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The Pharmacology of the Cardiac Glycosides

  • Theodore M. Brody
  • Tai Akera
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 34)

Abstract

The term digitalis encompasses a wide variety of steroids which have the property of increasing the force of contraction and eliciting characteristic electrophysiologic effects upon the heart. These substances are derived from a number of plant and animal sources. The medicinal actions of the squill, or sea onion, were recognized as early as 1600 B.C. Digitalis-like activity is present in the seeds of strophanthus gratus, which is the source of ouabain, used as an African arrow poison and in the skin of the toad, used by ancient Chinese herbalists. The glycosides most frequently used today are derived from the leaves of the foxglove, Digitalis purpurea and D. lanata. The classic study on the action of digitalis was published in 1785 by William Withering who described his long experience with digitalis in An Account of the Foxglove, and Some of Its Medicinal Uses: With Practical Remarks on Dropsy, and other Diseases {1}. Withering failed to recognize that its efficacy in reducing edema was secondary to its cardiac action. A second comprehensive monograph was published in 1799 by John Ferrier, who suggested that digitalis might have a cardiac effect distinct from its ability to promote a diuresis. Traube in 1850 also recognized the effect of digitalis in promoting the efficiency of cardiac muscle and further suggested that the bradycardia was the result of vagal stimulation.

Keywords

Atrial Flutter Cardiac Glycoside Positive Inotropic Effect Sodium Pump Purkinje Fiber 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Withering W: An account of the foxglove and some of its medicinal uses: with practical remarks on dropsy and other diseases. CGJ and J Robison, 1784. Reprinted in Med Class 2: 305–443, 1937.Google Scholar
  2. 2.
    Cattell M, Gold H: The influence of digitalis glycosides on the force of contraction of mammalian cardiac muscle. J Pharmacol Exp Ther 62: 116–125, 1938.Google Scholar
  3. 3.
    Chen KK, Henderson FG: Pharmacology of sixty-four cardiac glycosides and aglycones. J Pharmacol Exp Ther 111: 365–383, 1954.PubMedGoogle Scholar
  4. 4.
    Thomas R, Brown L, Gelbart A: The digitalis receptor: inferences from structure activity relationships. Circ Res (Suppl 1) 46: 167–172, 1980.Google Scholar
  5. 5.
    Tamm C: The stereochemistry of the glycosides in relation to biological activity. In: Wellbrandt W, Lindgren P (eds) Proceedings of the First International Pharmacological Meeting. Vol 3: Newer aspects of cardiac glycosides. Oxford: Pergamon, 1963, pp 11–26.Google Scholar
  6. 6.
    Schwartz A, Lindenmayer GE, Allen JC: The sodium—potassium adenosine triphosphatase: pharmacological, physiological and biochemical aspects. Pharmacol Rev 27: 3–134, 1975.PubMedGoogle Scholar
  7. 7.
    Goldman RH, Coltart DJ, Schweizer E, Snidow G, Harrison DC: Dose response in vivo to digoxin in normo-and hyperkalaemia-associated biochemical changes. Cardiovasc Res 9: 515–523, 1975.PubMedCrossRefGoogle Scholar
  8. 8.
    Akera T, Brody TM: The role of Na+,K+-ATPase in the inotropic action of digitialis. Pharmacol Rev 29: 187–220, 1977.PubMedGoogle Scholar
  9. 9.
    Tobin T, Brody TM: Rates of dissociation of enzyme—ouabain complexes and K0, values in (Na+ + K+) adenosine-triphosphatase from different species. Biochem Pharmacol 21: 1553–1560, 1972.PubMedCrossRefGoogle Scholar
  10. 10.
    Mason DT: Regulation of cardiac performance in clinical heart disease: interactions between contractile state mechanical abnormalities and ventricular compensatory mechanisms. Am J Cardiol 32: 437–448, 1973.PubMedCrossRefGoogle Scholar
  11. 11.
    Tsien RW, Weingart R, Kass RS: Digitalis: isotropic and arrhythmogenic effects on membrane currents in cardiac Purkinje fibers. In: Morad M (ed) Biophysical aspects of cardiac muscle. New York: Academic, 1978, pp 345–368.CrossRefGoogle Scholar
  12. 12.
    Gillis RA, Quest JA: The role of the nervous system in the cardiovascular effects of digitalis. Pharmacol Rev 31: 19–97, 1979.PubMedGoogle Scholar
  13. 13.
    Doering W: Quinidine—digoxin interaction: pharmacokinetics, underlying mechanism and clinical implications. N Engl J Med 301: 400–404, 1979.PubMedCrossRefGoogle Scholar
  14. 14.
    Beller GA, Smith TW, Abelmann WH, Haber E, Hood WB: Digitalis intoxication: a prospective clinical study with serum level correlations. N Engl J Med 284: 989–997, 1971.PubMedCrossRefGoogle Scholar
  15. 15.
    Cattel M, Gold H: Studies on purified digitalis glucosides. III. The relationship between therapeutic and toxic potency. J Pharmacol Exp Ther 71: 114–125, 1941.Google Scholar
  16. 16.
    Akera T: Effects of cardiac glycosides on Na+,K+ATPase. In: Greeff K (ed) Handbook of experimental pharmacology. Vol. 56/I: Cardiac glycosides. Heidelberg: Springer-Verlag, 1981, pp 288–336.Google Scholar
  17. 17.
    Akera T, Baskin SI, Tobin T, Brody TM: Ouabain: temporal relationship between the inotropic effect and the in vitro binding to, and dissociation from, (Na+ + K+)-activated ATPase. Naunyn Schmiedebergs Arch Pharmacol 277: 151–162, 1973.PubMedCrossRefGoogle Scholar
  18. 18.
    Allen DG, Blinks JR: Calcium transients in aequorin-injected frog cardiac muscle. Nature 273: 509–513, 1978.PubMedCrossRefGoogle Scholar
  19. 19.
    Langer GA: The intrinsic control of myocardial contraction—ionic factors. N Engl J Med 285: 1065 1071, 1971.Google Scholar
  20. 20.
    Reuter H: Exchange of calcium ions in the mammalian myocardium. Circ Res 34: 599–605, 1974.PubMedCrossRefGoogle Scholar
  21. 21.
    Lee KS, Klaus W: The subcellular basis for the mechanism of inotropic action of cardiac glycosides. Pharmacol Rev 23: 193–261, 1971.PubMedGoogle Scholar
  22. 22.
    Langer GA: Ion fluxes in cardiac excitation and contraction and their relation to myocardial contractility. Physiol Rev 48: 708–757, 1968.PubMedGoogle Scholar
  23. 23.
    Akera T: Membrane adenosinetriphosphatase: a digitalis receptor? Science 198: 569–574, 1977.PubMedCrossRefGoogle Scholar
  24. 24.
    Gervais A, Lane LK, Anner BM, Lindenmayer GE, Schwartz A: A possible molecular mechanisms of the action of digitalis: ouabain action on calcium binding to sites associated with a purified sodium—potassiumactivated adenosine triphosphatase from kidney. Circ Res 40: 3–14, 1977.CrossRefGoogle Scholar
  25. 25.
    Lullmann H, Peters T: Action of cardiac glycosides on the excitation—contraction coupling in heart muscle. Prog Pharmacol 2: 1–57, 1979.Google Scholar
  26. 26.
    Ferrier GR, Saunders JH, Mendez C: A cellular mechanism for the generation of ventricular arrhythmias by acetylstrophanthidin. Circ Res 32: 600–609, 1973.PubMedCrossRefGoogle Scholar
  27. 27.
    Weaver LC, Akera T, Brody TM: Digoxin toxicity: primary sites of drug action on the sympathetic nervous system. J Pharmacol Exp Ther 197: 1–9, 1976.PubMedGoogle Scholar
  28. 28.
    Lathers CM, Kelliher GJ, Roberts J, Beasley AB: Nonuniform cardiac sympathetic nerve discharge: mechanism for coronary occlusion and digitalis-induced arrhythmias. Circulation 57: 1058–1065, 1978.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1984

Authors and Affiliations

  • Theodore M. Brody
  • Tai Akera

There are no affiliations available

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