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. 1984 Dec;18(6):817–822. doi: 10.1111/j.1365-2125.1984.tb02550.x

Influence of atenolol and nifedipine on digoxin-induced inotropism in humans.

P B Hansen, J Buch, O O Rasmussen, S Waldorff, E Steiness
PMCID: PMC1463669  PMID: 6529522

Abstract

Short term effect of digoxin on left ventricular performance was studied in six healthy volunteers before and during atenolol or nifedipine administration. Left ventricular function was evaluated by systolic time intervals and echocardiography. No changes in left ventricular end diastolic or systolic dimensions occurred throughout the study, indicating unchanged ventricular pre- and afterload. Thus, changes in the systolic time intervals must be attributed to changes in cardiac contractility. Changes in the pre-ejection period index (PEPI) obtained from the systolic time intervals were used as a measure of digoxin-induced inotropism. A concentration-response relationship between plasma digoxin level and changes in PEPI was revealed when digoxin was given alone. Atenolol did not influence the digoxin-induced inotropism at a given serum digoxin level. During nifedipine administration no inotropic effect of digoxin could be demonstrated. Thus, it is concluded that nifedipine attenuates digoxin-induced inotropism, while atenolol seems without this effect. These results are in accordance with previous experiments and reflect the different pharmacological sites of action of beta-adrenoceptor antagonists and calcium channel blocking agents. Plasma digoxin concentration, renal digoxin clearance and creatinine clearance did not change during atenolol or nifedipine.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Belz G. G., Aust P. E., Munkes R. Digoxin plasma concentrations and nifedipine. Lancet. 1981 Apr 11;1(8224):844–845. doi: 10.1016/s0140-6736(81)92727-6. [DOI] [PubMed] [Google Scholar]
  2. Braunwald E. Mechanism of action of calcium-channel-blocking agents. N Engl J Med. 1982 Dec 23;307(26):1618–1627. doi: 10.1056/NEJM198212233072605. [DOI] [PubMed] [Google Scholar]
  3. Buch J., Egeblad H., Hansen P. B., Kjaergård H., Waldorff S., Steiness E. Correlation between changes in systolic time intervals and left ventricular end-diastolic diameter after preload reduction. Non-invasive monitoring of pharmacological intervention. Br Heart J. 1980 Dec;44(6):668–671. doi: 10.1136/hrt.44.6.668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buch J., Waldorff S. Classical concentration-response relationship between serum digoxin level and contractility indices. Dan Med Bull. 1980 Dec 6;27(6):287–290. [PubMed] [Google Scholar]
  5. Buch J., Waldorff S., Hansen P. B., Rasmussen O. O. Non-invasive measuring of the circulatory effect of afterload reduction in order to monitor the pharmacodynamic effect of drugs in normal volunteers. Br Heart J. 1983 Aug;50(2):170–175. doi: 10.1136/hrt.50.2.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cantelli I., Pavesi P. C., Parchi C., Naccarella F., Bracchetti D. Acute hemodynamic effects of combined therapy with digoxin and nifedipine in patients with chronic heart failure. Am Heart J. 1983 Aug;106(2):308–315. doi: 10.1016/0002-8703(83)90197-7. [DOI] [PubMed] [Google Scholar]
  7. Cokkinos D. V., Demopoulos J. N., Heimonas E. T., Vorides E. M. Influence of digitalis on cardiac function before and after autonomic blockade. Acta Cardiol. 1978;33(3):185–194. [PubMed] [Google Scholar]
  8. Crawford M. H., LeWinter M. M., O'Rourke R. A., Karliner J. S., Ross J., Jr Combined propranolol and digoxin therapy in angina pectoris. Ann Intern Med. 1975 Oct;83(4):449–455. doi: 10.7326/0003-4819-83-4-449. [DOI] [PubMed] [Google Scholar]
  9. Garrard C. L., Jr, Weissler A. M., Dodge H. T. The relationship of alterations in systolic time intervals to ejection fraction in patients with cardiac disease. Circulation. 1970 Sep;42(3):455–462. doi: 10.1161/01.cir.42.3.455. [DOI] [PubMed] [Google Scholar]
  10. Klugmann S., Salvi A., Camerini F. Haemodynamic effects of nifedipine in heart failure. Br Heart J. 1980 Apr;43(4):440–446. doi: 10.1136/hrt.43.4.440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Koch-Weser J. Beta-receptor blockade and myocardial effects of cardiac glycosides. Circ Res. 1971 Feb;28(2):109–118. doi: 10.1161/01.res.28.2.109. [DOI] [PubMed] [Google Scholar]
  12. Matsumoto S., Ito T., Sada T., Takahashi M., Su K. M., Ueda A., Okabe F., Sato M., Sekine I., Ito Y. Hemodynamic effects of nifedipine in congestive heart failure. Am J Cardiol. 1980 Sep;46(3):476–480. doi: 10.1016/0002-9149(80)90018-1. [DOI] [PubMed] [Google Scholar]
  13. Mikkelsen E., Andersson K. E., Pedersen O. L. Effects of digoxin on isolated human peripheral arteries and veins. Acta Pharmacol Toxicol (Copenh) 1979 Oct;45(4):249–256. doi: 10.1111/j.1600-0773.1979.tb02390.x. [DOI] [PubMed] [Google Scholar]
  14. Oeff M., Beck O. A., Hochrein H. Einfluss von Digitalis auf die Pindolol-Wirkung bei Koronarkranken mit Belastungsherzinsuffizienz. Dtsch Med Wochenschr. 1979 Jan 19;104(3):98–103. doi: 10.1055/s-0028-1103852. [DOI] [PubMed] [Google Scholar]
  15. Pedersen K. E., Dorph-Pedersen A., Hvidt S., Klitgaard N. A., Kjaer K., Nielsen-Kudsk F. Effect of nifedipine on digoxin kinetics in healthy subjects. Clin Pharmacol Ther. 1982 Nov;32(5):562–565. doi: 10.1038/clpt.1982.203. [DOI] [PubMed] [Google Scholar]
  16. Quinones M. A., Gaasch W. H., Cole J. S., Alexander J. K. Echocardiographic determination of left ventricular stress-velocity relations. Circulation. 1975 Apr;51(4):689–700. doi: 10.1161/01.cir.51.4.689. [DOI] [PubMed] [Google Scholar]
  17. Waldorff S., Hansen P. B., Kjaergård H., Buch J., Egeblad H., Steiness E. Amiloride-induced changes in digoxin dynamics and kinetics: abolition of digoxin-induced inotropism with amiloride. Clin Pharmacol Ther. 1981 Aug;30(2):172–176. doi: 10.1038/clpt.1981.144. [DOI] [PubMed] [Google Scholar]
  18. Weissler A. M., Harris W. S., Schoenfeld C. D. Systolic time intervals in heart failure in man. Circulation. 1968 Feb;37(2):149–159. doi: 10.1161/01.cir.37.2.149. [DOI] [PubMed] [Google Scholar]

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