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Digitalis Glycosides

  • Bruno Mégarbane
Reference work entry

Abstract

The medical use of cardiac glycosides began in 1785 with the publication of Withering’s monograph on the therapeutic efficacy and toxicity of the leaves of the common foxglove plant,. Various glycosides including digitoxin and ouabain were then extracted from plants, and digitalis glycosides have been widely prescribed for more than 230 years.

Keywords

Digitalis glycosides Cardiac glycosides Digitalis purpurea Digitoxin Ouabain Digitalis poisoning Oleander Convallaria majalis Lily of the valley Convallarin Convallamarin Convallatoxin Bufo toad Magnesium Anti-digoxin-specific Fab fragments 

Notes

Acknowledgments

The author would like to thank Prof. Frédéric Lapostolle who contributed to the first version of this chapter.

References

  1. 1.
    Ziff OJ, Kotecha D. Digoxin: the good and the bad. Trends Cardiovasc Med. 2016;pii: S1050-1738(16)30006-8.Google Scholar
  2. 2.
    The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336:525–33.CrossRefGoogle Scholar
  3. 3.
    Ahmed A, Rich MW, Fleg JL, et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006;114:397–403.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Goldberger ZD, Alexander GC. Digitalis use in contemporary clinical practice: refitting the foxglove. J Am Med Assoc Intern Med. 2014;174:151–4.Google Scholar
  5. 5.
    Smith TW, Haber E, Yeatman L, Butler Jr VP. Reversal of advanced digoxin intoxication with Fab fragments of digoxin-specific antibodies. N Engl J Med. 1976;294:797–800.CrossRefPubMedGoogle Scholar
  6. 6.
    Roberts DM, Gallapatthy G, Dunuwille A, Chan BS. Pharmacological treatment of cardiac glycoside poisoning. Br J Clin Pharmacol. 2016;81:488–95.CrossRefPubMedGoogle Scholar
  7. 7.
    Smith TW. Digitalis: mechanisms of action and clinical use. N Engl J Med. 1988;318:358–65.CrossRefPubMedGoogle Scholar
  8. 8.
    Wasserstrom JA, Aistrup GL. Digitalis: new actions for an old drug. Am J Physiol Heart Circ Physiol. 2005;289:H1781–93.CrossRefPubMedGoogle Scholar
  9. 9.
    Gheorghiade M, St Clair J, St Clair C, Beller GA. Hemodynamic effects of intravenous digoxin in patients with severe heart failure initially treated with diuretics and vasodilators. J Am Coll Cardiol. 1987;9:849–57.CrossRefPubMedGoogle Scholar
  10. 10.
    Wofford JL, Ettinger WH. Risk factors and manifestations of digoxin toxicity in the elderly. Am J Emerg Med. 1991;9(2 Suppl 1):11–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Hauptman PJ, Blume SW, Lewis EF, Ward S. Digoxin toxicity and use of digoxin immune Fab: insights from a national hospital database. JACC Heart Fail. 2016;4:357–64.CrossRefPubMedGoogle Scholar
  12. 12.
    Hickey AR, Wenger TL, Carpenter VP, Tilson HH, Hlatky MA, Furberg CD, et al. Digoxin immune Fab therapy in the management of digitalis intoxication: safety and efficacy results of an observational surveillance study. J Am Coll Cardiol. 1991;17:590–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Nordt SP, Clark RF, Machado C, Cantrell FL. Assessment of digoxin-specific fab fragment dosages in digoxin poisoning. Am J Ther. 2016;23:e63–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Chhabra N, Valento M, Bryant SM, Aks SE. Digoxin-specific antibody fragment dosing: a case series. Am J Ther. 2016 (in press).Google Scholar
  15. 15.
    Antman EM, Wenger TL, Butler Jr VP, Haber E, Smith TW. Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: final report of a multicenter study. Circulation. 1990;81:1744–52.CrossRefPubMedGoogle Scholar
  16. 16.
    Chan BS, Isbister GK, O’Leary M, Chiew A, Buckley NA. Efficacy and effectiveness of anti-digoxin antibodies in chronic digoxin poisonings from the DORA study (ATOM-1). Clin Toxicol (Phila). 2016;54:488–94.CrossRefGoogle Scholar
  17. 17.
    Lapostolle F, Borron SW, Verdier C, Arnaud F, Couvreur J, Mégarbane B, et al. Assessment of digoxin antibody use in patients with elevated serum digoxin following chronic or acute exposure. Intensive Care Med. 2008;34:1448–53.CrossRefPubMedGoogle Scholar
  18. 18.
    Yang EH, Shah S, Criley JM. Digitalis toxicity: a fading but crucial complication to recognize. Am J Med. 2012;125:337–43.CrossRefPubMedGoogle Scholar
  19. 19.
    Kanji S, MacLean RD. Cardiac glycoside toxicity: more than 200 years and counting. Crit Care Clin. 2012;28:527–35.CrossRefPubMedGoogle Scholar
  20. 20.
    Dally S, Alperovitch A, Lagier G, Bismuth C, Fournier E. Prognostic factors in acute digitalis poisoning. Nouv Presse Med. 1981;10:2257–60.PubMedGoogle Scholar
  21. 21.
    Lapostolle F, Borron SW, Verdier C, Taboulet P, Guerrier G, Adnet F, et al. Digoxin-specific Fab fragments as single first-line therapy in digitalis poisoning. Crit Care Med. 2008;36:3014–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Ordog G, Benaron S, Bhasin V. Serum digoxin levels and mortality in 5100 patients. Ann Emerg Med. 1987;16:32–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Shapiro W. Correlative studies of serum digitalis levels and the arrhythmias of digitalis intoxication. Am J Cardiol. 1978;41:852–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Williamson KM, Thrasher KA, Fulton KB, LaPointe NM, Dunham GD, Cooper AA, et al. Digoxin toxicity: an evaluation in current clinical practice. Arch Intern Med. 1998;158:2444–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Lehmann HU, Witt E, Temmen L, Hochrein H. Life-threatening digitalis intoxication with and without additional diuretic treatment. Dtsch Med Wochenschr. 1978;103:1566–71.CrossRefPubMedGoogle Scholar
  26. 26.
    Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol. 1999;37:731–51.Google Scholar
  27. 27.
    Mowry JB, Burdmann EA, Anseeuw K, Ayoub P, Ghannoum M, Hoffman RS, et al. Extracorporeal treatment for digoxin poisoning: systematic review and recommendations from the EXTRIP Workgroup. Clin Toxicol (Phila). 2016;54:103–14.CrossRefGoogle Scholar
  28. 28.
    Navab F, Honey M. Self-poisoning with digoxin: successful treatment with atropine. Br Med J. 1967;3:660–1.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Mooradian A. Digitalis: an update of clinical pharmacokinetics, therapeutic monitoring techniques and treatment recommendations. Clin Pharmacokinet. 1988;15:165–79.CrossRefPubMedGoogle Scholar
  30. 30.
    Cohen L, Kitzes R. Magnesium sulfate and digitalis-toxic arrhythmias. JAMA. 1983;249:2808–10.CrossRefPubMedGoogle Scholar
  31. 31.
    French JH, Thomas RG, Siskind AP, Brodsky M, Iseri LT. Magnesium therapy in massive digoxin intoxication. Ann Emerg Med. 1984;13:562–6.CrossRefPubMedGoogle Scholar
  32. 32.
    Reisdorff EJ, Clark MR, Walters BL. Acute digitalis poisoning: the role of intravenous magnesium sulfate. J Emerg Med. 1986;4:463–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Bismuth C, Motte G, Conso F, Chauvin M, Gaultier M. Acute digitoxin intoxication treated by intracardiac pacemaker: experience in sixty-eight patients. J Toxicol Clin Toxicol. 1977;10:443–56.CrossRefGoogle Scholar
  34. 34.
    Taboulet P, Baud FJ, Bismuth C, Vicaut E. Acute digitalis intoxication – is pacing still appropriate? J Toxicol Clin Toxicol. 1993;31:261–73.CrossRefPubMedGoogle Scholar
  35. 35.
    Berkovitch M, Akilesh MR, Gerace R, Verjee Z, McGuigan M, Whyte H, et al. Acute digoxin overdose in a newborn with renal failure: use of digoxin immune Fab and peritoneal dialysis. Ther Drug Monit. 1994;16:531–3.CrossRefPubMedGoogle Scholar
  36. 36.
    Gittelman MA, Stephan M, Perry H. Acute pediatric digoxin ingestion. Pediatr Emerg Care. 1999;15:359–62.CrossRefPubMedGoogle Scholar
  37. 37.
    Kaufman J, Leikin J, Kendzierski D, Polin K. Use of digoxin Fab immune fragments in a seven-day-old infant. Pediatr Emerg Care. 1990;6:118–21.CrossRefPubMedGoogle Scholar
  38. 38.
    Schmitt K, Tulzer G, Hackel F, Sommer R, Tulzer W. Massive digitoxin intoxication treated with digoxin-specific antibodies in a child. Pediatr Cardiol. 1994;15:48–9.CrossRefPubMedGoogle Scholar
  39. 39.
    Woolf AD, Wenger T, Smith TW, Lovejoy Jr FH. The use of digoxin-specific Fab fragments for severe digitalis intoxication in children. N Engl J Med. 1992;326:1739–44.CrossRefPubMedGoogle Scholar
  40. 40.
    Mauskopf JA, Wenger TL. Cost-effectiveness analysis of the use of digoxin immune Fab (ovine) for treatment of digoxin toxicity. Am J Cardiol. 1991;68:1709–14.CrossRefPubMedGoogle Scholar
  41. 41.
    Kurowski V, Iven H, Djonlagic H. Treatment of a patient with severe digitoxin intoxication by Fab fragments of anti-digitalis antibodies. Intensive Care Med. 1992;18:439–42.CrossRefPubMedGoogle Scholar
  42. 42.
    Hess T, Stucki P, Barandun S, Scholtysik G, Riesen W. Treatment of a case of lanatoside C intoxication with digoxin-specific F(ab′)2 antibody fragments. Am Heart J. 1979;98:767–71.CrossRefPubMedGoogle Scholar
  43. 43.
    Eddleston M, Rajapakse S, Rajakanthan K, Jayalath S, Sjöström L, Santharaj W, et al. Anti-digoxin Fab fragments in cardiotoxicity induced by ingestion of yellow oleander: a randomized controlled trial. Lancet. 2000;355:967–71.CrossRefPubMedGoogle Scholar
  44. 44.
    Bandara V, Weinstein SA, White J, Eddleston M. A review of the natural history, toxinology, diagnosis and clinical management of Nerium oleander (common oleander) and Thevetia peruviana (yellow oleander) poisoning. Toxicon. 2010;56:273–81.CrossRefPubMedGoogle Scholar
  45. 45.
    Roberts DM, Buckley NA. Antidotes for acute cardenolide (cardiac glycoside) poisoning. Cochrane Database Syst Rev. 2006;4, CD005490.Google Scholar
  46. 46.
    Maillaud C, Barguil Y, Mikulski M, Cheze M, Pivert C, Deveaux M, et al. First successful curative use of digoxin-specific Fab antibody fragments in a life-threatening coconut crab (Birgus latro L.) poisoning. Toxicon. 2012;60:1013–7.CrossRefPubMedGoogle Scholar
  47. 47.
    Chan BS, Buckley NA. Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Clin Toxicol (Phila). 2014;52:824–36.CrossRefGoogle Scholar
  48. 48.
    Smolarz A, Roesch E, Lenz E, Neubert H, Abshagen P. Digoxin specific antibody (Fab) fragments in 34 cases of severe digitalis intoxication. J Toxicol Clin Toxicol. 1985;23:327–40.CrossRefPubMedGoogle Scholar
  49. 49.
    Bismuth C, Motté G, Fréjaville JP, Conso F. Hyperkalemia in massive digitalis intoxication. Prognostic value and therapeutic implications. Arch Mal Coeur Vaiss. 1973;66:1537–41.PubMedGoogle Scholar
  50. 50.
    Taboulet P, Baud FJ, Bismuth C. Clinical features and management of digitalis poisoning – rationale for immunotherapy. J Toxicol Clin Toxicol. 1993;31:247–60.CrossRefPubMedGoogle Scholar
  51. 51.
    Mégarbane B, Baud FJ. Early digoxin-specific antibody fragments for treating patients at risk of life-threatening digoxin toxicity. Clin Toxicol (Phila). 2014;52:985–6.CrossRefGoogle Scholar
  52. 52.
    Wenger TL, Butler Jr VP, Haber E, Smith TW. Treatment of 63 severely digitalis-toxic patients with digoxin-specific antibody fragments. J Am Coll Cardiol. 1985;5(5 Suppl A):118A–23.CrossRefPubMedGoogle Scholar
  53. 53.
    Ujhelyi MR, Robert S. Pharmacokinetic aspects of digoxin-specific Fab therapy in the management of digitalis toxicity. Clin Pharmacokinet. 1995;28:483–93.CrossRefPubMedGoogle Scholar
  54. 54.
    Brunner G, Zweiker R, Krejs GJ. A toxicological surprise. Lancet. 2000;356:1406.CrossRefPubMedGoogle Scholar
  55. 55.
    Portnoi V. Digitalis delirium in the elderly. J Clin Pharmacol. 1979;19:747–50.CrossRefPubMedGoogle Scholar
  56. 56.
    Renard C, Grene-Lerouge N, Beau N, Baud F, Scherrmann JM. Pharmacokinetics of digoxin-specific Fab: Effects of decreased renal function and age. Br J Clin Pharmacol. 1997;44:135–8.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Ujhelyi MR, Robert S, Cummings DM, Colucci RD, Green PJ, Sailstad J, et al. Influence of digoxin immune Fab therapy and renal dysfunction on the disposition of total and free digoxin. Ann Intern Med. 1993;119:273–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Medical and Toxicological Critical Care, Lariboisière HospitalParis-Diderot UniversityParisFrance

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