Skip to main content
NCBI home page
The Western Journal of Medicine logoLink to The Western Journal of Medicine
. 1982 Jul;137(1):24–31.

Calcium Channel Blockers

Prakash C Deedwania 1
PMCID: PMC1273979  PMID: 6291255

Abstract

Calcium (Ca++) plays an essential role in many cardiovascular physiologic processes. Electrophysiologic properties of the sinus and atrioventricular nodes greatly depend on Ca++ ion influx. Also, Ca++ is the main link for excitation-contraction coupling of the myocardium. Ca++ channel blockers are a group of heterogeneous compounds that block the ionic influx of Ca++ into the myocardial and vascular smooth muscle cells. Because Ca++ plays a central role, it is not surprising that Ca++ channel blockers can produce profound alterations in cardiovascular functions. Recently several studies have shown these agents to be useful in the treatment of supraventricular tachyarrhythmia, variant angina, chronic stable angina and hypertrophic cardiomyopathy. In the future they may be found useful in preserving myocardium during cardiopulmonary bypass, in limiting infarct size and in the treatment of hypertension and congestive heart failure.

Full text

PDF
24

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antman E., Muller J., Goldberg S., MacAlpin R., Rubenfire M., Tabatznik B., Liang C. S., Heupler F., Achuff S., Reichek N. Nifedipine therapy for coronary-artery spasm. Experience in 127 patients. N Engl J Med. 1980 Jun 5;302(23):1269–1273. doi: 10.1056/NEJM198006053022301. [DOI] [PubMed] [Google Scholar]
  2. Carmeliet E., Vereecke J. Adrenaline and the plateau phase of the cardiac action potential. Importance of Ca++, Na+ and K+ conductance. Pflugers Arch. 1969;313(4):300–315. doi: 10.1007/BF00593955. [DOI] [PubMed] [Google Scholar]
  3. Ellrodt G., Chew C. Y., Singh B. N. Therapeutic implications of slow-channel blockade in cardiocirculatory disorders. Circulation. 1980 Oct;62(4):669–679. doi: 10.1161/01.cir.62.4.669. [DOI] [PubMed] [Google Scholar]
  4. Fleckenstein A. Die Zügelung des Myocardstoffwechsels durch Verapamil. Angriffspunkte und Anwendungsmöglighkeiten. Arzneimittelforschung. 1970 Sep;20(Suppl):1317+–1317+. [PubMed] [Google Scholar]
  5. Fleckenstein A., Kammermeier H., Döring H. J., Freund H. J. Zum Wirkungsmechanismus neuartiger Koronardilatatoren mit gleichzeitig Sauerstoff-einsparenden Myokard-Effekten, Prenylamin und Iproveratril. 1. Z Kreislaufforsch. 1967 Jul;56(7):716–744. [PubMed] [Google Scholar]
  6. Fleckenstein A. Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu Rev Pharmacol Toxicol. 1977;17:149–166. doi: 10.1146/annurev.pa.17.040177.001053. [DOI] [PubMed] [Google Scholar]
  7. Folts J. D., Crowell E. B., Jr, Rowe G. G. Platelet aggregation in partially obstructed vessels and its elimination with aspirin. Circulation. 1976 Sep;54(3):365–370. doi: 10.1161/01.cir.54.3.365. [DOI] [PubMed] [Google Scholar]
  8. Fondacaro J. D., Han J., Yoon M. S. Effects of verapamil on ventricular rhythm during acute coronary occlusion. Am Heart J. 1978 Jul;96(1):81–86. doi: 10.1016/0002-8703(78)90129-1. [DOI] [PubMed] [Google Scholar]
  9. Freedman B., Dunn R. F., Richmond D. R., Kelly D. T. Coronary artery spasm during exercise: treatment with verapamil. Circulation. 1981 Jul;64(1):68–75. doi: 10.1161/01.cir.64.1.68. [DOI] [PubMed] [Google Scholar]
  10. Ginsburg R., Bristow M. R., Harrison D. C., Stinson E. B. Studies with isolated human coronary arteries. Some general observations, potential mediators of spasm, role of calcium antagonists. Chest. 1980 Jul;78(1 Suppl):180–186. [PubMed] [Google Scholar]
  11. Heupler F. A., Jr, Proudfit W. L. Nifedipine therapy for refractory coronary arterial spasm. Am J Cardiol. 1979 Oct 22;44(5):798–803. doi: 10.1016/0002-9149(79)90200-5. [DOI] [PubMed] [Google Scholar]
  12. Hossack K. F., Bruce R. A. Improved exercise performance in persons with stable angina pectoris receiving diltiazem. Am J Cardiol. 1981 Jan;47(1):95–101. doi: 10.1016/0002-9149(81)90296-4. [DOI] [PubMed] [Google Scholar]
  13. Johnson S. M., Mauritson D. R., Corbett J. R., Woodward W., Willerson J. T., Hillis L. D. Double-blind, randomized, placebo-controlled comparison of propranolol and verapamil in the treatment of patients with stable angina pectoris. Am J Med. 1981 Sep;71(3):443–451. doi: 10.1016/0002-9343(81)90180-7. [DOI] [PubMed] [Google Scholar]
  14. Kaltenbach M., Hopf R., Kober G., Bussmann W. D., Keller M., Petersen Y. Treatment of hypertrophic obstructive cardiomyopathy with verapamil. Br Heart J. 1979 Jul;42(1):35–42. doi: 10.1136/hrt.42.1.35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Katz A. M., Reuter H. Cellular calcium and cardiac cell death. Am J Cardiol. 1979 Jul;44(1):188–190. doi: 10.1016/0002-9149(79)90270-4. [DOI] [PubMed] [Google Scholar]
  16. Kimura E., Kishida H. Treatment of variant angina with drugs: a survey of 11 cardiology institutes in Japan. Circulation. 1981 Apr;63(4):844–848. doi: 10.1161/01.cir.63.4.844. [DOI] [PubMed] [Google Scholar]
  17. Klein H. O., Pauzner H., Di Segni E., David D., Kaplinsky E. The beneficial effects of verapamil in chronic atrial fibrillation. Arch Intern Med. 1979 Jul;139(7):747–749. [PubMed] [Google Scholar]
  18. Kohlhardt M., Bauer B., Krause H., Fleckenstein A. Differentiation of the transmembrane Na and Ca channels in mammalian cardiac fibres by the use of specific inhibitors. Pflugers Arch. 1972;335(4):309–322. doi: 10.1007/BF00586221. [DOI] [PubMed] [Google Scholar]
  19. Kohlhardt M., Fleckenstein A. Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium. Naunyn Schmiedebergs Arch Pharmacol. 1977 Jul;298(3):267–272. doi: 10.1007/BF00500899. [DOI] [PubMed] [Google Scholar]
  20. Krikler D. M., Spurrell R. A. Verapamil in the treatment of paroxysmal supraventricular tachycardia. Postgrad Med J. 1974 Jul;50(585):447–453. doi: 10.1136/pgmj.50.585.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. LINDNER E. [N-(3-phenylisopropyl)-3,3-diphenylpropylamine, a new substance with a dilating action on the coronary vessels. Part 1: Action on the circulation]. Arzneimittelforschung. 1960 Aug;10:569–573. [PubMed] [Google Scholar]
  22. Langer G. A. Heart: excitation-contraction coupling. Annu Rev Physiol. 1973;35:55–86. doi: 10.1146/annurev.ph.35.030173.000415. [DOI] [PubMed] [Google Scholar]
  23. Leon M. B., Rosing D. R., Bonow R. O., Lipson L. C., Epstein S. E. Clinical efficacy of verapamil alone and combined with propranolol in treating patients with chronic stable angina pectoris. Am J Cardiol. 1981 Jul;48(1):131–139. doi: 10.1016/0002-9149(81)90582-8. [DOI] [PubMed] [Google Scholar]
  24. Livesley B., Catley P. F., Campbell R. C., Oram S. Double-blind evaluation of verapamil, propranolol, and isosorbide dinitrate against a placebo in the treatment of angina pectoris. Br Med J. 1973 Feb 17;1(5850):375–378. doi: 10.1136/bmj.1.5850.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. MELVILLE K. I., BENFEY B. G. CORONARY VASODILATORY AND CARDIAC ADRENERGIC BLOCKING EFFECTS OF IPROVERATRIL. Can J Physiol Pharmacol. 1965 Mar;43:339–342. doi: 10.1139/y65-033. [DOI] [PubMed] [Google Scholar]
  26. Maseri A., Severi S., Nes M. D., L'Abbate A., Chierchia S., Marzilli M., Ballestra A. M., Parodi O., Biagini A., Distante A. "Variant" angina: one aspect of a continuous spectrum of vasospastic myocardial ischemia. Pathogenetic mechanisms, estimated incidence and clinical and coronary arteriographic findings in 138 patients. Am J Cardiol. 1978 Dec;42(6):1019–1035. doi: 10.1016/0002-9149(78)90691-4. [DOI] [PubMed] [Google Scholar]
  27. Matsumoto S., Ito T., Sada T., Takahashi M., Su K. M., Ueda A., Okabe F., Sato M., Sekine I., Ito Y. Hemodynamic effects of nifedipine in congestive heart failure. Am J Cardiol. 1980 Sep;46(3):476–480. doi: 10.1016/0002-9149(80)90018-1. [DOI] [PubMed] [Google Scholar]
  28. Moses J. W., Wertheimer J. H., Bodenheimer M. M., Banka V. S., Feldman M., Helfant R. H. Efficacy of nifedipine in rest angina refractory to propranolol and nitrates in patients with obstructive coronary artery disease. Ann Intern Med. 1981 Apr;94(4 Pt 1):425–429. doi: 10.7326/0003-4819-94-4-425. [DOI] [PubMed] [Google Scholar]
  29. Mueller H. S., Chahine R. A. Interim report of multicenter double-blind, placebo-controlled studies of nifedipine in chronic stable angina. Am J Med. 1981 Oct;71(4):645–657. doi: 10.1016/0002-9343(81)90229-1. [DOI] [PubMed] [Google Scholar]
  30. Nagao T., Matlib M. A., Franklin D., Millard R. W., Schwartz A. Effects of diltiazem, a calcium antagonist, on regional myocardial function and mitochondria after brief coronary occlusion. J Mol Cell Cardiol. 1980 Jan;12(1):29–43. doi: 10.1016/0022-2828(80)90109-1. [DOI] [PubMed] [Google Scholar]
  31. Nayler W. G., Ferrari R., Williams A. Protective effect of pretreatment with verapamil, nifedipine and propranolol on mitochondrial function in the ischemic and reperfused myocardium. Am J Cardiol. 1980 Aug;46(2):242–248. doi: 10.1016/0002-9149(80)90064-8. [DOI] [PubMed] [Google Scholar]
  32. Olivari M. T., Bartorelli C., Polese A., Fiorentini C., Moruzzi P., Guazzi M. D. Treatment of hypertension with nifedipine, a calcium antagonistic agent. Circulation. 1979 May;59(5):1056–1062. doi: 10.1161/01.cir.59.5.1056. [DOI] [PubMed] [Google Scholar]
  33. Pappano A. J. Calcium-dependent action potentials produced by catecholamines in guinea pig atrial muscle fibers depolarized by potassium. Circ Res. 1970 Sep;27(3):379–390. doi: 10.1161/01.res.27.3.379. [DOI] [PubMed] [Google Scholar]
  34. Raabe D. S., Jr Treatment of variant angina pectoris with perhexilene maleate. Chest. 1979 Feb;75(2):152–156. doi: 10.1378/chest.75.2.152. [DOI] [PubMed] [Google Scholar]
  35. Reuter H. Properties of two inward membrane currents in the heart. Annu Rev Physiol. 1979;41:413–424. doi: 10.1146/annurev.ph.41.030179.002213. [DOI] [PubMed] [Google Scholar]
  36. Rosenthal S. J., Ginsburg R., Lamb I. H., Baim D. S., Schroeder J. S. Efficacy of diltiazem for control of symptoms of coronary arterial spasm. Am J Cardiol. 1980 Dec 1;46(6):1027–1032. doi: 10.1016/0002-9149(80)90362-8. [DOI] [PubMed] [Google Scholar]
  37. Rosing D. R., Kent K. M., Borer J. S., Seides S. F., Maron B. J., Epstein S. E. Verapamil therapy: a new approach to the pharmacologic treatment of hypertrophic cardiomyopathy. I. Hemodynamic effects. Circulation. 1979 Dec;60(6):1201–1207. doi: 10.1161/01.cir.60.6.1201. [DOI] [PubMed] [Google Scholar]
  38. Rosing D. R., Kent K. M., Maron B. J., Epstein S. E. Verapamil therapy: a new approach to the pharmacologic treatment of hypertrophic cardiomyopathy. II. Effects on exercise capacity and symptomatic status. Circulation. 1979 Dec;60(6):1208–1213. doi: 10.1161/01.cir.60.6.1208. [DOI] [PubMed] [Google Scholar]
  39. Schamroth L., Krikler D. M., Garrett C. Immediate effects of intravenous verapamil in cardiac arrhythmias. Br Med J. 1972 Mar 11;1(5801):660–662. doi: 10.1136/bmj.1.5801.660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schneider J. A., Sperelakis N. Slow Ca2+ and Na+ responses induced by isoproterenol and methylxanthines in isolated perfused guinea pig hearts exposed to elevated K+. J Mol Cell Cardiol. 1975 Apr;7(4):249–273. doi: 10.1016/0022-2828(75)90084-x. [DOI] [PubMed] [Google Scholar]
  41. Singh B. N., Collett J. T., Chew C. Y. New perspectives in the pharmacologic therapy of cardiac arrhythmias. Prog Cardiovasc Dis. 1980 Jan-Feb;22(4):243–301. doi: 10.1016/0033-0620(80)90011-0. [DOI] [PubMed] [Google Scholar]
  42. Singh B. N., Ellrodt G., Peter C. T. Verapamil: a review of its pharmacological properties and therapeutic use. Drugs. 1978 Mar;15(3):169–197. doi: 10.2165/00003495-197815030-00001. [DOI] [PubMed] [Google Scholar]
  43. Singh B. N., Roche A. H. Effects of intravenous verapamil on hemodynamics in patients with heart disease. Am Heart J. 1977 Nov;94(5):593–599. doi: 10.1016/s0002-8703(77)80128-2. [DOI] [PubMed] [Google Scholar]
  44. Spurrell R. A., Krikler D. M., Sowton E. Effects of verapamil on electrophysiological properties of anomalous atrioventricular connexion in Wolff-Parkinson-White syndrome. Br Heart J. 1974 Mar;36(3):256–264. doi: 10.1136/hrt.36.3.256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Stone P. H., Antman E. M., Muller J. E., Braunwald E. Calcium channel blocking agents in the treatment of cardiovascular disorders. Part II: Hemodynamic effects and clinical applications. Ann Intern Med. 1980 Dec;93(6):886–904. doi: 10.7326/0003-4819-93-6-886. [DOI] [PubMed] [Google Scholar]
  46. Théroux P., Waters D. D., Affaki G. S., Crittin J., Bonan R., Mizgala H. F. Provocative testing with ergonovine to evaluate the efficacy of treatment with calcium antagonists in variant angina. Circulation. 1979 Sep;60(3):504–510. doi: 10.1161/01.cir.60.3.504. [DOI] [PubMed] [Google Scholar]
  47. Waters D. D., Théroux P., Szlachcic J., Dauwe F. Provocative testing with ergonovine to assess the efficacy of treatment with nifedipine, diltiazem and verapamil in variant angina. Am J Cardiol. 1981 Jul;48(1):123–130. doi: 10.1016/0002-9149(81)90581-6. [DOI] [PubMed] [Google Scholar]
  48. Waxman H. L., Myerburg R. J., Appel R., Sung R. J. Verapamil for control of ventricular rate in paroxysmal supraventricular tachycardia and atrial fibrillation or flutter: a double-blind randomized cross-over study. Ann Intern Med. 1981 Jan;94(1):1–6. doi: 10.7326/0003-4819-94-1-1. [DOI] [PubMed] [Google Scholar]
  49. Wit A. L., Cranefield P. F. Effect of verapamil on the sinoatrial and atrioventricular nodes of the rabbit and the mechanism by which it arrests reentrant atrioventricular nodal tachycardia. Circ Res. 1974 Sep;35(3):413–425. doi: 10.1161/01.res.35.3.413. [DOI] [PubMed] [Google Scholar]
  50. Zipes D. P., Besch H. R., Jr, Watanabe A. M. Role of the slow current in cardiac electrophysiology. Circulation. 1975 May;51(5):761–766. doi: 10.1161/01.cir.51.5.761. [DOI] [PubMed] [Google Scholar]

Articles from Western Journal of Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES