Side Effects and Contraindications Drug Interactions and Combinations

  • Lionel H. Opie
  • William A. Coetzee


With the correct selection of drug and patient, the calcium antagonists as a group can be remarkably effective at relatively low cost of serious side effects. Almost all side effects are dose related. Minor side effects include those caused by vasodilation (flushing and headaches), constipation (verapamil), and ankle edema. Serious side effects are rare and result from improper use of these agents, as when intravenous verapamil (or diltiazem) is given to patients with sinus or atrioventricular nodal depression from drugs or disease, or nifedipine to patients with aortic stenosis. The potential of a marked negative inotropic effect is usually offset by afterload reduction, especially in the case of nifedipine which actually has the most marked negative inotropic effect. Yet caution is required when even calcium antagonists, especially verapamil, are given to patients with myocardial failure unless caused by hypertensive heart disease. Drug interactions of calcium antagonists occur with other cardiovascular agents such as α-adrenergic blockers, β-adrenergic blockers, digox in, quinidine, and disopyramide. The most marked interaction with digoxin is that with verapamil, which may raise digoxin levels by over 50%. Combination therapy of calcium antagonists with β-blockers is increasingly common, and is probably safest in the case of dihydropyridines. Other combinations being explored are those with angiotensin-converting enzyme inhibitors and diuretics.


Angina Pectoris Calcium Antagonist Aortic Stenosis Calcium Channel Antagonist Isosorbide Dinitrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gustafsson D. Microvascular mechanisms involved in calcium antagonist edema formation. J Cardiovasc Pharmacol 1987; 10(Suppl 1):S121–S131.PubMedCrossRefGoogle Scholar
  2. 2.
    Subramanian VB. Calcium Antagonists in Chronic Stable Angina Pectoris. Amsterdam: Excerpta Medica, 1983; 97–116, 152–156, 217–229.Google Scholar
  3. 3.
    Lewis JG. Adverse reactions to calcium antagonists. Drugs 1983; 25:196–222.PubMedCrossRefGoogle Scholar
  4. 4.
    Pepine CJ, Feldman RL, Hill JA, et al. Clinical outcome after treatment of rest angina with calcium blockers: Comparative experience during the initial year of therapy with diltiazem, nifedipine, and verapamil. Am Heart J 1983; 106:1341–1347.PubMedCrossRefGoogle Scholar
  5. 5.
    Dawson JR, Whitaker NHG, Sutton GC. Calcium antagonists in chronic stable angina. Comparison of verapamil and nifedipine. Br Heart J 1981; 46:508–512.PubMedCrossRefGoogle Scholar
  6. 6.
    Midtbo K, Hals O, van der Meer J. Verpamil compared with nifedipine in the treatment of essential hypertension. J Cardiouasc Pharmacol 1982; 4(Suppl 3):363–368.Google Scholar
  7. 7.
    Sacks H, Kennelly BM. Verapamil in cardiac arrhythmias (letter). Br Med J 1972; 2:716.PubMedCrossRefGoogle Scholar
  8. 8.
    Fleckenstein A. Specific inhibitors and promoters of calcium action in the excitation-contraction coupling of heart muscle and their role in the prevention or production of myocardial lesions. In: Harris P, Opie LH, eds. Calcium and the Heart. London: Academic Press, 1971; 135–188.Google Scholar
  9. 9.
    Opie LH, White DA. Adverse interaction between nifedipine and beta-blockade. Br Med J 1980; 281:1462–1464.PubMedCrossRefGoogle Scholar
  10. 10.
    Hugenholtz P, Verdouw PD, de Jong JW, et al. Nifedipine for angina and acute myocardial ischemia. In: Opie LH, ed. Calcium Antagonists and Cardiovascular Disease. New York: Raven Press, 1984; 237–255.Google Scholar
  11. 11.
    Opie LH. Drugs and the Heart. London: Lancet, 1980; 27–38.Google Scholar
  12. 12.
    Opie LH, Singh BN. Calcium channel antagonists (slow channel blockers). In: Opie LH, ed. Drugs for the Heart Second Expanded Edition. Orlando, Florida: Grune amp; Stratton, 1987; 34–53Google Scholar
  13. 13.
    Norris RJ, Brooks SG. Pharmacokinetics of a sustained release formulation of verapamil in young and elderly adults. In: Raftery EB, ed. Verapamil SR. Once-daily Calcium Blockade in Angina and Hypertension. Lang-horne: ADIS Press International, 1987; 38–46.Google Scholar
  14. 14.
    Brodsky SJ, Cutler SS, Weiner DA, et al. Hepatotoxicity due to treatment with verapamil. Ann Intern Med 1981; 94:490–491.PubMedGoogle Scholar
  15. 15.
    Terry RW. Nifedipine therapy in angina pectoris: Evaluation of safety and side effects. Am Heart J 1982; 104:681–689.PubMedCrossRefGoogle Scholar
  16. 16.
    Leisten L, Kuhlmann J, Ebner F. Side effects and pharmacodynamic interactions. In: Krebs R, ed. Treatment of Cardiovascular Diseases by Adalat ® (Nifedipine). Stuttgart-New York: Schattauer, 1986; 270–314.Google Scholar
  17. 17.
    Prida XE, Gelman JS, Feldman RL, et al. Comparison of diltiazem and nifedipine alone and in combination in patients with coronary artery spasm. J Am Coll Cardiol 1987; 9:412–419.PubMedCrossRefGoogle Scholar
  18. 18.
    MacDonald JB. Muscle cramps during treatment with nifedipine (Letter). Br Med J 1982; 285:1744.CrossRefGoogle Scholar
  19. 19.
    Jee LD, Opie LH. Nifedipine for hypertension and angina pectoris: Interactions during combination therapy. In: Opie LH, ed. Calcium Antagonists and Cardiovascular Disease. New York: Raven Press, 1984; 339–346.Google Scholar
  20. 20.
    Jariwalla AG, Anderson EG. Production of ischaemic cardiac pain by nifedipine. Br Med J 1978; 1:1181–1182.PubMedCrossRefGoogle Scholar
  21. 21.
    Sia STB, MacDonald PS, Triester B, et al. Aggravation of myocardial ischaemia by nifedipine. Med J Aust 1985; 142:48–50.PubMedGoogle Scholar
  22. 22.
    Bertel O, Conen D, Radu EW, et al. Nifedipine in hypertensive emergencies. Br Med J 1983; 286:19–21.CrossRefGoogle Scholar
  23. 23.
    Opie LH. Fluid retention with nifedipine in antihypertensive therapy. Lancet 1986; ii:1456.CrossRefGoogle Scholar
  24. 24.
    Marone C, Luisoli S, Bornio F, et al. Body sodium-blood volume state, aldosterone, and cardiovascular responsiveness after calcium entry blockade with nifedipine. Kidney Int 1985; 28:658–665.PubMedCrossRefGoogle Scholar
  25. 25.
    Guazzi MD, De Cesare N, Galli C, et al. Calcium-channel blockade with nifedipine and angiotensin converting-enzyme inhibition with Captopril in the therapy of patients with severe primary hypertension. Hypertension 1984; 70:279–284.Google Scholar
  26. 26.
    Gillmer DJ, Kark P: Pulmonary oedema precipitated by nifedipine. Br Med J 1980; 280:1420–1421.PubMedCrossRefGoogle Scholar
  27. 27.
    Diamond JR, Cheung JY, Fang LST. Nifedipine-induced renal dysfunction. Alterations in renal hemodynamics. Am J Med 1984; 77:905–909.PubMedCrossRefGoogle Scholar
  28. 28.
    Krebs R. Adverse reactions with calcium antagonists. Hypertension 1983; 5(Suppl II):II–125–n–129.Google Scholar
  29. 29.
    Bhatnager SK, Amin MMA, Al-Yusuf AR. Diabetogenic effects of nifedipine. Br Med J 1984; 289:19.CrossRefGoogle Scholar
  30. 30.
    Murphy MB, Scriven AJI, Dollery CT. Role of nifedipine in treatment of hypertension. Br Med J 1983; 287:257–259.CrossRefGoogle Scholar
  31. 31.
    Myers MG, Leenen FHH, Burns R, et al. Nifedipine tablet vs hydralazine in patients with persisting hypertension who receive combined diuretic and beta-blocker therapy. Clin Pharmacol Ther 1986; 39:409–413.PubMedCrossRefGoogle Scholar
  32. 32.
    Sowers JR, Mohanty PK. Comparison of calcium-entry blockers and diuretics in the treatment of hypertensive patients. Circulation 75(Suppl V):V170–V173.Google Scholar
  33. 33.
    Hossack KF, Pool PE, Steele P, et al. Efficacy of diltiazem in angina of effort: A multicenter trial. Am J Cardiol 1982; 49:567–572.PubMedCrossRefGoogle Scholar
  34. 34.
    Lindenberg BS, Weiner DA, McCabe CH, et al. Efficacy and safety of incremental doses of diltiazem for the treatment of stable angina pectoris. J Am Coll Cardiol 1983; 2:1129–1133.PubMedCrossRefGoogle Scholar
  35. 35.
    Moser M. Calcium entry blockers for systematic hypertension. Am J Cardiol 1987; 59:15A–121A.CrossRefGoogle Scholar
  36. 36.
    Petru MA, Crawford MH, Sorenson SG, et al. Short-and long-term efficacy of high-dose oral diltiazem for angina due to coronary artery disease: A placebo-controlled, randomized, double-blind crossover study. Circulation 1983; 68:139–147.PubMedCrossRefGoogle Scholar
  37. 37.
    Pool PE, Massie BM, Venkararaman K, et al. Diltiazem as monotherapy for systemic hypertension: A multicenter, randomized, placebo-controlled trial. Am J Cardiol 1986; 57:212–217.PubMedCrossRefGoogle Scholar
  38. 38.
    Roth A, Harrison E, Mitani G, et al. Efficacy and safety of medium-and high-dose diltiazem alone and in combination with digoxin for control of heart rate at rest and during exercise in patients with chronic atrial fibrillation. Circulation 1986; 73:316–324.PubMedCrossRefGoogle Scholar
  39. 39.
    Steinberg JS, Katz RJ, Bren GB, et al. Efficacy of oral diltiazem to control ventricular response in chronic atrial fibrillation at rest and during exercise. J Am Coll Cardiol 1987; 9:405–411.PubMedCrossRefGoogle Scholar
  40. 40.
    Ishikawa T, Imamura T, Koiwaya Y, et al. Atrioventricular dissociation and sinus arrest induced by oral diltiazem. New Engl J Med 1983; 309:1124–1125.PubMedCrossRefGoogle Scholar
  41. 41.
    Hung J, Lamb IH, Connolly SJ, et al. The effect of diltiazem and propranolol, alone and in combination, on exercise performance and left ventricular function in patients with stable effort angina: A double-blind, randomized, and placebo controlled study. Circulation 1983; 68:560–567.PubMedCrossRefGoogle Scholar
  42. 42.
    Strauss WE, Egan T, McIntyre KM, et al. Combination therapy with diltiazem and propranolol: Precipitation of congestive heart failure. Clin Cardiol 1985; 8:363–366.PubMedCrossRefGoogle Scholar
  43. 43.
    CMS Update. Annual review of yellow cards-1985. Br Med J 1986; 293:688.CrossRefGoogle Scholar
  44. 44.
    Bardet J, Baudet M, Rigaud M, et al. Diltiazem, a new calcium antagonist, versus propranolol in treatment of spontaneous angina pectoris (abstr). Am J Cardiol 1979; 43:416.Google Scholar
  45. 45.
    Krikler DM, Curry VL. Torsade de pointes, an atypical ventricular tachycardia. Br Heart J 1976; 38:117–120.PubMedCrossRefGoogle Scholar
  46. 46.
    Hanley SP, Hampton JR: Ventricular arrhythmias associated with lidoflazine: side-effects observed in a randomized trial. Eur Heart J 1983; 4:889–893.PubMedGoogle Scholar
  47. 47.
    Ferlinz J, Citron PD. Hemodynamics and myocardial performance characteristics after verapamil use in congestive heart failure. Am J Cardiol 1983; 51:1339–1345.PubMedCrossRefGoogle Scholar
  48. 48.
    Piepho RW, Culbertson VL, Rhodes RS. Drug interactions with the calcium-entry blockers. Circulation 1987: 75(Suppl V):V–181–V–194.Google Scholar
  49. 49.
    Jee LD, Opie LH. Acute hypotensive response to nifedipine added to prazosin in treatment of hypertension. Br Med J 1983; 287:1514–1516.CrossRefGoogle Scholar
  50. 50.
    Sluiter HE, Huysmans F Th M, Thien Th A, et al. The influence of alpha1-adrenergic blockade on the acute antihypertensive effect of nifedipine. Eur J Clin Pharmacol 1985; 29:263–267.PubMedCrossRefGoogle Scholar
  51. 51.
    Elliott HL, Pasanisi F, Meredith PA, et al. Acute hypotensive response to nifedipine added to prazosin. Br Med J 1984; 288:238.CrossRefGoogle Scholar
  52. 52.
    Pasanisi F, Elliot HL, Meredith PA, et al. Combined alpha-adrenoceptor antagonism and calcium channel blockade in normal subjects. Clin Pharmacol Ther 1984; 36:716–723.PubMedCrossRefGoogle Scholar
  53. 53.
    Menasche S, Elkik F, Cocco G, et al. Synergistic antihypertensive effect of diltiazem combined with the alpha-adrenoceptor blocker alfuzosine (abstr). Presentation to NY Acad Sci, Feb 1987.Google Scholar
  54. 54.
    Urthaler F, James TN. Experimental studies on the pathogenesis of asystole after verapamil in the dog. Am J Cardiol 1979; 44:651–656.PubMedCrossRefGoogle Scholar
  55. 55.
    Kieval J, Kirstein EB, Kessler KM, et al. The effects of intravenous verapamil on hemodynamic status of patients with coronary artery disease receiving propranolol. Circulation 1982; 65:653–659.PubMedCrossRefGoogle Scholar
  56. 56.
    Packer M, Meller J, Medina N, et al. Hemodynamic consequences of combined beta-adrenergic and slow calcium channel blockade in man. Circulation 1982; 65:660–668.PubMedCrossRefGoogle Scholar
  57. 57.
    Johnston DL, Lesoway R, Humen DP, et al. Clinical and hemodynamic evaluation of propranolol in combination with verapamil, nifedipine and diltiazem in extertional angina pectoris: A placebo-controlled, double-blind, randomized, crossover study. Am J Cardiol 1985; 55:680–687.PubMedCrossRefGoogle Scholar
  58. 58.
    Winniford MD, Fulton KL, Corbett JR. et al. Propranololverapamil versus propranolol-nifedipine in severe angina pectoris of effort: A randomized, double-blind crossover study. Am J Cardiol 1985; 55:281–285.PubMedCrossRefGoogle Scholar
  59. 59.
    McLean AJ, Knight R, Harrison PM, et al. Clearance based oral drug interaction between verapamil and metoprolol and comparison with atenolol. Am J Cardiol 1985; 55:1628–1629.PubMedCrossRefGoogle Scholar
  60. 60.
    Pfisterer M, Muller-Brand J, Burkart F. Combined acebutolol/nifedipine therapy in patients with chronic coronary artery disease: Additional improvement of ischemia-induced left ventricular dysfunction. Am J Cardiol 1982; 49:1259–1266.PubMedCrossRefGoogle Scholar
  61. 61.
    Millard RW, Lathrop DA, Grupp G, et al. Differential cardiovascular effects of calcium channel blocking agents: Potential mechanisms. Am J Cardiol 1982; 49:449–506.CrossRefGoogle Scholar
  62. 62.
    Warltier DC, Zyvolski MG, Gross GJ, et al. Comparative actions of dihydropyridine slow channel calcium blocking agents in conscious dogs: systemic and coronary hemodynamics with and without combined beta adrenergic blockade. J Pharmacol Exp Ther 1984; 230:367–375.PubMedGoogle Scholar
  63. 63.
    Lynch P, Dargie H, Krikler S, et al. Objective assessment of antianginal and their combination. Br Med J 1980; 281:184–187.PubMedCrossRefGoogle Scholar
  64. 64.
    Opie LH, Jee L, White D. Antihypertensive effects of nifedipine combined with cardioselective beta-adrenergic receptor antagonism by atenolol. Am Heart J 1982; 104:606–612.PubMedCrossRefGoogle Scholar
  65. 65.
    Brooks N, Cattell M, Pidgeon J, et al. Unpredictable response to nifedipine in severe cardiac failure (letter). Br Med J 1980; 281:1324.PubMedCrossRefGoogle Scholar
  66. 66.
    Hamann SR, Kaltenborn KE, McAllister RG. Nifedipine-propranolol interaction: Dependence of cardiovascular effects on plasma drug concentrations. J Cardiovasc Pharmacol 1987; 10:182–189.PubMedCrossRefGoogle Scholar
  67. 67.
    Kleinbloesem CH, van Brummelen P, Sandberg THW, et al. Kinetic and haemodynamic interactions between nifedipine and propranolol in healthy subjects utilizing controlled rates of drug input. In: Kleinbloesem CH, ed. Nifedipine: Clinical Pharmacokinetics and Haemodynamic Effects. ’s-Gravenhage: Drukkerij JH Pasmans BV, 1985; 151–165.Google Scholar
  68. 68.
    Rosenkranz B, Ledermann H, Frolich JC. Interaction between nifedipine atenolol: pharmacokinetics and pharmacodynamics in normotensive volunteers. J Cardiovasc Pharmacol 1986; 8:943–949.PubMedCrossRefGoogle Scholar
  69. 69.
    Chaffman M, Brogden RN: Diltiazem: A review of its pharmacological properties and therapeutic efficacy. Drugs 1985; 29:387–454.PubMedCrossRefGoogle Scholar
  70. 70.
    Tilmant PY, Lablanche JM, Thieuleux FA, et al. Detrimental effect of propranolol in patients with coronary arterial spasm countered by combination with diltiazem. Am J Cardiol 1983; 52:230–233.PubMedCrossRefGoogle Scholar
  71. 71.
    Rocha P, Zannier D, Baron B, et al. Acute hemodynamic effects of intravenous nicardipine in patients treated chronically with propranolol for coronary artery disease. Am J Cardiol 1987; 59:775–781.PubMedCrossRefGoogle Scholar
  72. 72.
    Culling W, Ruttley MSM, Sheridan DJ. Acute haemodynamic effects of delodipine during beta-blockade in patients with coronary artery disease. Br Heart J 1984; 52:431–434.PubMedCrossRefGoogle Scholar
  73. 73.
    Duncker DJ, Hartog JM, Hugenholtz PG, et al. The effects of nisoldipine (Bay K 5552) on cardiovascular performance and regional blood flow in pentobarbital — anesthetized pigs with or without β-adrenoceptor blockade. Br J Pharmacol 1986; 88:9–18.PubMedGoogle Scholar
  74. 74.
    Kimura E, Kishida H: Treatment of variant angina with drugs: A survey of 11 cardiology institutes in Japan. Circulation 1981; 63:844–848.PubMedCrossRefGoogle Scholar
  75. 75.
    Toyosaki N, Natsume T, Katsuki T, et al. Synergetic effects of nifedipine and diltiazem in effort angina pectoris (abstr). Circulation 1987; 76(Suppl IV):IV-92.Google Scholar
  76. 76.
    Lessem J, Bellinetto A. Interaction between digoxin and calcium antagonist (abstr). Am J Cardiol 1982; 49:1025.CrossRefGoogle Scholar
  77. 77.
    Pedersen KE. Digoxin interactions. The influence of quinidine and verapamil on the pharmacokinetics and receptor binding of digitalis glycosides. Acta Med Scand 1985; (Suppl 697): 12–40.Google Scholar
  78. 78.
    Schwartz JB, Raizner A, Akers S. The effect of nifedipine on serum digoxin concentrations in patients. Am Heart J 1984; 107:669–673.PubMedCrossRefGoogle Scholar
  79. 79.
    Elkayam U, Parikh K, Torkan B, et al. Effect of diltiazem on renal clearance and serum concentration of digoxin in patients with cardiac disease. Am J Cardiol 1985; 55:1393–1395.PubMedCrossRefGoogle Scholar
  80. 80.
    Oyama Y, Fujii S, Kanda K, et al. Digoxin-diltiazem interaction. Am J Cardiol 1984; 53: 1480–1481.PubMedCrossRefGoogle Scholar
  81. 81.
    Kleinbloesem CH, van Brummelen P, Hillers J, et al. Interaction between digoxin and nifedipine at steady-state in patients with atrial fibrillation. In: Kleinbloesem CH, ed. Nifedipine: Clinical Pharmacokinetics and Haemodynamic Effects. ’s-Gravenhage: Drukkerij JH Pasms BV, 1985; 167–173.Google Scholar
  82. 82.
    Kirch W. Dihydropyridine derivatives, influence on digoxin disposition and haemodynamics (abstr). Presentation to NY Acad Sci, Feb 1987.Google Scholar
  83. 83.
    Kirch W, Hutt HJ, Heidemann H, et al. Drug interactions with nitrendipine. J Cardiovasc Pharmacol 1984; 6(Suppl 7):S982–S985.PubMedGoogle Scholar
  84. 84.
    Cantelli I, Bracchetti D. Combined use of digoxin and nifedipine in the treatment of congestive heart failure. Pract Cardiol 1985; 11:75–87.Google Scholar
  85. 85.
    Maisel AS, Motulsky HJ, Insel PA. Hypotension after quinidine plus verapamil. New Engl J Med 1985; 312:167–171.PubMedCrossRefGoogle Scholar
  86. 86.
    Lee JT, Davy J-M, Kates RE. Evaluation of combined administration of verapamil and disopyramide in dogs. J Cardiovasc Pharmacol 1985; 7:501–507.PubMedCrossRefGoogle Scholar
  87. 87.
    MacPhee GJA, McInnes GT, Thompson GG, et al. Verapamil potentiates carbamazepine neurotoxicity: A clinically important inhibitory interaction. Lancet 1986; i:700–703.CrossRefGoogle Scholar
  88. 88.
    Bassan MM, Weiler-Ravell D, Shalev O. Comparison of the antianginal effectiveness of nifedipine, verapamil and isosorbide dinitrate in patients receiving propranolol: A double-blind study. Circulation 1983; 68:568–575.PubMedCrossRefGoogle Scholar
  89. 89.
    Tolins M, Weir EK, Chesler E, et al. “Maximal” drug therapy is not necessarily optimal in chronic angina pectoris. J Am Coll Cardiol 1984; 3:1051–1057.PubMedCrossRefGoogle Scholar
  90. 90.
    White HD, Polak JF, Wynne J, et al. Addition of nifedipine to maximal nitrate and beta-adrenoceptor blocker therapy in coronary artery disease. Am J Cardiol 1985; 55:1303–1307.PubMedCrossRefGoogle Scholar
  91. 91.
    Singer DRJ, Markandu ND, Shore AC, et al. Captopril and nifedipine in combination for moderate to severe essential hypertension. Hypertension 1987; 9:629–633.PubMedGoogle Scholar
  92. 92.
    Muller FB, Bolli P, Linder L, et al. Calcium antagonists and the second drug for hypertensive therapy. Am J Med 1986; 81(Suppl 6A):25–29.PubMedCrossRefGoogle Scholar
  93. 93.
    MacGregor GA: Hypertension. In: Krebs R, ed. Treatment of Cardiovascular Diseases by Adalat ® (Nifedipine). Stuttgart: Schattauer, 1986; 231–258.Google Scholar
  94. 94.
    Daniels AR, Opie LH. Atenolol plus nifedipine for mild to moderate systemic hypertension after fixed doses of either agent alone. Am J Cardiol 1986; 57:965–970.PubMedCrossRefGoogle Scholar
  95. 95.
    Smith SR, Kendall MJ, Lobo J, et al. Ranitidine and Cimetidine: Drug interactions with single dose and steady-state nifedipine administration. Br J Clin Pharmacol 1987; 23:311–315.PubMedGoogle Scholar
  96. 96.
    Kirch W, Janisch HD, Heidmann H, et al. Effect of Cimetidine and ranitidine on the pharmacokinetics and the antihypertensive action of nifedipine. Dtsch Med Wochenschr 1983; 108:1757–1761.PubMedCrossRefGoogle Scholar
  97. 97.
    Lahiri A, Dasgupta P, Rodrigues EA, et al. Acute drug withdrawal in patients with stable angina on long-term treatment with verapamil. In: Raftery EB, ed. Verapamil SR. Langhorne: ADIS Press International, 1987; 18–29.Google Scholar
  98. 98.
    Raftos J, Verapamil in the long-term treatment of angina pectoris. Med J Aust 1980; 2:78–80.PubMedGoogle Scholar
  99. 99.
    Stone PH. Calcium antagonists for Prinzmetal’s variant angina, unstable angina and silent myocardial ischemia. Therapeutic tool and probe for identification of pathophysiologic mechanisms. Am J Cardiol 1983; 59:101B–115B.CrossRefGoogle Scholar
  100. 100.
    Gottlieb SO, Ouyang P, Achuff SC, et al. Acute nifedipine withdrawal:Consequences of preoperative and late cessation of therapy in patients with prior unstable angina. J Am Coll Cardiol 1984; 4:383–388.CrossRefGoogle Scholar
  101. 101.
    Sorkin EM, Clissold SP, Brogden RN. Nifedipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in ischemic heart disease, hypertension and related cardiovascular disorders. Drugs 1985; 30:182–274.PubMedCrossRefGoogle Scholar
  102. 102.
    Frishman W, Zawada ET, Smith K, et al. Comparison of hydrochlorothiazide and sustained-release diltiazem for mild to moderate systemic hypertension. Am J Cardiol 1987; 59:615–623.PubMedCrossRefGoogle Scholar
  103. 103.
    Schroeder JS, Walker SD, Skalland ML, et al. Absence of rebound from diltiazem therapy in Prinzmetal’s variant angina. J Am Coll Cardiol 1985; 6:174–178.PubMedCrossRefGoogle Scholar
  104. 104.
    Daniels AR, Opie LH. Monotherapy with the calcium channel antagonist nisoldipine for systemic hypertension and comparison with diuretic drugs. Am J Cardiol 1987; 60:703–707.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Lionel H. Opie
    • 1
    • 2
  • William A. Coetzee
    • 3
  1. 1.University of Cape TownCape TownSouth Africa
  2. 2.Division of CardiologyStanford University Medical CenterStanfordUSA
  3. 3.Heart Research UnitUniversity of Cape TownSouth Africa

Personalised recommendations