UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Major side effects and safety of calcium channel blockers

Authors
Michael J Bloch, MD, FACP, FASH, FSVM, FNLA
Jan Basile, MD
Section Editors
George L Bakris, MD
Norman M Kaplan, MD
Deputy Editor
John P Forman, MD, MSc

INTRODUCTION

Calcium channel blockers are widely used in the treatment of hypertension, angina pectoris, cardiac arrhythmias, and other disorders. The longer-acting preparations have been prescribed with increasing frequency. According to recommendations from the Eighth Joint National Committee (JNC 8) members, calcium channel blockers are a recommended choice for initial management of hypertension, either as monotherapy or as part of antihypertensive combination therapy. There are robust data suggesting that their use reduces the risk of subsequent cardiovascular events [1]. In addition, some meta-analyses have suggested that calcium channel blockers may be more effective than other drugs in reducing stroke risk [2-6]. (See "Choice of drug therapy in primary (essential) hypertension".)

A review of the major side effects associated with these agents and the controversy concerning their effect on coronary events, mortality, gastrointestinal bleeding, and the development of cancer are presented here. The management of calcium channel intoxication is presented separately. (See "Calcium channel blocker poisoning".)

TYPES OF CALCIUM CHANNEL BLOCKERS

While all approved calcium channel blockers inhibit the L-type calcium channel on cells, they are divided into two major categories based upon their predominant physiologic effects: the dihydropyridines, which are predominantly vasodilators and generally have chronotropic and inotropic effects, and the non-dihydropyridines, which are less potent vasodilators and also slow cardiac contractility and conduction [7].

Dihydropyridines — The dihydropyridines, including nifedipine, isradipine, felodipine, nicardipine, nisoldipine, lacidipine, and amlodipine, are potent vasodilators that have little or no negative effect upon cardiac contractility or conduction. They are typically used to treat hypertension and chronic stable angina. Different agents and preparations have different durations of action. Longer-acting agents are generally safer and are increasingly preferred.

Non-dihydropyridines — The non-dihydropyridines, including verapamil and diltiazem, are used in the management of hypertension, chronic stable angina, and cardiac arrhythmias. They are somewhat less potent vasodilators compared with dihydropyridines, but they have a greater depressive effect on cardiac conduction and contractility. (See "Calcium channel blockers in the treatment of cardiac arrhythmias".)

           

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jul 2017. | This topic last updated: Feb 14, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014; 311:507.
  2. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013; 31:1281.
  3. Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA 2003; 290:2805.
  4. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288:2981.
  5. Lubsen J, Wagener G, Kirwan BA, et al. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with symptomatic stable angina and hypertension: the ACTION trial. J Hypertens 2005; 23:641.
  6. Hart P, Bakris GL. Calcium antagonists: Do they equally protect against kidney injury? Kidney Int 2008; 73:795.
  7. Triggle DJ. Drug targets in the voltage-gated calcium channel family: why some are and some are not. Assay Drug Dev Technol 2003; 1:719.
  8. Pedrinelli R, Dell'Omo G, Mariani M. Calcium channel blockers, postural vasoconstriction and dependent oedema in essential hypertension. J Hum Hypertens 2001; 15:455.
  9. Abernethy DR, Schwartz JB. Calcium-antagonist drugs. N Engl J Med 1999; 341:1447.
  10. Makani H, Bangalore S, Romero J, et al. Peripheral edema associated with calcium channel blockers: incidence and withdrawal rate--a meta-analysis of randomized trials. J Hypertens 2011; 29:1270.
  11. van Hamersvelt HW, Kloke HJ, de Jong DJ, et al. Oedema formation with the vasodilators nifedipine and diazoxide: direct local effect or sodium retention? J Hypertens 1996; 14:1041.
  12. Pedrinelli R, Dell'Omo G, Melillo E, Mariani M. Amlodipine, enalapril, and dependent leg edema in essential hypertension. Hypertension 2000; 35:621.
  13. Makani H, Bangalore S, Romero J, et al. Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema. Am J Med 2011; 124:128.
  14. Weir MR, Rosenberger C, Fink JC. Pilot study to evaluate a water displacement technique to compare effects of diuretics and ACE inhibitors to alleviate lower extremity edema due to dihydropyridine calcium antagonists. Am J Hypertens 2001; 14:963.
  15. de Vries RJ, van Veldhuisen DJ, Dunselman PH. Efficacy and safety of calcium channel blockers in heart failure: focus on recent trials with second-generation dihydropyridines. Am Heart J 2000; 139:185.
  16. Furberg CD, Psaty BM, Meyer JV. Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. Circulation 1995; 92:1326.
  17. Psaty BM, Heckbert SR, Koepsell TD, et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA 1995; 274:620.
  18. Li CI, Daling JR, Tang MT, et al. Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Intern Med 2013; 173:1629.
  19. Pahor M, Guralnik JM, Salive ME, et al. Do calcium channel blockers increase the risk of cancer? Am J Hypertens 1996; 9:695.
  20. Pahor M, Guralnik JM, Ferrucci L, et al. Calcium-channel blockade and incidence of cancer in aged populations. Lancet 1996; 348:493.
  21. Bangalore S, Kumar S, Kjeldsen SE, et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. Lancet Oncol 2011; 12:65.
  22. Grimaldi-Bensouda L, Klungel O, Kurz X, et al. Calcium channel blockers and cancer: a risk analysis using the UK Clinical Practice Research Datalink (CPRD). BMJ Open 2016; 6:e009147.
  23. Pahor M, Guralnik JM, Furberg CD, et al. Risk of gastrointestinal haemorrhage with calcium antagonists in hypertensive persons over 67 years old. Lancet 1996; 347:1061.
  24. Kizer JR, Kimmel SE. Epidemiologic review of the calcium channel blocker drugs. An up-to-date perspective on the proposed hazards. Arch Intern Med 2001; 161:1145.
  25. He Y, Chan EW, Leung WK, et al. Systematic review with meta-analysis: the association between the use of calcium channel blockers and gastrointestinal bleeding. Aliment Pharmacol Ther 2015; 41:1246.