Cardiovascular Drugs and Therapy

, Volume 5, Issue 4, pp 681–687 | Cite as

Hemodynamic interactions of a new beta blocker, celiprolol, with nifedipine in angina pectoris

  • B. Silke
  • S. P. Verma
  • S. Guy
Angina and Ischemic Heart Disease


The hemodynamic consequences of blockade at both beta-adrenoceptors and slow calcium channels is of therapeutic importance for patients with angina pectoris. The hemodynamic interaction of a new cardioselective beta blocker, celiprolol, and nifedipine was examined in an acute hemodynamic study using three prospectively matched groups with angiographically confirmed coronary artery disease (n = 10/group). Patients were randomly allocated to intravenous celiprolol (8 mg), sublingual nifedipine (20 mg), or their combination. Rest and exercise (supine bicycle) hemodynamics were determined before and following each therapy. At rest, celiprolol did not alter pumping function; nifedipine reduced diastolic blood pressure and systemic vascular resistance index (SVRI), with a small increase in heart rate. Combination therapy reduced systemic arterial pressure and SVRI; heart rate and cardiac stroke volume index increased. During exercise celiprolol tended to reduce heart rate and cardiac index; nifedipine reduced exercise SVR and cardiac stroke work indices. Combination therapy reduced all components of blood pressure; cardiac stroke work and SVR indices fell. These hemodynamic data suggest that beta blockade with celiprolol may result in a slight depression of cardiac pumping during exercise; however, such effects are offset by the vasodilating actions of nifedipine (reflex sympathetic action offsetting cardiodepression). Thus the acute hemodynamic effects of this combination were seemingly safe in these patients; the longer term effects during maintained therapy should be further assessed.

Key Words

celiprolol nifedipine interaction between drugs angina 


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  1. 1.
    Sharma B, Taylor SH. Reversible left ventricular failure in angina pectoris.Lancet 1970;2:902–907.PubMedCrossRefGoogle Scholar
  2. 2.
    Sharma B, Goodwin JF, Raphael MJ, et al. Left ventricular angiography on exercise: A new method of assessing left ventricular function is ischaemic heart disease.Br Heart J 1976;38:59–70.PubMedCrossRefGoogle Scholar
  3. 3.
    Braunwald E. Control of myocardial oxygen consumption.Am J Cardiol 1971;27:416–432.PubMedCrossRefGoogle Scholar
  4. 4.
    Prichard BNC, Aellig WH, Richardson GA. The action of intravenous oxprenolol, practolol, propranolol and sotalol on acute exercise tolerance in angina pectoris; the effect on heart rate and the electrocardiogram.Postgrad Med J 1970;46:77–83.Google Scholar
  5. 5.
    Dehmer GJ, Falkoff M, Lewis SE, et al. Effect of oral propranolol on rest and exercise left ventricular ejection fraction, volumes and segmental wall motion in patients with angina pectoris. Assessment with equilibrium gated blood pool imaging.Br Heart J 1981;45:656–666.PubMedCrossRefGoogle Scholar
  6. 6.
    Reale A, Nigri A, Gioffre PA, Motolese M. Acute influence of different beta-blocking drugs upon left heart haemodynamics at rest and during exercise in patients with coronary heart disease.Eur Heart J 1981;2:101–109.Google Scholar
  7. 7.
    Taylor SH, Silke B, Lee PS, Hilail A. Haemodynamic doseresponse effects of intravenous beta-blocking drugs with different ancillary properties in patients with coronary heart disease.Eur Heart J 1982;3:564–569.PubMedGoogle Scholar
  8. 8.
    Taylor SH, Silke B, Lee PS. Intravenous beta-blockade in coronary heart disease: Is cardioselectivity or intrinsic sympathomimetic activity haemodynamically useful?N Engl J Med 1982;306:631–635.PubMedGoogle Scholar
  9. 9.
    Pittner H. Haemodynamic actions of celiprolol, a cardioselective beta-receptor blocker.Arzneimittelforsch 1983, 33(I):13–25.Google Scholar
  10. 10.
    Klein W, Fluch N, Brandt D. Comparative efficacy of a new cardioselective beta-adrenergic blocking agent celiprolol in stable angina: A placebo controlled double blind study.Wien Klin Wochenschr 1982;94(10):258–261.PubMedGoogle Scholar
  11. 11.
    Brodde OE, Daul A, Bock KD. The intrinsic sympathomimetic activity (ISA) of beta-adrenoreceptor (R) antagonists is not beta-R subtype selective.Naunyn-Schmiedebergs Arch Pharmac 1985;329:R 81.Google Scholar
  12. 12.
    Wolf PS, Smith RD, Khandwala A, et al. Celiprolol— pharmacological profile of an unconventional beta-blocker.Br J Clin Pract 1985;39(Suppl. 40):5–11.Google Scholar
  13. 13.
    Pittner H. Intrinsic sympathomimetic activity and its special features as exemplified by the beta-1-adrenoceptor blocker celiprolol.Wien Klin Wschr 1985;97:3–21.Google Scholar
  14. 14.
    Silke B, Verma SP, Frais MA, et al. Comparative effects of metoprolol and celiprolol on cardiac haemodynamics and left ventricular volume at rest and during exercise induced angina.Clin Pharmacol Ther 1986;39:5–15.PubMedGoogle Scholar
  15. 15.
    Silke B, Verma SP, Frais MA, et al. Differential actions of atenolol and celiprolol on cardiac performance in ischaemic heart disease.J Cardiovasc Pharmacol 1986;8(Suppl. 4):S132-S134.CrossRefGoogle Scholar
  16. 16.
    Atterhog JH, Ekelund LG, Myelin AL. Effect of nifedipine on exercise tolerance in patients with angina pectoris.Eur J Clin Pharmacol 1975;8:125–130.PubMedCrossRefGoogle Scholar
  17. 17.
    Moskowitz RM, Piccini PA, Nacarelli GY, Zelis R. Nifedipine therapy for stable angina pectoris: Preliminary results of effects on angina frequency and treadmill exercise response.Am J Cardiol 1979;44:811–816.PubMedCrossRefGoogle Scholar
  18. 18.
    Singh BN. Pharmacological basis for the therapeutic applications of slow-channel blocking drugs.Angiology 1982; 33:492–515.PubMedCrossRefGoogle Scholar
  19. 19.
    Stone PH, Antman EM, Muller JE, Braunwald E. Calcium channel blocking agents in the treatment of cardiovascular disorders. Part II: Hemodynamic effects and clinical applications.Ann Intern Med 1980;93:886–904.PubMedGoogle Scholar
  20. 20.
    Kieval J, Myerburg RJ. The hemodynamic effects of calcium channel blocking agents. A brief review.Angiology 1982;33:516–521.PubMedCrossRefGoogle Scholar
  21. 21.
    Silke B, Verma SP, Nelson GIC, et al. Haemodynamic dose-response effects of i.v. nicardipine in coronary artery disease.Br J Clin Pharmacol 1984;18:717–724.PubMedGoogle Scholar
  22. 22.
    Nelson GIC, Silke B, Ahuja RC, et al. The effect on left ventricular performance of nifedipine and metoprolol singly and together in exercise-induced angina pectoris.Eur Heart J 1984;5:67–79.PubMedGoogle Scholar
  23. 23.
    Silke B, Verma SP, Frais MA, et al. Haemodynamic analysis of the effects of nicardipine and metoprolol alone and in combination in coronary artery disease.Eur Heart J 1985;6:930–938.PubMedGoogle Scholar
  24. 24.
    Silke B. Verma SP, Midtbo KA, et al. A haemodynamic study of the effects of combined slow-calcium blockade (nisoldipine) and beta-blockade (metoprolol) in coronary artery disease.Int J Cardiol 1986;13:231–241.PubMedCrossRefGoogle Scholar
  25. 25.
    Verma SP, Nelson GIC, Jackson N, et al. Haemodynamic variability at rest and following repetitive upright dynamic exercise in coronary heart disease (abstract)Clin Sci 1984;66:52P.Google Scholar
  26. 26.
    Dixon WJ, Brown MB, eds.Biomedical computer programs ‘P’ series. Berkeley: University of California Press, 1979: 540.Google Scholar
  27. 27.
    Winer B J.Statistical principles in experimental design, 2nd ed. New York: McGraw-Hill, 1977:197–200.Google Scholar
  28. 28.
    Forrester JS, Ganz W, Diamond GA, et al. Thermodilution cardiac output determination with a single flow directed catheter.Am Heart J 1972;83:306–311.PubMedCrossRefGoogle Scholar
  29. 29.
    Hoel BL. Some aspects of the clinical use of thermodilution in measuring cardiac output. With particular reference to the Swan-Ganz thermodilution catheters.Scand J Clin Lab Invest 1978;48:383–388.CrossRefGoogle Scholar
  30. 30.
    Sorenson MB, Bille-Brahe NE, Engell HC. Cardiac output measurement by thermal dilution. Reproducibility and comparison with the dye-dilution technique.Ann Surg 1976; 183:67–72.CrossRefGoogle Scholar
  31. 31.
    Nelson GIC, Silke B, Ahuja R, et al. Haemodynamic effects of nifedipine during upright exercise in stable angina pectoris and either normal or severely impaired left ventricular function.Am J Cardiol 1984;53:451–455.PubMedCrossRefGoogle Scholar
  32. 32.
    Parker JO, West RO, Di Giorgi S. Hemodynmamic effects of propranolol in coronary heart disease.Am J Cardiol 1968;21:11–19.PubMedCrossRefGoogle Scholar
  33. 33.
    Hendry WG, Silke B, Taylor SH. Haemodynamic doseresponse effects of i.v. metoprolol in coronary heart disease.Eur J Clin Pharmacol 1981;19:323–327.PubMedCrossRefGoogle Scholar
  34. 34.
    Brodde OE, Schemuth R, Binkman M, et al. Betaadrenoceptor antagonists (non-selective as well as beta1 selective) with partial agonist activity decrease beta2 adrenoceptor density in human lymphocytes. Evidence for a beta2-agonist component of the partial agonist activity.Naunyn-Schmiedeberg’s Arch Pharmacol 1986;333:130–138.CrossRefGoogle Scholar
  35. 35.
    Daul A, Wang XL, Borchard U, et al. Differential changes in lymphocyte beta2-adrenoceptor density by beta-blocker administration. Role of intrinsic sympathomimetic activity.J Cardiovasc Pharmacol 1986;8(Suppl. 4):S93-S96.PubMedCrossRefGoogle Scholar
  36. 36.
    Tham TCK, Riddell JG, Shanks RG. The effect of increasing doses of celiprolol on sleeping heart rate and quality of sleep in man.Clin Pharmacol Ther, 1991;49:187.Google Scholar
  37. 37.
    Seabra-Gomes R, Rickards A, Sutton R. Haemodynamic effects of verapamil and practolol in man.Eur J Cardiol 1976;4:79–85.PubMedGoogle Scholar
  38. 38.
    Krikler DM, Spurrell RAJ. Verapamil in the treatment of paroxysmal supraventricular tachycardia.Postgrad Med J 1974;50:447–453.PubMedCrossRefGoogle Scholar
  39. 39.
    Kieval J, Kirsten EB, Kessler KM, et al. The effects of intravenous verapamil on hemodymamic status of patients with coronary artery disease receiving propranolol.Circulation 1982;65:653–659.PubMedGoogle Scholar
  40. 40.
    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.PubMedGoogle Scholar
  41. 41.
    Ludbrook PA, Tiefenbrunn AJ, Reed FR, Sobel BE. Acute haemodynamic responses to sublingual nifedipine: Dependence on left ventricular function.Circulation 1982;65: 489–498.PubMedGoogle Scholar
  42. 42.
    Klugmann S, Salvi A, Camerini F. Haemodynamic effects of nifedipine in heart failure.Br Heart J 1980;43:440–446.PubMedCrossRefGoogle Scholar
  43. 43.
    Joshi PI, Dalai JJ, Ruttley MSJ, et al. Nifedipine and left ventricular function in beta-blocked patients.Br Heart J 1981;45:457–459.PubMedCrossRefGoogle Scholar
  44. 44.
    Winniford MD, Markham RV, Jr., Firth BG, et al. Hemodynamic and electrophysiologic effects of verapamil and nifedipine in patients on propranolol.Am J Cardiol 1982;50: 704–710.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1991

Authors and Affiliations

  • B. Silke
    • 1
  • S. P. Verma
    • 1
  • S. Guy
    • 2
  1. 1.University Department of Cardiovascular Studies, and Department of Medical CardiologyThe General Infirmary at LeedsNorthern Ireland
  2. 2.Department of Therapeutics & Pharmacology, Whitla Medical BuildingQueen’s UniversityBelfastNorthern Ireland

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