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Calciumantagonisten in der Therapie der Hypertonie

Calcium antagonists in the treatment of hypertension

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Summary

Calcium antagonists (nifedipine, verapamil, diltiazem) are potent vascular smooth muscle relaxants. Experimental and clinical investigations provide growing evidence that they are effective in acute and (sub)chronic therapy of arterial hypertension by lowering peripheral vascular resistance and improvement of altered hemodynamics — independent from pathogenesis of hypertension. Due to its prompt and profound hypotensive action, sublingual or oral nifedipine has been used successfully in hypertensive crises. The hypotensive effect usually correlates closely with the severity of hypertension and is nearly absent in normotensive controls. Since the blood pressure drop may occasionally result in absolute or relative hypotension, the initial dose should be as low as possible. The activation of the adrenergic and renin angiotensin systems seen after nifedipine administration is less pronounced after chronic administration of the drug and is nearly absent after verapamil and diltiazem. Plasma aldosterone concentrations remain constant or are slightly decreased.

In contrast to classic vasodilators, the long-term administration of calcium antagonists usually does not result in tachycardia (nifedipine), but slight sinus bradycardia (verapamil, diltiazem). Peripheral edema may occasionally occur after nifedipine. A tolerance has been observed during long-term treatment of hypertension.

Combining these drugs (verapamil, diltiazem) with betablockers is not recommended due to the negative inotropic and bathmotropic effects. Simultaneous administration of nifedipine and beta-blockers enhances the hypotensive action, but favours the development of peripheral edema and in rare cases (especially in severe coronary heart disease) results in a dramatic drop in blood pressure and/or congestive heart failure.

Further clinical evaluation and long-term trials of calcium antagonists as antihypertensive agents will be needed before definite conclusions can be drawn.

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Literatur

  1. Aoki K, Yoshida T, Kato S, Tazumi K, Sato I, Takikawa K, Hotta K (1976) Hypotensive action and increased plasma renin activity by Ca2+-antagonist (nifedipine) in hypertensive patients. Jap Heart J 17:479–484

    Google Scholar 

  2. Aoki K, Kondo S, Mochizuki A, Yoshida T, Kato S, Kato K, Takikawa K (1978) Antihypertensive effect of cardiovascular Ca2+-antagonist in hypertensive patients in the abscnce and presence of beta-adrenergic blockade. Am Heart J 96:218–226

    Google Scholar 

  3. Bartorelli C (1978) Haemodynamic effects of a calcium antagonistic agent (nifedipine) in hypertension: therapeutic implications. Clin Sci Mol Med 55 [Suppl. 4]:291s-292s

    Google Scholar 

  4. Beer N, Gallegos I, Cohen A, Klein N, Sonnenblick E, Frishman W (1981) Efficacy of sublingual nifedipine in the acute treatment of systemic hypertension. Chest 97:571–574

    Google Scholar 

  5. Bertel O, Conen D, Radu EW, Müller J, Lang C, Dubach CD (1983) Nifedipine in hypertension emergencies. Br Med J 286:19–21

    Google Scholar 

  6. Blaustein MP (1978) The role of calcium in catecholamine release from adrenergic nerve terminals. In: Paton DE (ed) The release of catecholamines from adrenergic neurons. Pergamon, Oxford New York, pp 39–58

    Google Scholar 

  7. Brittinger WD, Schwarzbeck A, Wittenmeier KW, Twittenhoff WD, Stegara B, Huber W, Ewald RW, v. Henning EE, Fabricius M, Strauch M (1970) Klinisch-experimentelle Untersuchungen über die blutdrucksenkende Wirkung von Verapamil. Dtsch Med Wochenschr 37:1871–1877

    Google Scholar 

  8. Bühler FR, Hulthen L, Bolli P, Kiowski W (1981) Verapamil bewirkt eine potente Vasodilatation — besonders bei älteren und nieder-Renin-Patienten. Abstract 5. Tag der wiss. Sektion der Deutschen Liga zur Bekämpfung des hohen Blutdruckes, München. Therapiewoche 47:7754

    Google Scholar 

  9. Charles ST, Ketelslegers JM, Buysschaert M, Lambert A (1981) Hyperglycaemic effect of nifedipine. Br Med J 283:19

    Google Scholar 

  10. Corea L, Miele N, Bentivoglio M, Boschetti E, Agabiti RE, Muiesan G (1979) Acute and chronic effects of nifedipine on plasma renin activity and plasma adrenaline and noradrenaline in controls and hypertensive patients. Clin Sci 57 [Suppl 5]:115s-117s

    Google Scholar 

  11. DeMarinis L, Barbarino A (1980) Calcium antagonists and hormone release. I. Effects of verapamil on insulin release in normal subjects and patients with islet-cell tumor. Metabolism 29:599–602

    Google Scholar 

  12. Devis G, Somers G, v. Oberghen E, Malaisse WJ (1975) Calcium antagonists and islct function. I Inhibition of insulin release by verapamil. Diabetes 24:547–551

    Google Scholar 

  13. Donnelly T, Harrower ADB (1980) Effect of nifedipine on glucose tolerance and insulin secretion in diabetic and non-diabetic patients. Current Med Res Opinion 6:690–693

    Google Scholar 

  14. Fakunding JL, Catt KJ (1980) Dependence of aldosterone stimulation in adrenal glomerulosa cells on calcium uptake: effects of lanthanum and verapamil. Endocrinology 107:1345–1353

    Google Scholar 

  15. Fleckenstein A, Fleckenstein-Grün G (1981) Calcium-Antagonismus — ein neues Wirkungsprinzip in der Koronartherapie. Münch Med Wochenschr 123 [Suppl 1]:S15-S21

    Google Scholar 

  16. Frey M, Witzleben H, v. Keidel JA, Fleckenstein A (1980) Restriction of Ca-overload of the arterial walls of spontaneously hypertensive rats (SHR) by Ca-antagonists. Naunyn Schmiedebergs Arch Pharmacol 313 [Suppl R]:48

    Google Scholar 

  17. Garthoff B, Kazda S (1981) Calcium antagonist nifedipine normalizes high blood pressure and prevents mortality in salt-loaded DS substrain of Dahl rats. Eur J Pharmacol 74:111–112

    Google Scholar 

  18. Gillmer DJ, Kark P (1980) Pulmonary oedema precipitated by nifedipine. Br Med J 280:1420–1421

    Google Scholar 

  19. Giugliano D, Torella R, Cacciapuoti F, Gentile S, Verza M, Varriocchio M (1980) Impairment of insulin secretion in many by nifedipine. Eur J Clin Pharmacol 18:395–398

    Google Scholar 

  20. Greenwood RH (1982) Hyperglycaemic effect of nifedipine. Br Med J 284:50

    Google Scholar 

  21. Guazzi M, Olivari MT, Polesc A, Fiorentini C, Magrini F, Moruzzi P (1977) Nifedipine, a new antihypertensive with rapid action. Clin Pharm Ther 22:528–532

    Google Scholar 

  22. Guazzi M, Fiorentini C, Olivari MT, Bartorelli A, Necchi G, Polese A (1980) Short- and long-term efficacy of a calcium-antagonistic agent (nifedipine) combined with methyldopa in the treatment of severe hypertension. Circulation 61:913–919

    Google Scholar 

  23. Haas H, Härtfelder B (1962) α-Isopropyl-α-(N-methyl-homoveratryl)-γ-aminopropyl)-3,4-dimethoxyphenyl-acetonitril, eine Substanz mit coronargefäßerweiternden Eigenschaften. Arzneim Forsch (Drug Res) 12:549–558

    Google Scholar 

  24. Heidbreder E, Ziegler A, Heidland A (1983) Diuretics and calcium antagonists: circulatory parameters and plasma catecholamines during mental stress. Eur J Pharmacol (in press)

  25. Heidland A, Klütsch K, Öbek A (1962) Myogenbedingte Vasodilatation bei Nierenischämie. Münch Med Wochenschr 35:1636–1637

    Google Scholar 

  26. Heidland A, Heidbreder E, Hörl WH, Schäfer R (1982) Calcium antagonists in the treatment of hypertension. Contrib Nephrol 33:254–269

    Google Scholar 

  27. Henry PD (1980) Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol 46:1047–1058

    Google Scholar 

  28. Hermansen K, Iversen J (1977) Effect of verapamil on pancreatic glucagon release from the isolated perfused canine pancreas. Scand J Clin Lab Invest 37:139–142

    Google Scholar 

  29. Hiramatsu K, Yamagashi F, Yamada T (1981) Acute effects of calcium antagonist, nifedipine, on blood pressure, pulse rate, renin-angiotensin-aldosterone system in young and old patients with essential hypertension. 8th Scientific Meeting of the Int Soc Hypert, Milan, Abstract 1880

  30. Husted SE, Nielsen HK, Christensen CK, Lederballe-Pederson O (1982) Long-therm therapy of arterial hypertension with nifedipine given alone or in combination with a beta-adrenoceptor blocking agent. Eur J Clin Pharmacol 22:101–103

    Google Scholar 

  31. Ikeda M, Aoki K, Arakawa K (1979) Clinical effect of diltiazem (Herbesser®) on essential hypertension. Comparison with placebo by double-blind method. Med Progress 110:302–318

    Google Scholar 

  32. Ishii H, Itoh K, Nosc T (1980) Different antihypertensive effects of nifedipine in conscious experimental hypertensive and normotensive rats. Eur J Pharmacol 64:21–29

    Google Scholar 

  33. Kinoshita M, Kusukawa R, Shimono Y (1978) Effects of diltiazem hydrochloride on renal hemodynamics and urinary electrolyte excretion. Jap Circul J 42:553–560

    Google Scholar 

  34. Kiowski W, Bertel O, Ritz R, Bühler FR (1982) Antihypertensiver Wirkmodus von Nifedipin bei essentieller Hypertonic. 6. Tagung der Deutschen Liga zur Bekämpfung des hohen Blutdruckes. Abstrakt. Therapiewoche 32:S5736

  35. Kiyomoto A (1979) Antihypertensive effects of diltiazem in rats. In: Bing RJ (ed) New drug therapy with a calcium antagonist. Diltiazem Hakone Symposium 1978. Excerpta Medica, Amsterdam Princeton, pp 112–125

    Google Scholar 

  36. Kochsiek K, Neubauer J (1972) The effect of 4-(2′-nitrophenyl)-2,6-dimethyl-3,5-dicarbomethoxy-1,4-dihydropyridine on myocardial metabolism, haemodynamies, blood gases and general metabolism in man. Arzneim Forsch (Drug Res) 22:358–362

    Google Scholar 

  37. Koch-Weser J (1974) Vasodilator drugs in the treatment of hypertension. Arch Intern Med 133:1017–1027

    Google Scholar 

  38. Klütsch K, Schmidt P, Großwendt J (1972) Der Einfluß von BAY a 1040 auf die Nierenfunktion des Hypertonikers. Arzneim Forsch (Drug Res) 22:377–380

    Google Scholar 

  39. Kusukawa R, Kinoshita M, Shimono Y, Tomonaga G, Hosino T (1977) Haemodynamic effects of a new antianginal drug, diltiazem hydrochloride. Arzneim Forsch (Drug Res) 27:878–887

    Google Scholar 

  40. Kuwajima I, Nagura H, Sakai M, Hada Y, Kamata C, Mifune JI, Miatsushita S (1977) Effect of nifedipine in hypertensive emergency and in severe intractable hypertension. Jap Circul J 41:748–749

    Google Scholar 

  41. Kuwajima I, Ueda K, Kamata C, Matsushita S, Kuramoto K, Murakami M, Hada Y (1978) A study on the effects of nifedipine in hypertensive crises and severe hypertension. Jap Heart J 19:455–467

    Google Scholar 

  42. Laaser CH, Meurer KA, Kaufmann W (1977) Zur klinischen Bewertung der Kombinationsbehandlung von Nifedipin mit verschiedenen Antihypertensiva. Arzneim Forsch (Drug Res) 27:676–681

    Google Scholar 

  43. Lederballe-Pedersen O, Mikkelsen E (1978) Acute and chronic effects of nifedipine in arterial hypertension. Eur J Clin Pharmacol 14:375–381

    Google Scholar 

  44. Lederballe-Pedersen D (1978) Does verapamil have a clinically significant antihypertensive effect? Eur J Clin Pharmacol 13:21–24

    Google Scholar 

  45. Lederballe-Pedersen O, Mikkelsen E, Christensen NJ, Kornerup HJ, Pedersen EB (1979) Effect of nifedipine on plasma renin, aldosterone and catecholamines in arterial hypertension. J Clin Pharmacol 15:235–240

    Google Scholar 

  46. Leinetti G, Sala C, Bianchini C, Terzoli L, Zanchetti A (1980) Antihypertensive and renal effects of orally administered verapamil. Eur J Clin Pharmacol 18:375–382

    Google Scholar 

  47. Levy J, Herchuelz A, Sener A, Malaisse WJ (1975) Inhibition by verapamil of calcium influx in theβ-cell. Diabetes 24 [Suppl 2]:400–403

    Google Scholar 

  48. Lewis GRJ, Morley KD, Maslowski AH, Bones PJ (1979) Verapamil in the management of hypertensive patients. Aust NZJ Med 9:62–64

    Google Scholar 

  49. Lydtin H, Lohmöller G, Lohmöller R, Schmitz H, Walter J (1975) Hemodynamic studies of adalat in healthy volunteers and in patients. In: Lochner W, Braasch W, Kroneberg G (eds): 2nd International Adalat Symposium: New Therapy of Ischemic Heart Disease. Excerpta Medica Berlin pp 112–123

  50. MacGregor GA, Markandu ND, Bayliss J, Brown MJ, Roulston JE (1981) Evidence from studies with nifedipine of a functional abnormality of smooth muscle in essential hypertension. 8th Scientific Meeting of the Int Soc Hypert, MIlan. Abstract 264

  51. McCrorey HL, Berl T, de Torrente A, Schrier RW (1979) Effect of calcium (Ca) transport inhibitors on renal hemodynamics and electrolyte excretion in the dog. Kidney Int 16:857

    Google Scholar 

  52. Magometschnigg P, Ramcis H, Scrtl K (1981) 20 mg nifedipine per os: blood pressure response in normals, in moderate, severe and in emergency hypertension. 8th Scientific Meeting of the Int Soc Hypert, Milan. Abstract 266

  53. Maier H, Antonczyk G, Schindler JG, Heidland A (1980) Alterations in ionized and total calcium concentrations in parotid sliva in patients with essential hypertension. Mineral Electrolyt Metab 3:109–111

    Google Scholar 

  54. Malaisse WJ, Boschero AC (1977) Calcium antagonists and islet function. XI. Effect of nifedipine. Hormone Res 8:203–209

    Google Scholar 

  55. Millar JA, McLean K, Reid JL (1981) Calcium antagonists decrease adrenal and vascular responsiveness to angiotensin II (A II) in normal man. 8th Scientific Meeting of the Int Soc Hypert, Milan. Abstract 292

  56. Nobile-Orazio E, Sterzi R (1981) Cerebral ischaemia after nifedipine treatment. Br Med J 283:948

    Google Scholar 

  57. Olivari MT, Bartorelli C, Polese A, Fiorentine C, Moruzzi P, Guazzi MD (1979) Treatment of hypertension with nifedipine, a calcium antagonistic agent. Circulation 59:1056–1062

    Google Scholar 

  58. Opie LH, White DA (1980) Adverse interaction between nifedipine andβ-blockade. Br Med J 280:1462

    Google Scholar 

  59. Opie LH (1980) Calcium antagonists. Lancet I:806–810

    Google Scholar 

  60. Osada T, Kajiwara N, Kobayashi Y, Murakami A, Hashida J, Ono M, Kita T, Tei T, Fugibayashi Y, Yamamoto Y, Kuniyoshi K, Shimoda K, Hatano M (1980) The inhibition of hypertension and the changes of the humoral factors in SHR treated with diltiazem. Jap Heart J 21:581

    Google Scholar 

  61. Polese A, Fiorentini C, Olivari MT, Guazzi MD (1979) Clinical use of a calcium antagonistic agent (nifedipine) in acute pulmonary edema. Am J Med 66:825–830

    Google Scholar 

  62. Robson RH, Vishwanath MC (1982) Nifedipine and beta-blockade as a cause of cardiac failure. Br Med J 284:104

    Google Scholar 

  63. Rosenthal J (1982) Kalzium-Antagonisten in der Differentialtherapie der arteriellen Hypertonie. Münch Med Wochenschr 124:Nr 47, 1047–1050

    Google Scholar 

  64. Röjdmark S, Andersson DEH, Hed R, Nordland A, Sanelblad L, Wiechel KL (1981) Does verapamil influence glucose-induced insulin release in man? Acta Med Scand 210:501–505

    Google Scholar 

  65. Ruskoaho H (1980) Antihypertensive effect of long-term treatment with verapamil in spontaneous hypertension in rats. Naunyn Schmiedebergs Arch Pharmacol 313 [Suppl R]:36

    Google Scholar 

  66. Singh BN, Ellrodt G, Peter CT (1978) Verapamil: A review of its pharmacological properties and therapeutic use. Drugs 15:169–197

    Google Scholar 

  67. Spies HF, Koch M, Appel E, Palm D, Kaltenbach M (1978) Einfluß oraler Langzeittherapie mit Verapamil und Metoprolol auf arteriellen Blutdruck, Herzfrequenz und Plasmakatecholamine bei Hypertonikern. Z Kardiol 67:196–201

    Google Scholar 

  68. Staffurth JS, Emery P (1981) Adverse interaction between nifedipine and beta-blockade. Br Med J 282:225

    Google Scholar 

  69. Starke K, Schūmann HJ (1973) Die Wirkung von Nifedipine auf die Funktion der sympathischen Nerven des Herzens. Arzneim Forsch (Drug Res) 23:193–197

    Google Scholar 

  70. Vater W, Kroneberg G, Hoffmeister F, Kaller H, Meng K, Oberdorf A, Puls W, Schlossmann K (1972) Zur Pharmakologie von 4-(2'Nitrophenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarbonsäuredimethylester (Nifedipin, Bay a 1040). Arzneim Forsch (Drug Res) 22:1–14

    Google Scholar 

  71. Witzleben HV, Frey M, Keidel JA, Fleckenstein A (1980) Normalization of blood pressure in spontaneously hypertensive rats by long-term oral treatment with verapamil and nifedipine. Pflügers Arch [Suppl 384]:R9

  72. Yorifuji S, Kawai Y, Arami S (1979) Hypotensive effect of diltiazem hydrochloride (Herbesser tablets) in patients with essential hypertension. J Adult Disease 9:893–907

    Google Scholar 

  73. Zidek W, Losse H, Dorst KG, Zumkley H, Vetter H (1982) Intracellular sodium and calcium in essential hypertension. Klin Wochenschr 60:859–862

    Google Scholar 

  74. Ziegler R, Grundei P (in Vorbereitung)

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  1. Nephrologische Abteilung der Medizinischen Universitätsklinik, Universität Würzburg, Germany

    A. Heidland, E. Heidbreder, W. H. Hörl & R. M. Schäfer

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  1. A. Heidland
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Herrn Professor Dr. F. Gross zur Vollendung seines 70. Geburtstages gewidmet.

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Heidland, A., Heidbreder, E., Hörl, W.H. et al. Calciumantagonisten in der Therapie der Hypertonie. Klin Wochenschr 61, 633–640 (1983). https://doi.org/10.1007/BF01487579

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