Summary
Intravenous nicardipine, 5 mg, was administered in two comparable groups of eight patients with chronic coronary artery disease but no clinical signs of heart failure. One group had received no previous treatment and served as a control group, and the other had received long-term treatment with large oral doses of propranolol. Blood concentrations of nicardipine were higher, and the area under the plasma concentration curve was greater in the group previously treated by propranolol. The total clearance of nicardipine was decreased in patients taking propranolol, without a change in the half-life of the drug. Typical hemodynamic responses, namely, a decrease in aortic pressure and in arterial resistances, were greater and more lasting in patients previously treated orally by propranolol. Filling pressure remained stable in both groups. The nicardipine infusion did not induce signs of dromotropic or inotropic negative effects in either group. The greater and more lasting hemodynamic effects of nicardipine in the group previously treated orally by propranolol do not seem to be related to an overall hemodynamic action of propranolol, but are probably due to higher nicardipine plasma levels, and may be caused by a decrease in hepatic blood flow induced by propranolol, with a consequent decrease in nicardipine clearance and by a smaller nicardipine volume of distribution in the propranolol group.
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References
Ryden L, Saetre H. The haemodynamic effect of verapamil.Eur J Clin Pharmacol 1971:3:153–157.
Atterhög JH, Ekelund LG, Haemodynamic effects of intravenous verapamil at rest and during exercise in subjectively healthy middle-aged men.Eur J Clin Pharmacol 1975; 8:317–322.
Robson RH, Wishwanath MC, Nifedipine and beta blockade as a cause of cardiac failure.Br Med J 1982;294:104.
Opie LH, White DA, Adverse interaction between nifedipine and beta blockade.Br Med J 1980;281:1462.
Rousseau MF, Etienne J, Van Mechelen H, et al. Hemodynamic and cardiac effects of nicardipine in patients with coronary artery disease.J Cardiorase Pharmacol 1984;6:833–839.
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.
Leon M, Rosing D, Bonow R, et al. Combination therapy with calcium-channel blockers and beta-blockers for chronic stable angina pectoris.Am J Cardiol 1985;55:69B-80B.
Dow RJ, Graham DJM. A review of the human metabolism and pharmacokinetics of nicardipine hydrochloride.Br J Clin Pharmacol 1986:22:195S-202S.
Parker G, Danheshmed TK, Roberts JC. Do beta blockers differ in their effects on hepatic microsomal enzymes and liver blood flow?J Clin Pharmacol 1984;24:493–499.
Dodge HT, Determination of left ventricular volume and mass.Radiol Clin North Am 1971;9:459–467.
Grunk-Emeier GL, Burg BA, Anderson RP, A simple method for calculating Vmax.Clin Res 1973;31:422.
Wu A, Massey I, Kushinsky S, Capillary column gas chromatographic method using electron capture detection for the simultaneous determination of nicardipine and its pyridine metabolite in plasma.J Chromatog 1987;415:65–73.
Gomeni R. PHARM. An interactive program for individual and population pharmacokinetic parameter estimation.Comput Biol Med 1984;14:25–34.
Perrier D, Mayersohn M. Noncompartmental determination of the steady-state volume of distribution for any mode of administration.J Pharm Sci 1982;71:372–373.
Pang KS, Rowland M. Hepatic clearance of drugs. I. Theoretical considerations of a “well-stirred” model and a “parallel tube” model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance.J Pharmacokin Biopharm 1977;5:625–653.
Gibson DG. Pharmacodynamic properties of β-adrenergic receptor blocking drugs in man.Drugs 1974;7:8–38
Kleinbloesem CH. Van Brummelen P, Sandberg TWH, et al. Kinetic and hemodynamic interactions between nifedipine and propranolol in healthy subjects utilizing controlled rates of drug input. In: Nifedipine, clinical pharmacokinetics and hemodynamic effects, PhD. Thesis, Gravenhage Netherlands, pp. 151–166.
Kendall MJ, Jack DB, Laugher SJ, et al. Lack of a pharmacokinetic interaction between nifedipine and the β-adrenoceptor blockers, metoprolol and atenolol.Br J Clin Pharmacol 1984:18:331–335.
Epstein SE, Branwald E, Beta-adrenergic receptor blocking drugs: Mechanism of action and clinical applications.N Engl J Med 1966:275:1106.
Ulrich M, Frochlich ED, Dustan AP, et al. Immediate hemodynamic effects of beta-adrenergic blockade with propranolol in normotensive man.Circulation 1968;37:411–416.
Tarazi RC, Dustan HP, Beta-adrenergic blockade in hypertension.Am J Cardiol 1972;29:633–640.
Tarazi RC, Dustan HP, Bravo EL, Haemodynamic effects of propranolol in hypertension: A review.Postgrad Med J 1976;52(Suppl 4):92–100.
Lambert CR, Hill JA, Feldman RL, et al. Effects of nicarlipine on left ventricular function and energetics in man.Int J Cardiol 1986;10:237–249.
Berland J, Savin T, Cribier A, et al. Effects of low dose nicardipine on systemic and coronary hemodynamics during rapid atrial pacing in patients with ischemic heart disease.J Am Coll Cardiol 1986;7:179A.
Winniford MD, Markham RV, Firth BG, et al. Hemodynamic and electrophysiologic effects of verapamil and nifedipine in patients on propranolol.Am J. Cardiol 1982:50:704–710.
Hung J, Lamb IH, Conally 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.
Rocha P, Baron B, Delestrain A, et al. Hemodynamic effects of intravenous diltiazem in patients treated chronically with propranolol.Am Heart J 1986;111:62–68.
Rowland E, Razis P, Sugrue D, et al. Acute and chronic haemodynamic and electrophysiological effects of nifedipine in patients receiving atenolol.Br Heart J 1983:50:383–389.
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.
Oesterle SN, Alderman EL, Beier-Scott L, et al. Diltiazem and propranolol combination: Hemodynamic effects following acute intravenous administration.Am Heart J 1986; 111:489–497.
Josh PI, Dalal JJ, Ruttley MSJ, et al. Nifedipine and left ventricular function in beta-blocked patients.Br Heart J 1981;45:457–459.
Visioli O, Bolognesi R, Cucchini F, et al. The effects of intravenous nifedipine on cardiac hemodynamics and contractility in patients with coronary artery disease in the presence or absence of beta adrenergic blockade.Cardiocase Drugs Ther 1987;1:353–358.
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Rocha, P., Guerret, M., David, D. et al. Kinetics and hemodynamic effects of intravenous nicardipine modified by previous propranolol oral treatment. Cardiovasc Drug Ther 4, 1525–1532 (1990). https://doi.org/10.1007/BF02026502
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DOI: https://doi.org/10.1007/BF02026502