Skip to main content

The pharmacology of cardiac glycosides

  • Chapter
Cardiac therapy

Abstract

The first systematic description of the use of digitalis was provided in 1785 by William Withering in his book An Account of the Foxglove and Some of its Medical Uses: With Practical Remarks on Dropsy and Other Diseases. Since that time digitalis has been used to treat a variety of illnesses including most forms of edema. In more recent times digitalis was used first to treat atrial fibrillation and then it was used to treat what we would now accept as heart failure. There have been a great many studies on the pharmacology of digitalis, but in spite of this it still is a frequent subject for investigation and there probably is much we still need to learn about its actions and mechanisms of action.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Gold H, Cattell M: Mechanism of digitalis action in abolishing heart failure. Arch Intern Med 65:263–278, 1940.

    CAS  Google Scholar 

  2. Ford LE: Effect of afterload reduction on myocardial energetics. Circ Res 46:161–166, 1980.

    PubMed  CAS  Google Scholar 

  3. Wilbrandt W: Zum Wirkungsmechanismus des Herzglykoside. Schweiz Med Wochenschr 85:315–320, 1955.

    PubMed  CAS  Google Scholar 

  4. Fozzard HA: Heart: excitation-contraction coupling. Ann Rev Physiol 39:201–210, 1977.

    CAS  Google Scholar 

  5. Gibbons WR, Fozzard HA: Relationships between voltage and tension in sheep cardiac Purkinje fibers. J Gen Physiol 65:345–365, 1975.

    PubMed  CAS  Google Scholar 

  6. Reuter H: Exchange of calcium ions in the mammalian myocardium. Circ Res 34:599–605, 1974.

    PubMed  Google Scholar 

  7. Blaustein MP: The interrelationship between sodium and calcium fluxes across cell membranes. Rev Physiol Biochem Pharmacol 70:33–82, 1974.

    PubMed  CAS  Google Scholar 

  8. Caroni P, Carafoli E: An ATP-dependent Ca2+-pumping system in dog heart sarcolemma. Nature 283:765–767, 1980.

    PubMed  CAS  Google Scholar 

  9. Pitts BJR, Stoichiometry of sodium-calcium exchange in cardiac sarcolemmal vesicles. J Biol Chem 254:6232–6235, 1979.

    PubMed  CAS  Google Scholar 

  10. Akera T, Brody TM: The role of Na+, K+-ATPase in the inotropic action of digitalis. Pharmacol Rev 29:187–188, 1977.

    PubMed  CAS  Google Scholar 

  11. Akera T, Larsen FS, Brody TM: Correlation of cardiac sodium- and potassium-activated adenosine triphosphatase activity with ouabain-induced inotropic stimulation. J Pharmacol Exp Ther 173:145–151, 1970.

    PubMed  CAS  Google Scholar 

  12. Besch HR Jr, Allen JC, Glick G, Schwartz A: Correlation between the inotropic action of ouabain and its effects on subcellular enzyme systems from canine myocardium. J Pharmacol Exp Ther 171:1–12, 1970.

    PubMed  CAS  Google Scholar 

  13. Goldman RH, Coltart JD, Friedman JP, Nola GT, Berke DK, Schweizer E, Harrison DC: The inotropic effects of digoxin in hyperkalemia. Relation to Na+, K+ ATPase inhibition in the intact animal. Circulation 48:830–838, 1973.

    PubMed  CAS  Google Scholar 

  14. Matsui H, Schwartz A: Mechanism of cardiac glycoside inhibition of the (Na+-K+)-dependent ATPase from cardiac tissue. Biochim Biophys Acta 151:655–663, 1968.

    PubMed  CAS  Google Scholar 

  15. Michael LH, Schwartz A, Wallick ET: Nature of the transport adenosine triphosphatase-digitalis complex: XIV. Inotropy and cardiac glycoside interaction with Na+, K+- ATPase of isolated cat papillary muscles. Mol Pharmacol 16:134–146, 1979.

    Google Scholar 

  16. Hougen TJ, Smith TW: Inhibition of myocardial cation active transport by subtoxic doses of ouabain in the dog. Circ Res 42:856–863, 1978.

    PubMed  CAS  Google Scholar 

  17. Miura DS, Rosen MR: The effects of ouabain on the transmembrane potentials and intracellular potassium activity of canine cardiac Purkinje fibers. Circ Res 42: 333–338, 1978.

    PubMed  CAS  Google Scholar 

  18. Deitmer JM, Ellis D: The intracellular sodium activity of cardiac Purkinje fibers during inhibition and reactivation of the Na-K pump. J Physiol 284:241–259, 1978.

    PubMed  CAS  Google Scholar 

  19. Wier WG: Calcium transients during excitation-concen-tration coupling in mammalian heart: aequorin signals of canine Purkinje fibers. Science 207:1085–1087, 1980.

    PubMed  CAS  Google Scholar 

  20. Marban E: Regulation of Calcium Current and Calcium Activity in Heart Cells. PhD Dissertation, Yale Univ, 1981.

    Google Scholar 

  21. Lee CO, Kang DH, Sokol JH, Lee KS: Relation between intracellular Na ion activity and tension of sheep cardiac Purkinje fibers exposed to dihydro-ouabain. Biophys J 29:315–330, 1980.

    PubMed  CAS  Google Scholar 

  22. Ellis D: The effects of external cations and ouabain on the intracellular sodium activity of sheep heart Purkinje fibers. J Physiol 273:211–240, 1977.

    PubMed  CAS  Google Scholar 

  23. Tsien RY, Rink TJ: Neutral carrier ion-selective microelectrodes for measurement of intracellular free calcium. Biochim Biophys Acta 599:623–638, 1980.

    PubMed  CAS  Google Scholar 

  24. Eisner DA, Lederer WJ: The relationship between sodium pump activity and twitch tension in cardiac Purkinje fibers. J Physiol 303:475–494, 1980.

    PubMed  CAS  Google Scholar 

  25. Eisner DA, Lederer WH, Vaughan-Jones RD: The dependence of sodium pumping and tension on intracellular sodium activity in voltage-clamped sheep Purkinje fibers. J Physiol 317:163–187, 1981.

    PubMed  CAS  Google Scholar 

  26. Eisner DA, Lederer WJ, Vaughan-Jones RD: Electrogenic sodium pumping in cardiac muscle: simultaneous measurement of intracellular sodium activity, membrane current and tension. J Physiol 300:42–43, 1980.

    Google Scholar 

  27. Michael L, Pitts BJR, Schwartz A: Is pump stimulation associated with positive inotropy of the heart? Science 200:1287–1289, 1978.

    PubMed  CAS  Google Scholar 

  28. Grupp G, Grupp IL, Ghysel-Burton J, Godfraind T, Schwartz A: Effects of very low concentrations of ouabain on contractile force of isolated guinea-pig, rabbit and cat atria and right ventricular papillary muscles: an interinstitutional study. J Pharmacol Exp Ther 220:145–151, 1981.

    Google Scholar 

  29. Knight RG, Nosek TM: Effects of rubidium on contractility and sodium pump activity in guinea-pig ventricle. J Pharmacol Exp Ther 219:573–579, 1981.

    PubMed  CAS  Google Scholar 

  30. Eisner DA, Lederer WJ, Vaughan-Jones RD: The effects of rubidium ions and membrane potential on the intracellular sodium activity of sheep Purkinje fibers. J Physiol 317:189–205, 1981.

    PubMed  CAS  Google Scholar 

  31. Akera T, Bennett RT, Olgaard MK, Brody TM: Cardiac Na+, K+-adenosine triphosphatase inhibition by ouabain and myocardial sodium: a computer simulation. J Pharmacol Exp Ther 199:287–297, 1976.

    PubMed  CAS  Google Scholar 

  32. Adams RJ, Schwartz A, Grupp G, Grupp I, Lee SW, Wallick ET: High-affinity ouabain binding site and low-dose positive inotropic effect in rat myocardium. Nature 296:167–171, 1982.

    PubMed  CAS  Google Scholar 

  33. Huang W, Rhee HM, Chiu TH, Askari A: Re-evaluation of the relationship between the positive inotropic effect of ouabain and its inhibitory effect on (Na+ + K+)-dependent adenosine triphosphatase in rabbit and dog hearts. J Pharmacol Exp Ther 211:571–581, 1979.

    PubMed  CAS  Google Scholar 

  34. Yamamoto S, Akera T, Kim DH, Brody TM: Tissue concentration of Na+, K+-adenosine triphosphatase and the positive inotropic action of ouabain in guinea-pig heart. J Pharmacol Exp Ther 217:701–707, 1981.

    PubMed  CAS  Google Scholar 

  35. Hess P, Müller P: Extracellular versus intracellular digoxin action on bovine myocardium, using a digoxin antibody and intracellular glycoside application. J Physiol 322:197–210, 1982.

    PubMed  CAS  Google Scholar 

  36. Kass RS, Tsien RW, Weingart R: Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibers. J Physiol 281:209–226, 1978.

    PubMed  CAS  Google Scholar 

  37. Marban E, Tsien RW: Ouabain increases the slow inward calcium current in ventricular muscle of the ferret. J Physiol 292:72–73P, 1979.

    Google Scholar 

  38. Marban E, Tsien RW: Is the slow inward calcium current of heart muscle inactivated by calcium? Biophys J 33:143, 1981.

    Google Scholar 

  39. Vassalle M, Karis J, Hoffman BF: Toxic effects of ouabain on Purkinje fibers and ventricular muscle fibers. Am J Physiol 203:433–439, 1962.

    PubMed  CAS  Google Scholar 

  40. Kassebaum DG: Electrophysiological effects of strophanthin in the heart. J Pharmacol Exp Ther 140:329–338, 1963.

    Google Scholar 

  41. Muller P: Ouabain effects on cardiac contraction, action potential and cellular potassium. Circ Res 17:46–56, 1965.

    Google Scholar 

  42. Rosen MR, Gelband H, Hoffman BF: Correlation between effects of ouabain on the cardiac electrocardiogram and transmembrane potentials of isolated Purkinje fibers. Circ Res 47:65–72, 1973.

    CAS  Google Scholar 

  43. Karagueuzian HS, Katzung BG: Relative inotropic and arrhythmogenic effects of five cardiac steriods in ventricular myocardium: oscillatory afterpotentials and the role of endogenous catecholamines. J Pharmacol Exp Ther 218: 348–356, 1981.

    PubMed  CAS  Google Scholar 

  44. Davis LD: Effect of changes in cycle length on diastolic depolarization produced by ouabain in canine Purkinje fibers. Circ Res 32:206–214, 1973.

    PubMed  CAS  Google Scholar 

  45. Ferrier GR, Saunders JH, Mendez C: A cellular mechanism for the generation of ventricular arrhythmias by acetylstrophanthidin. Circ Res 32:600–609, 1973.

    PubMed  CAS  Google Scholar 

  46. Rosen MR, Gelband H, Merker C, Hoffman BF: Mechanisms of digitalis toxicity: effects of ouabain on phase 4 of canine Purkinje fiber transmembrane potentials. Circ Res 47:681–689, 1973.

    CAS  Google Scholar 

  47. Rosen MR, Danilo P Jr: Digitalis-induced delayed afterdepolarizations. In: Zipes DP, Bailey JC, Elharrar V (eds) The Slow Inward Current and Cardiac Arrhythmias. Martinus Nijhoff, The Hague, 1980, pp 417–435.

    Google Scholar 

  48. Bassingthwaighte JB, Fry CH, McGuigan JAS: Relationship between internal calcium and outward current in mammalian ventricular muscle: a mechanism for the control of the action potential duration? J Physiol 262:15–37, 1976.

    PubMed  CAS  Google Scholar 

  49. Baumgarten C, Isenberg G: Depletion and accumulation of potassium in the extracellular clefts of cardiac Purkinje fibers during voltage clamp hyperpolarization and depolarization. Pflugers Arch 368:19–31, 1977.

    PubMed  CAS  Google Scholar 

  50. Attwell D, Eisner D, Cohen I: Voltage clamp and tracer flux data: effects of a restricted extra-cellular space. Q Rev Biophys 12:213–261, 1979.

    PubMed  CAS  Google Scholar 

  51. Kunze DL: Rate-dependent changes in extracellular potassium in the rabbit atrium. Circ Res 41:122–127, 1977.

    PubMed  CAS  Google Scholar 

  52. Kline RP, Morad M: Potassium efflux in heart muscle during activity: extracellular accumulation and its implications. J Physiol 280:537–558, 1978.

    PubMed  CAS  Google Scholar 

  53. Tsien RW, Kass RS, Weingart R: Cellular and subcellular mechanisms of cardiac pacemaker oscillations. J Exp Biol 81:205–215, 1979.

    PubMed  CAS  Google Scholar 

  54. Lederer WJ, Tsien RW: Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibers. J Physiol 263:73–100, 1976.

    PubMed  CAS  Google Scholar 

  55. Kass RS, Lederer WJ, Tsien RW, Weingart R: Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibers. J Physiol 281:187–208, 1978.

    PubMed  CAS  Google Scholar 

  56. De Mello WC: Effect of intracellular injection of calcium and strontium on cell communication in heart. J Physiol 250:231–245, 1975.

    PubMed  Google Scholar 

  57. Weingart R: The actions of ouabain on intracellular coupling and conduction velocity in mammalian ventricular muscle. J Physiol 264:341–365, 1977.

    PubMed  CAS  Google Scholar 

  58. Schwartz A: Is the cell membrane Na+, K+-ATPase enzyme system the pharmacological receptor for digitalis? Circ Res 39:2–7, 1976.

    CAS  Google Scholar 

  59. Norgaard A, Kjeldsen K, Clausen T: Potassium depletion decreases the number of 3H-ouabain binding sites and the active Na-K transport in skeletal muscle. Nature 293:739–741, 1981.

    PubMed  CAS  Google Scholar 

  60. Brown RH, Cohen I, Noble D: The interactions of protons, calcium and potassium ions on cardiac Purkinje fibers. J Physiol 282:345–352, 1978.

    PubMed  CAS  Google Scholar 

  61. Bonke FIM, Steinbeck G, Allessie MA, MacKaay AJC, Slenter VAJ: The electrophysiological effects of cardiac glycosides on the isolated sinus node of the rabbit. In: Paes de Carvalho A, Hoffman BF, Lieberman M (eds) Symposium on Normal and Abnormal Conduction in the Heart Beat. Futura Publ, New York, 1982.

    Google Scholar 

  62. Steinbeck G, Bonke FIM, Allessie MA, Lammers WJEP: The effect of ouabain on the isolated sinus node preparation of the rabbit studied with microelectrodes. Circ Res 46:406–414, 1982.

    Google Scholar 

  63. Hogan PM, Davis LD: Evidence for specialized fibers in the canine right atrium. Circ Res 23:387–396, 1968.

    PubMed  CAS  Google Scholar 

  64. Hashimoto K, Moe GK: Transient depolarizations induced by acetylstrophanthidin in specialized tissues of dog atrium and ventricle. Circ Res 32:618–624, 1973.

    PubMed  CAS  Google Scholar 

  65. Ferrier GR: The effects of tension and acetylstrophanthidin-induced transient depolarizations and aftercontractions in canine myocardial and Purkinje tissues. Circ Res 38:156–162, 1976.

    PubMed  CAS  Google Scholar 

  66. Wit AL: Personal communication.

    Google Scholar 

  67. Wit AL, Cranefield PF, Gadsby DC: Electrogenic sodium extrusion can stop triggered activity in the canine coronary sinus. Circ Res 49:1029–1042, 1981.

    PubMed  CAS  Google Scholar 

  68. Gillis RA, Quest JA: The role of the nervous system in the cardiovascular effects of digitalis. Pharmacol Rev 31:19–97, 1980.

    Google Scholar 

  69. Rosen MR: Interactions of digitalis with the autonomic nervous system and their relationship to cardiac arrhythmias. In: Abboud F, Fozzard H, Gilmore J, Reis D (eds) Disturbances in Neurogenic Control of the Circulation. Am Physiol Soc, Bethesda, 1981, pp 251–263.

    Google Scholar 

  70. Cook LS, Doherty JE, Straub KD, Nash CB, Caldwell RW: Digoxin uptake into peripheral autonomic cardiac nerves: possible mechanism of digitalis-induced antiar- rhythmic and toxic electrophysiologic actions. Am Heart J 102:58–62, 1981.

    PubMed  CAS  Google Scholar 

  71. Pace DG, Gillis RA: Neuroexcitatory effects of digoxin in the cat. J Pharmacol Exp Ther 199:583–600, 1976.

    PubMed  CAS  Google Scholar 

  72. Saum RW, Brown AM, Tuley FH: An electrogenic sodium pump and baroceptor function in normotensive and spontaneously hypertensive rats. Circ Res 39:497–505, 1976.

    PubMed  CAS  Google Scholar 

  73. Ayachi S, Brown AM: Hypotensive effects of cardiac glycosides in spontaneously hypertensive rats. J Pharmacol Exp Ther 213:520–524, 1980.

    PubMed  CAS  Google Scholar 

  74. Chai CY, Wang HH, Hoffman BF, Wang SC: Mechanisms of bradycardia induced by digitalis substances. Am J Physiol 212:26–34, 1967.

    PubMed  CAS  Google Scholar 

  75. Ten Eick RE, Hoffman BF: The effect of digitalis on the excitability of autonomic nerves. J Pharmacol Exp Ther 169:95–108, 1969.

    PubMed  Google Scholar 

  76. Toda N, West TC: the action of ouabain on the function of the atrioventricular node in rabbits. J Pharmacol Exp Ther 169:287–297, 1969.

    PubMed  CAS  Google Scholar 

  77. Horwitz LD, Atkins JM, Saito M: Effects of digitalis on left ventricular function in exercising dogs. Circ Res 41: 744–749, 1977.

    PubMed  CAS  Google Scholar 

  78. DiFrancesco D, Noma A, Trautwein W: Separation of current induced by potassium accumulation from acetylcholine-induced relaxation current in the rabbit S-A node. Pflugers Arch 387:83–90, 1980.

    PubMed  CAS  Google Scholar 

  79. Paes de Carvalho A, Hoffman BF, de Paula Carvalho M: Two components of the cardiac action potential: 1. Voltage time course and the effect of acetylcholine on atrial and nodal cells of the rabbit heart. J Gen Physiol 54:607–635, 1969.

    Google Scholar 

  80. Woods WT, Urthaler F, James TN: Electrical activity in canine sinus node cells during arrest produced by acetylcholine. J Moll Cell Cardiol 13:349–357, 1981.

    CAS  Google Scholar 

  81. Hariman RJ, Hoffman BF: Effects of ouabain and vagal stimulation on sinus nodal function in conscious dogs. Circ Res 51:760–768, 1982.

    PubMed  CAS  Google Scholar 

  82. Prokopczuk A, Lewartowski B, Czarnecka M: On the cellular mechanism of the inotropic action of acetylcholine on isolated rabbit and dog atria. Pflugers Arch 399:305–316, 1973.

    Google Scholar 

  83. Hoffman BF, Paes de Carvalho A, deMello WC, Cranefield PF: Electrical activity on single fibers on the atrioventricular node. Circ Res 7:11–18, 1959.

    PubMed  CAS  Google Scholar 

  84. Cranefield PF, Hoffman BF, Paes de Carvalho A: Effects of acetylcholine on single fibers of the atrioventricular node. Circ Res 7:19–23, 1959.

    PubMed  CAS  Google Scholar 

  85. Mendez C, Aceves J, Mendez R: Inhibition of adrenergic cardiac acceleration by cardiac glycosides. J Pharmacol Exp Ther 131:191–198, 1961.

    PubMed  CAS  Google Scholar 

  86. Nadeau RA, James TN: Antagonistic effects on the sinus node of acetyl strophanthidin and adrenergic stimulation. Circ Res 13:388–391, 1963.

    PubMed  CAS  Google Scholar 

  87. Tse WW, Han J: Interaction of epinephrine and ouabain on automaticity of canine Purkinje fibers. Circ Res 34: 777–782, 1973.

    Google Scholar 

  88. Erlij D, Mendez R: The modification of digitalis intoxication by excluding adrenergic influences on the heart. J Pharmacol Exp Ther 144:97–103, 1964.

    PubMed  CAS  Google Scholar 

  89. Ten Eick RE, Hoffman BF: Chronotropic effect of cardiac glycosides in cats, dogs and rabbits. Circ Res 25:365–378, 1969.

    PubMed  Google Scholar 

  90. Berti F, Shore PA: A kinetic analysis of drugs that inhibit the adrenergic neuronal membrane amine pump. Biochem Pharmacol 16:2091–2096, 1967.

    PubMed  CAS  Google Scholar 

  91. McLain PL: Effects of cardiac glycosides on spontaneous efferent activity in vagus and sympathetic nerves of cats. Int J Neuropharmacol 8:379–387, 1969.

    PubMed  CAS  Google Scholar 

  92. Somberg JC, Risler T, Smith TW: Neural factors in digitalis toxicity: protective effect of C-I spinal cord transection. Am J Physiol 235:H531-H536, 1978.

    PubMed  CAS  Google Scholar 

  93. Mudge GH, Lloyd BL, Greenblatt DJ, Smith TW: Inotropic and toxic effects of a polar cardiac glycoside derivative in the dog. Circ Res 43:847–854, 1978.

    PubMed  CAS  Google Scholar 

  94. Thames MD: Acetylstrophanthidin-induced reflex inhibition of canine renal sympathetic nerve activity mediated by cardiac receptors with vagal afferents. Circ Res 44:8–15, 1979.

    PubMed  CAS  Google Scholar 

  95. Mendez C, Mendez R: The action of cardiac glycosides on the excitability and conduction velocity of the mammalian atrium. J Pharmacol Exp Ther 121:402–413, 1957.

    PubMed  CAS  Google Scholar 

  96. Trautwein W: Generation and conduction of impulses in the heart as affected by drugs. Pharmacol Rev 15:277–332, 1963.

    PubMed  CAS  Google Scholar 

  97. Hoffman BF, Singer DH: Effects of digitalis on electrical activity of cardiac fibers. Prog Cardiovasc Dis 7:226–260, 1964.

    CAS  Google Scholar 

  98. Dhingra RC, Amat-y-Leon F, Wyndham C, Wu D, Denes P, Rosen K: The electrophysiological effects of ouabain on sinus node and atrium in man. J Clin Invest 56:555–562, 1975.

    PubMed  CAS  Google Scholar 

  99. Moe GK, Mendez R: The action of several cardiac glycosides on conduction velocity and ventricular excitability in the dog heart. Circulation 4:729–734, 1951.

    PubMed  CAS  Google Scholar 

  100. Swain HH, Weidner CL: A study of substances which alter intraventricular conduction in isolated dog heart. J Pharmacol Exp Ther 120:137–146, 1957.

    PubMed  CAS  Google Scholar 

  101. Gomes JAC, Dhatt MS, Akhtar M, Carambas CR, Rubenson DS, Damato A: Effects of digitalis on ventricular myocardial and His-Purkinje refractoriness and reentry in man. Am J Cardiol 42:931–939, 1978.

    PubMed  CAS  Google Scholar 

  102. Goodman DJ, Rossen RM, Cannom DS, Rider AK, Harrison DC: Effects of digoxin on atrioventricular conduction. Studies in patients with and without cardiac autonomic innervation. Circulation 51:251–256, 1975.

    PubMed  CAS  Google Scholar 

  103. Wellens HJ, Durrer D: Effect of digitalis on atrioventricular conduction and circus movement tachycardias in patients with Wolff-Parkinson-White syndrome. Circulation 47:1229–1233, 1973.

    PubMed  CAS  Google Scholar 

  104. Sellers TD Jr, Bashore TM, Gallagher JJ: Digitalis in the preexcitation syndrome: analysis during atrial fibrillation. Circulation 56:260–270, 1977.

    PubMed  Google Scholar 

  105. Kosowsky BD, Haft JI, Stein E, Damato AN: The effects of digitalis on atrioventricular conduction in man. Am Heart J 75:736–742, 1968.

    PubMed  CAS  Google Scholar 

  106. Paulay KL, Damato AN: Effect of digoxin on sinus nodal reentry in the dog. Am J Cardiol 35:370–375, 1975.

    PubMed  CAS  Google Scholar 

  107. Zakauddin V, Miller RR, McMillin D, Mason DT: Effects of digitalis on sinus nodal function in patients with sick sinus syndrome. Am J Cardiol 41:318–375, 1978.

    Google Scholar 

  108. Reiffel JA, Bigger JT Jr, Cramer M: The effects of digoxin on sinus node function before and after vagal blockade in patients with sinus node dysfunction: a clue to the mechanisms of digitalis action on the sinus node. Am J Cardiol 43:983–989, 1970.

    Google Scholar 

  109. Margolis JR, Strauss HC, Miller HC, Gilbert M, Wallace AG: Digitalis and the sick sinus syndrome: clinical and electrophysiologic documentation of a severe toxic effect on sinus node function. Circulation 52:162–169, 1975.

    PubMed  CAS  Google Scholar 

  110. Garan H, Powers ER, Ruskin JN, Powell WJ Jr: Neural effect of digitalis glycosides on gracilis vascular resistance in hypotension. Am J Physiol 238:H729-H739, 1980.

    PubMed  CAS  Google Scholar 

  111. Ayachi S, Brown AM: Hypotensive effects of cardiac glycosides in spontaneously hypertensive rats. J Pharmacol Exp Ther 213:520–524, 1980.

    PubMed  CAS  Google Scholar 

  112. Toda N: Mechanisms of ouabain-induced arterial muscle contraction. Am J Physiol 239:H199-H205, 1980.

    PubMed  CAS  Google Scholar 

  113. Berlardinelli L, Harder D, Sperelakis N, Rubio R, Berne RM: Cardiac glycoside stimulation of inward Ca++ current in vascular smooth muscle of canine coronary artery. J Pharmacol Exp Ther 209:62–66, 1979.

    Google Scholar 

  114. Bing RJ, Maraist FM, Dammann JF, Draper A, Heimbecker R, Daley R, Gerard R, Calazel P: Effect of strophanthus on coronary blood flow and cardiac oxygen consumption of normal and failing human hearts. Circulation 2:513–516, 1950.

    PubMed  CAS  Google Scholar 

  115. Vatner JF, Haig BW, Manders T, Murray PA: Effect of a cardiac glycoside on regional function, blood flow and electrograms in conscious dogs with myocardial ischemia. Circ Res 43:413–423, 1978.

    PubMed  CAS  Google Scholar 

  116. McRitchie RJ, Vatner SF: The role of the arterial baroceptors in mediating cardiovascular responses to cardiac glycosides in conscious dogs. Circ Res 38:321–326, 1976.

    PubMed  CAS  Google Scholar 

  117. Vatner SF, Braunwald E: Effects of chronic heart failure on the inotropic response of the right ventricle of the conscious dog to a cardiac glycoside and to tachycardia. Circulation 50:728–734, 1974.

    PubMed  CAS  Google Scholar 

  118. Mason DT, Braunwald E: Studies on digitalis. X. Effects of ouabain on forearm vascular resistance and venous tone in normal subjects and in patients in heart failure. J Clin Invest 43:532–543, 1964.

    PubMed  CAS  Google Scholar 

  119. Williams MH, Zohman LR, Ratner AC: Hemodynamic effects of cardiac glycosides on normal human subjects during rest and exercise. J Appl Physiol 13:417–421, 1958.

    PubMed  CAS  Google Scholar 

  120. Smith TW, Haber E: Medical progress: digitalis. N Engl J Med 289:945–952, 1010–1015, 1063–1072, 1125–1129, 1973.

    PubMed  CAS  Google Scholar 

  121. Braunwald E, Bloodwell RD, Goldberg LI, Morrow AG: Studies on Digitalis. IV. Observations in man on the effects of digitalis preparations on the contractility of the nonfailing heart and on total vascular response. J Clin Invest 40:52–59, 1959.

    Google Scholar 

  122. Dresdale PT, Yuceoglu YZ, Michton RJ, Schultz M, Lunger M: Effects of lanatoside C on cardiovascular hemodynamics - acute digitalizing doses in subject with normal hearts and with heart disease without failure. Am J Cardiol 4:88–99, 1959.

    PubMed  CAS  Google Scholar 

  123. Selzer A, Hultgren HN, Ebnother CL, Bradley HW, Stone AO: Effects of digoxin on the circulation in normal man. Br Heart J 21:335–342, 1959.

    PubMed  CAS  Google Scholar 

  124. Lindenbaum J, Butler VP, Murphy JE, Cresswell RM: Correlation of digoxin-tablet dissolution rate with biological availability. Lancet 1:1215–1217, 1973.

    PubMed  CAS  Google Scholar 

  125. Lindenbaum J, Mellow MH, Blackstone MO, Butler VP Jr: Variability in biological availability of digoxin from four preparations. N Engl J Med 285:1344–1347, 1971.

    PubMed  CAS  Google Scholar 

  126. Wagner JG, Christensen M, Sakmar E, Blair D, Yates JD, Willis PW III, Sedman AH, Stall RG: Equivalence lack in digoxin plasma levels. J Am Med Assoc 224:199–204, 1973.

    CAS  Google Scholar 

  127. Harter JG, Skelly JP, Steers AW: Digoxin - the regulatory viewpoint. Circulation 49:395–398, 1974.

    PubMed  CAS  Google Scholar 

  128. Lindenbaum J, Rund DG, Butler VP, Tse-Eng D, Saha JR: Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N Engl J Med 305:789–794, 1981.

    PubMed  CAS  Google Scholar 

  129. Frazer G, Binnion P: 3H-digoxin distribution in the nervous system in ventricular tachycardia. J Cardiovasc Pharmacol 3:1296–1305, 1981.

    PubMed  CAS  Google Scholar 

  130. Cogan JJ, Humphreys MH, Carlson J, Benowitz NL, Rapaport E: Acute vasodilator therapy increases renal clearance of digoxin in patients with congestive heart failure. Circulation 64:973–976, 1981.

    PubMed  CAS  Google Scholar 

  131. Risler T, Somberg JC, Blute RD Jr, Smith TW: The effect of altered renal perfusion pressure on clearance of digoxin. Circulation 61:521–525, 1980.

    PubMed  CAS  Google Scholar 

  132. Leahey EB Jr, Reiffel JA, Drusin RE, Heissenbuttel RH, Lovejoy WP, Bigger JT Jr: Interaction between digoxin, quinidine. J Am Med Assoc 240:533–534, 1978.

    Google Scholar 

  133. Ejvinsson G: Effect of quinidine on plasma concentrations of digoxin. Br Med J 1:279–280, 1978.

    PubMed  CAS  Google Scholar 

  134. Doering W, Konig E: Ansteig der digoxin Konzentration im Serum unter chinidin Medikation. Med Clin 73:1085–1088, 1978.

    CAS  Google Scholar 

  135. Doering W: Digoxin-quinidine interaction. N Engl J Med 301:400–405, 1979.

    PubMed  CAS  Google Scholar 

  136. Leahey EB Jr, Reiffel JA, Giardina EGV, Bigger JT Jr: The effect of quinidine and other oral antiarrhythmic drugs on serum digoxin. A prospective study. Ann Intern Med 92: 605–608, 1980.

    PubMed  Google Scholar 

  137. Mungall DR, Robichaux RP, Perry W, Scott JW, Robinson A, Burelle T, Hurst D: Effects of quinidine on serum digoxin concentration. Ann Intern Med 93:689–693, 1980.

    PubMed  CAS  Google Scholar 

  138. Pedersen KE, Hastrop J, Hvidt S: The effect of quinidine on digoxin kinetics in cardiac patients. Acta Med Scand 207:291–295, 1980.

    PubMed  CAS  Google Scholar 

  139. Dahlqvist R, Ejvinsson G, Schenck-Gustafsson K: Effect of quinidine on plasma concentration and renal clearance of digoxin. A clinically important drug interaction. Br J Clin Pharmacol 9:412–418, 1980.

    Google Scholar 

  140. Leahey EB Jr, Bigger JT Jr, Bulter VP Jr, Reifer JA, O’Connell GC, Scaffidi LE, Rottman JN: Quinidine-digoxin interaction. Time course and pharmacokinetics. Am J Cardiol 48:1141–1146, 1981.

    PubMed  CAS  Google Scholar 

  141. Kum DH, Akera T, Brody TM: Effects of quinidine on the cardiac-glycoside sensitivity of guinea-pig and rat heart. J Pharmacol Exp Ther 217:559–565, 1981.

    Google Scholar 

  142. Horowitz JD, Barry WH, Smith TW: Lack of interaction between digoxin and quinidine in cultured heart cells. J Pharmacol Exp Ther 220:488–493, 1982.

    PubMed  CAS  Google Scholar 

  143. Hirsh PD, Weiner HJ, North RL: Further insights into digoxin-quinidine interaction: lack of correlation between serum digoxin concentration and inotropic state of the heart. Am J Cardiol 46:863–867, 1981.

    Google Scholar 

  144. Steiness E, Waldorff S, Hansen PB, Kjaergard H, Buch J, Edgblad H: Reduction of digoxin-induced inotropism during quinidine administration. Clin Pharmacol Ther 27: 791–795, 1980.

    PubMed  CAS  Google Scholar 

  145. Fenster PE, Powell JR, Graves PE, Conrad KA, Hager WD, Goldman S, Marcus FI: Digitoxin-quinidine interaction: pharmacokinetic evaluation. Ann Intern Med 93: 698–701, 1980.

    PubMed  CAS  Google Scholar 

  146. Garty M, Sood P, Rollins DE: Digitoxin elimination reduced during quinidine therapy. Ann Intern Med 94:35–37, 1981.

    PubMed  CAS  Google Scholar 

  147. Ochs HR, Pabst J, Greenblatt DJ, Dengler HJ: Noninteraction of digitoxin and quinidine. N Engl J Med 303:672–674, 1980.

    PubMed  CAS  Google Scholar 

  148. Peters U, Risler T, Grabensee B, Falkenstein U, Kroukou J: Interaktion von chinidin und digitoxin beim Menschen. Dtsch Med Wochenschr 105:438–442, 1980.

    PubMed  CAS  Google Scholar 

  149. Storstein L, von der Lippe A, Amlie J, Storstein O: Is there an interaction between digitoxin and quinidine? Circulation 59–60 (Suppl II):II-230, 1979.

    Google Scholar 

  150. Keller F, Kreutz G: Chinidin Interaktion mit digitoxin. Dtsch Med Wochenschr 105:701–702, 1980.

    PubMed  CAS  Google Scholar 

  151. Moysey JO, Jaggarao NSV, Grundy EN, Chamberlain DA: Amiodarone increases plasma digoxin concentrations. Br Med J 282:272–273, 1981.

    CAS  Google Scholar 

  152. Garcia-Barreto D, Groning E, Gonzalez-Gomez A, Perez A, Hernadez-Canero A, Toruncha A: Enhancement of the antiarrhythmic aciton of disopyramide by digoxin. J Cardiovasc Pharmacol 3:1236–1242, 1981.

    PubMed  CAS  Google Scholar 

  153. Lang R, Klein HO, Weiss E, Libhaber C, Kaplinsky E: Effect of verapamil on blood level and renal clearance of digoxin. Circulation 62 (Suppl III):III-83, 1980.

    Google Scholar 

  154. Pedersen KE, Doph-Pedersen A, Hvidt S, Klitgaard NA, Nielsen-Kudsk F: Digoxin-verapamil interaction. Clin Pharmacol Ther 30:311–316, 1981.

    PubMed  CAS  Google Scholar 

  155. Doering W: Quinidine-digoxin interaction (pharmacokinetics underlying mechanism and clinical implications). N Engl J Med 301:400–404, 1979.

    PubMed  CAS  Google Scholar 

  156. Belz GG, Aust PE, Munkes R: Digoxin plasma concentrations and nifedipine. Lancet 1:844–845, 1981.

    PubMed  CAS  Google Scholar 

  157. Rosen MR, Fisch C, Hoffman BF, Danilo P, Lovelace DE, Knoebel SB: Can accelerated atrioventricular junctional escape rhythms be explained by delayed afterdepolarizations? Am J Cardiol 45:1272–1284, 1980.

    PubMed  CAS  Google Scholar 

  158. Irons GV Jr, Orgain ES: Digitalis-induced arrhythmias and their management. Prog Cardiovasc Dis 8:539–568, 1966.

    PubMed  Google Scholar 

  159. Rosen MR, Hordof AJ, Hodess A, Verosky M, Vulliemoz L: Ouabain induced changes in electrophysiologic properties of neonatal, young and adult canine cardiac Purkinje fibers. J Pharmacol Exp Ther 194:255–263, 1973.

    Google Scholar 

  160. Somberg JC, Kuhlman JE, Smith TW: Localization of neurally mediated coronary vasoconstrictor properties of digitalis in the cat. Circ Res 49:226–233, 1981.

    PubMed  CAS  Google Scholar 

  161. Chai CY, Hsu PL, Wang SC: Central locus of emetic action of digitalis substances in cats. Neuropharmacology 12: 1187–1193, 1973.

    PubMed  CAS  Google Scholar 

  162. Binnion PF, Frazer G: [3H] digoxin in the optic tract in digoxin intoxication. J Cardiovasc Pharmacol 2:699–706, 1980.

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Martinus Nijhoff Publishers, Boston, The Hague, Dordrecht, Lancaster

About this chapter

Cite this chapter

Hoffman, B.F. (1983). The pharmacology of cardiac glycosides. In: Rosen, M.R., Hoffman, B.F. (eds) Cardiac therapy. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3855-0_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-3855-0_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-3857-4

  • Online ISBN: 978-1-4613-3855-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics