Advertisement

European Journal of Clinical Pharmacology

, Volume 29, Issue 2, pp 149–154 | Cite as

Antihypertensive and metabolic effects of nifedipine and labetalol alone and in combination in primary hypertension

  • K. P. Öhman
  • L. Weiner
  • H. von Schenck
  • B. E. Karlberg
Originals

Summary

In a randomised, double-blind, cross over trial, 25 patients with mild to moderate primary hypertension were given nifedipine 20–40 mg twice daily and labetalol 200–400 mg twice daily after a 4 week period on placebo, followed by the two drugs in combination. The BP during placebo therapy was 164/108 mmHg supine and 159/110 mmHg standing. After monotherapy with nifedipine for 6 weeks the supine BP was reduced by 18/13 mmHg and the standing BP by 20/12 mmHg; with labetalol the corresponding figures were 26/15 mmHg and 28/21 mmHg, respectively. The combined therapy induced a larger fall in BP, by 36/22 mmHg supine and by 39/24 mmHg standing; in 21 of 23 patients the BP became normal. The heart rate (HR) decreased during labetalol treatment alone and on the combined therapy. With nifedipine alone, the HR was unchanged in the supine position and increased on standing. Nifedipine increased plasma renin activity (PRA) and urinary aldosterone excretion (uA), whereas labetalol reduced both. During combination therapy, PRA and uA remained unchanged. There was a slight fall in HDL-cholesterol during treatment with labetalol alone and in combination with nifedipine. The fasting blood glucose increased slightly during treatment with each of the drugs, but neither caused a change in the concentrations of glycosylated haemoglobin A1, serum insulin, C-peptide, or plasma glucagon. Adverse effects as a rule were well tolerated and were related to the pharmacological effects of the drugs. Only 2 patients left the trial, both during labetalol treatment.

Key words

nifedipine labetalol primary hypertension calcium channel blockade alpha- and beta-adrenergic blockade renin-angiotensin system glucose homeostasis HDL-cholesterol 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Aoki K, Yoshida T, Kato S, Tazume K, Soto I, Takikawa K, Hotta K (1976) Hypotensive action and increased plasma renin activity by calcium antagonist (nifedipine) in hypertensive patients. Jap Heart J 17: 479–484Google Scholar
  2. 2.
    Bhatnagar SK, Amin MMA, Al-Yusuf AR (1984) Diabetogenic effects of nifedipine. Br Med J 289: 19Google Scholar
  3. 3.
    Brown RD, Swander A, McKenzie JK (1976) Urine aldosterone radioimmunoassay: validation of a method without chromatography. J Clin Endocrinol 42: 894–900Google Scholar
  4. 4.
    Bühler FR, Hulthén UL, Kiowski W, Bolli P (1982) Greater antihypertensive efficacy of the calcium channel inhibitor verapamil in older and low renin patients. Clin Sci 63 [Suppl 8]: 439s-442sGoogle Scholar
  5. 5.
    Charles S, Ketelslegers J-M, Buysschaert M, Lambert AE (1981) Hyperglycemic effect of nifedipine. Br Med J 283: 19–20Google Scholar
  6. 6.
    Corea L, Miele N, Bentivoglio M, Boschetti E, Agabiti-Rosei EI, 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: 115s-117sGoogle Scholar
  7. 7.
    Ferrari A, Buccino N, DiRienzo M, Pedotti A, Mancia G, Zanchetti A (1981) Labetalol and 24-hour monitoring of arterial blood pressure in hypertensive patients. J Cardiovasc Pharmacol 3 [Suppl 1]: 542–552Google Scholar
  8. 8.
    Fray JCS (1980) Stimulus-secretion coupling of renin. Role of hemodynamic and other factors. Circ Res, 47: 485–492Google Scholar
  9. 9.
    Frick MH, Pörsti P (1976) Combined alpha- and beta-adrenoceptor blockade with labetalol in hypertension. Br Med J 272: 1046–1048Google Scholar
  10. 10.
    Fyhrquist F, Soveri P, Puutula L, Stenman UH (1976) Radioimmunoassay of plasma renin activity. Clin Chem 22: 250–256Google Scholar
  11. 11.
    Giugliano D, Torella R, Cacciapuoti F, Gentile S, Verza M, Varriecho M (1980) Impairment of insulin secretion in man by nifedipine. Eur J Clin Pharmacol 18: 395–398Google Scholar
  12. 12.
    Gomez G (1982) The effect of different antihypertensive therapies on plasma lipids. Practitioner 226: 985–991Google Scholar
  13. 13.
    Greenwood RH (1982) Hyperglycemic effect of nifedipine. Br Med J 284: 50Google Scholar
  14. 14.
    Guazzi MD, Fiorentini C, Olivari M, Bartorelli C, Necchi C, Polese A (1980) Short and long-term efficacy of a calcium antagonist agent (nifedipine) combined with methyldopa in the treatment of severe hypertension. Circulation 61: 913–919Google Scholar
  15. 15.
    Hansson L, Hähnel B (1976) Labetalol, a new alpha- and beta-adrenoceptor blocking agent, in hypertension. Br J Clin Pharmacol 3 [Suppl 3]: 763–764Google Scholar
  16. 16.
    Harrower ADB, Donnelly T (1981) Hyperglycemic effect of nifedipine. Br Med J 283: 796Google Scholar
  17. 17.
    Heding LG (1975) Radioimmunological determination of human C-peptide in serum. Diabetologia 11: 541–548Google Scholar
  18. 18.
    Hellman B (1975) The significance of calcium for glucose stimulation of insulin release. Endocrinology 97: 392–398Google Scholar
  19. 19.
    Holm G (1983) Adrenergic regulation of insulin release. Acta Med Scand 672 [Suppl]: 21–25Google Scholar
  20. 20.
    Hornung RS, Gould BA, Jones RJ, Sonecha TN, Raftery EB (1983) Nifedipine tablets for systemic hypertension: A study using continuous ambulatory intraarterial recording. Am J Cardiol 51: 1323–1327Google Scholar
  21. 21.
    Juhlin-Dannfelt A (1982) Metabolic effects of beta-adrenoceptor blockade on skeletal muscle at rest and during exercise. Acta Med Scand 665 [Suppl]: 113–115Google Scholar
  22. 22.
    Koch G (1979) Cardiovascular dynamics after acute and long term alpha- and beta-adrenoceptor blockade at rest, supine and standing, and during exercise. Br J Clin Pharmacol 8 [Suppl 2]: 101s-105sGoogle Scholar
  23. 23.
    Levy GP, Richards DA (1980) Labetalol. In: Scriabine A (ed) Pharmacology of antihypertensive drugs. Raven Press, New York, 325–347Google Scholar
  24. 24.
    Lund-Johansen P (1980) State of the art review. Hemodynamics in essential hypertension. Clin Sci 59: 343s-354sGoogle Scholar
  25. 25.
    McGonigle RJS, Williams L, Murphy MJ, Parsons V (1981) Labetalol and lipids. Lancet 1: 163Google Scholar
  26. 26.
    Opie LH, White DA (1980) Adverse interaction between nifedipine and beta-blockade. Br Med J 281: 1462–1463Google Scholar
  27. 27.
    Pedersen OL, Mikkelsen E (1978) Acute and chronic effects of nifedipine in arterial hypertension. Eur J Clin Pharmacol 14: 375–381Google Scholar
  28. 28.
    Pedersen OL, Mikkelsen E, Christensen NJ, Kornerup HJ, Pedersen EB (1979) Effect of nifedipine on plasma renin, aldosterone and catecholamines in arterial hypertension. Eur J Clin Pharmacol 15: 235–240Google Scholar
  29. 29.
    Prichard BNC, Boakes AJ (1976) Labetalol in long-term treatment of hypertension. Br J Clin Pharmacol 3 [Suppl 3]: 743–750Google Scholar
  30. 30.
    Rowland E, Evans T, Krikler D (1979) Effect of nifedipine on atrioventricular conduction as compared with verapamil. Br Heart J 42: 124–127Google Scholar
  31. 31.
    von Schenck H, Nilsson OR (1981) Radioimmunoassay of extracted glucagon compared with three non-extraction assays. Clin Chim Acta 109: 183–191Google Scholar
  32. 32.
    Thibonnier M, Bonnet F, Corvol P (1980) Antihypertensive effect of fractionated sublingual administration of nifedipine in moderate essential hypertension. Eur J Clin Pharmacol 17: 161–164Google Scholar
  33. 33.
    Thulin T, Henningsen NC, Karlberg BE, Nilsson OR (1981) Clinical and metabolic effects of labetalol compared with atenolol in primary hypertension. Curr Ther Res 30: 194–204Google Scholar
  34. 34.
    Uusitupa M, Siitonen O, Härkönen M, Gordin A, Aro A, Hersio K, Johansson G, Korhonen T, Raurama R (1982) Metabolic and hormonal response to physical exercise during betal-selective and non-selective beta-blockade. Hormon Metab Res 14: 583–589Google Scholar
  35. 35.
    Valdès G, Soto ME, Croxatto H, Bellolio T, Corbalan R, Casanegra P (1982) Effects of nifedipine during low, normal and high intakes of sodium in patients with essential hypertension. Clin Sci 63 [Suppl 8]: 447s-450sGoogle Scholar
  36. 36.
    Wallin JD, O'Neil WM (1983) Labetalol — Current research and therapeutic status. Arch Intern Med 143: 485–490Google Scholar
  37. 37.
    Weidmann P, Chatel R, Ziegler WH, Flammer J, Reubi FC (1978) Alpha- and beta-adrenergic blockade with orally administered labetalol in hypertension. Am J Cardiol 41: 570–576Google Scholar
  38. 38.
    Zezulka AV, Gill JS, Beevers DG (1984) Diabetogenic effects of nifedipine. Br Med J 289: 437–38Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • K. P. Öhman
    • 1
  • L. Weiner
    • 3
  • H. von Schenck
    • 2
  • B. E. Karlberg
    • 1
  1. 1.Departments of Internal MedicineHypertension-Endocrine UnitLinköpingSweden
  2. 2.Clinical ChemistryUniversity HospitalLinköpingSweden
  3. 3.Department of Internal MedicineCounty HospitalKarlskogaSweden

Personalised recommendations