Introduction

Calcium channel blockers (CCBs) were developed in the 1970s and are now widely used.

Dihydropyridine calcium channel blockers (drugs ending in 'pine')

Reduce systemic vascular resistance and arterial pressure. Examples include:

• Nifedipine - has more affinity for vascular smooth muscle and less for other sites. Hence it's value in Raynaud's disease. It rarely precipitates heart failure, as negative inotropic effects are offset by reduction in afterload. Longer-acting preparations should only be used for angina (rarely) and hypertension.
• Nicardipine - is similarly effective on smooth muscle and used for angina prophylaxis and hypertension. It is not licensed for use in Raynaud's disease.
• Amlodipine and felodipine - similarly, do not adversely affect myocardial contractility (with the risk of heart failure) and have a longer duration of action than nifedipine, making them useful in hypertension and angina. All are valuable in angina associated with coronary vasospasm. Side-effects relate to vasodilatation and may improve after a few days (headache, flushing).
• Isradipine, lacidipine and lercanidipine - again, are similar in effect to nifedipine but are only indicated for hypertension.
• Nimodipine - is similar to nifedipine but has an enhanced, selective effect on the cerebral arteries. This makes it useful for cerebral artery spasm and it is used solely for this purpose after subarachnoid haemorrhage (to prevent ischaemic deficit).

Phenylalkylamine calcium channel blockers

Used in angina and effects include reduced myocardial oxygen demand and reversal of coronary vasospasm with minimal peripheral vasodilation. Examples include:

• Verapamil - is very negatively inotropic, impairs atrioventricular conduction, so slowing heart rate and lowering blood pressure. As a consequence it is used for angina, hypertension and supraventricular tachycardias (SVTs) but can also precipitate heart failure, cause hypotension, exacerbate conduction disorders and is contra-indicated with beta blockers.

Benzothiazepine calcium channel blockers

Intermediate between above 2 and has both cardio-depressant and vasodilatory effects. Examples include:

• Diltiazem - is effective in angina and the longer-acting formulation in hypertension. It is less negatively inotropic than verapamil but should still be used cautiously with beta blockers.

Indications

• Angina
• Hypertension
• Raynaud's Phenomenon (separate article)
• Supraventricular arrhythmias
• Ischaemic neurological deficit after subarachnoid haemorrhage
• Prophylaxis for cluster headache

Evidence of efficacy

• Angina:
  • Consensus that CCBs are effective in reducing symptoms in stable angina.
  • No significant differences compared with beta blockers in frequency of angina, exercise duration, mortality, quality of life.^1,2,3
  • No significant difference compared with isosorbide mononitrate in frequency of attacks or quality of life, but peripheral oedema more of a problem.⁴
• Hypertension:
  • Lowering blood pressure prevents strokes and ischaemic heart disease.⁵ CCBs are a key therapeutic choice in the major guidelines for the treatment of hypertension.
• Raynaud's disease:
  • Nifedipine and diltiazem are the mainstay of medical treatment.
  • Nifedipine has been shown consistently to reduce frequency and severity of attacks in primary Raynaud's disease but is associated with expected adverse effects (see below).^6,7,8 In one typical study 19 out of 21 sufferers preferred nifedipine to placebo but 30% reported side-effects.⁷
  • The evidence base for amlodipine and diltiazem is not strong.
• Supraventricular arrhythmias:
  • Intravenous verapamil and diltiazem have been found equally effective at reducing heart rate at 10 or 30 minutes compared with placebo in atrial flutter and atrial fibrillation but use of verapamil could be limited by hypotension.^9,10
• Cluster headache:
  • Verapamil is used (unlicensed indication) to help reduce the severity of cluster attacks and there seems consensus from patient groups and clinicians that it is useful. It has been reported to cause bradycardia and atrioventricular block so further research is needed.¹¹

Common adverse effects

These can be predicted from the type of CCB and mode of action, as already illustrated. Examples include:

• Myocardial effects:
  • Hypotension
  • Heart failure
• Conduction effects:
  • Heart block
  • Arrhythmias
• Vascular smooth muscle:
  • Flushing
  • Oedema
  • Headaches
  • Rashes
• Other effects:
  • Constipation
  • Rashes
  • Gynaecomastia
  • Photosensitivity

Cautions and contra-indications

Again, these can be predicted from the type of CCB and mode of action. Individual drug monographs need to be reviewed. Some examples include:

• Cardiovascular: shock, unstable angina, significant aortic stenosis, bradycardia, heart failure, etc.
• Avoidance of grapefruit juice with felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine and verapamil. This may affect metabolism.
• Sudden withdrawal of CCBs may exacerbate angina - see separate article Angina Pectoris.

These are best considered under each individual drug.

Monitoring and follow-up

This will be determined largely by the condition being treated. Blood pressure and electrocardiography monitoring may be warranted but are best decided upon an individual basis.