Calcium-channel blockers (CCBs) were developed in the 1970s and are now widely used.
- Cells of the myocardium (negative inotropic effect/myocardial depression).
- Cells within the His-Purkinje system of the heart (impairment of atrioventricular conduction).
- Cells of vascular smooth muscle (dilatation of coronary and peripheral arteries).
Because the various drugs differ in the relative affinity for these sites, a different balance of therapeutic effects is seen and hence differing indications, efficacy, contra-indications and side-effects. There are three subclasses of CCB:
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Dihydropyridine calcium-channel blockers
- 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, these 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
These are 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, and 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
These are intermediate between the above two and have 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.
- Raynaud's phenomenon
- Supraventricular tachycardias
- Ischaemic neurological deficit after subarachnoid haemorrhage
- Prophylaxis for cluster headache
Evidence of efficacy
- 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.
- No significant difference, compared with isosorbide mononitrate, in frequency of attacks or quality of life, but peripheral oedema more of a problem.
- Lowering blood pressure prevents strokes and ischaemic heart disease. CCBs are a key therapeutic choice in the major guidelines for the treatment of hypertension.
- Nifedipine and diltiazem are the mainstay of medical treatment.
- Nifedipine has been shown to reduce frequency and severity of attacks in primary Raynaud's disease but is associated with expected adverse effects (see 'Common adverse effects', below).
- The evidence base for amlodipine and diltiazem is not strong.
- 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.
- 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.
Common adverse effects
These can be predicted from the type of CCB and mode of action, as already illustrated. Examples include:
- Heart failure
- Heart block
Vascular smooth muscle:
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.
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.
Further reading & references
- Abrams J; Clinical practice. Chronic stable angina. N Engl J Med. 2005 Jun 16;352(24):2524-33.
- Angina; NICE CKS, May 2012
- Hypertension - not diabetic; NICE CKS, April 2012
- Management of Acute Coronary Syndromes (ACS) in patients presenting without persistent ST-segment elevation, European Society of Cardiology (2011)
- Hall R, Chong C; A double-blind, parallel-group study of amlodipine versus long-acting nitrate in the management of elderly patients with stable angina. Cardiology. 2001;96(2):72-7.
- Lawes CM, Bennett DA, Feigin VL, et al; Blood pressure and stroke: an overview of published reviews. Stroke. 2004 Apr;35(4):1024.
- Pope JE; Raynaud's phenomenon (primary). Clin Evid (Online). 2011 Mar 14;2011. pii: 1119.
- Supraventricular Arrhythmias, European Society of Cardiology Guideline (2003)
- Siu CW, Lau CP, Lee WL, et al; Intravenous diltiazem is superior to intravenous amiodarone or digoxin for achieving ventricular rate control in patients with acute uncomplicated atrial fibrillation. Crit Care Med. 2009 Jul;37(7):2174-9; quiz 2180.
- Cohen AS, Matharu MS, Goadsby PJ; Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy. Neurology. 2007 Aug 14;69(7):668-75.
|Original Author: Dr Richard Draper||Current Version: Dr Gurvinder Rull||Peer Reviewer: Dr Helen Huins|
|Last Checked: 11/03/2013||Document ID: 178 Version: 8||© EMIS|
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