarone.
Both Verapamil and Diltiazem can increase the risk of myositis if given with statins.
All calcium channel blockers can be involved in drug-drug (and drug-food) interactions via the cytochrome P450 system. Possible interactions should be checked prior to prescribing.
All calcium channel blockers will potentiate the action of other hypotensive agents.
Verapamil and Diltiazem should not be prescribed with beta blockers as this may cause significant reduction in heart rate and a fall in cardiac output. Similar issues can occur with Amiodarone.
Both Verapamil and Diltiazem can increase the risk of myositis if given with statins.
All calcium channel blockers can be involved in drug-drug (and drug-food) interactions via the cytochrome P450 system. Possible interactions should be checked prior to prescribing.
Education
Inform any patient who is treated with a Dihydropyridine calcium channel blockers to avoid grapefruit juice.
Warn the patient about the side effects of ankle swelling and headaches.
Warn the patient about the side effects of ankle swelling and headaches.
Pharmacokinetics
The metabolism of Dihydropyridines (except Amlodipine) and Verapamil is affected by grapefruit juice and other enzyme inhibitors.
