Equis ISSN 2398-2977

Toxicity: digoxin

Synonym(s): Cardenolide

Contributor(s): Steven Gallego, Birgit Puschner, Nicola Bates

Introduction

  • Cause: digoxin therapy or ingestion of foxglove.
  • Signs: general weakness, exercise intolerance, inappetence, tremors, convulsions, tachypnea, cardiac arrhythmias, recumbency.
  • Diagnosis: cardiac auscultation, ECG, serum digoxin detection, foxglove contaminated feed or pasture.
  • Treatment: removal of contaminated feed. Cessation of digitalis therapy. Phenytoin intervention. Supportive care.
  • Prognosis: guarded.

Pathogenesis

Etiology

  • Horses are infrequently poisoned with plants containing cardiac glycosides Poisonous plants: overview, due to the unpalatable nature of the plants, but may ingest the plant either fresh or dried in hay.
  • Some animals have been reported to actively seek the plants to graze on them.
  • Foxgloves remain toxic when dried Foxglove (Digitalis pupurea).
  • Iatrogenic - digoxin is considered a positive inotrope and utilized as an economical therapy (digitalization) for certain tachyarrhythmias (supraventricular tachyarrhythmia) or congestive heart failures (CHF) resulting from ineffective myocardial contraction or systolic dysfunction. Toxicities have occurred in horses receiving what are considered therapeutic levels.

Predisposing factors

General

  • Poor pasture/feed management, and lack of or inability to access other forage.
  • Poor CHF digoxin monitoring.

Specific

  • Easy public access to pasture or feed areas.
  • Unsolicited gardening refuse disposal.
  • Poor regular pasture surveillance or elimination of noxious plants.
  • Failure to monitor CHF patient serum digoxin levels as well as not recognizing tremors and drowsiness as sign of overdose.

Pathophysiology

  • Positive inotrope - strengthens myocardial contraction:
    • Digoxin blocks the cell’s Na/K ion exchange creating increased intracellular Na, which in turn creates increased Ca levels contributing to greater myocyte contractility.
  • Negative chronotrope - prolongs diastolic phase:
    • Increased parasympathetic or vagal tone, decreased sympathetic tone.
    • Slows AV bundle impulse conduction signal to ventricles, increases membrane action potential threshold and thus slows sinoatrial node impulse production.
  • Cardiac glycosides also have irritant effects on the gastrointestinal tract.

Timecourse

  • Clinical signs usually occur within 6 h of ingestion.
  • When poisoning occurs, the clinical signs may be severe and dramatic.
  • Death may occur rapidly or up to 36-48 h after ingestion.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed Papers

  • Recent references PubMed and VetMedResource.
  • Pao-Franco A, Hammond T N, Weatherton L K, DeClementi C & Forney S D (2017) Successful use of digoxin-specific immune Fab in the treatment of severe Nerium oleander toxicosis in a dog. J Vet Emerg Crit Care (San Antonio) 27 (5), 596-604 PubMed.
  • Sleeper M M (2017) Equine cardiovascular therapeutics. Vet Clin Equine 33, 163-179 PubMed.
  • Renier A C, Kass P H, Magdesian K G et al (2013) Oleander toxicosis in equids: 30 cases (1995-2010). JAVMA 242 (4), 540-9 PubMed.
  • Varga A & Puschner B (2012) Retrospective study of cattle poisonings in California: recognition, diagnosis and treatment. Vet Med 3, 111-127 PubMed.
  • Wijnberg I D & Ververs F F T (2004) Phenytoin sodium as a treatment for ventricular dysrhythmia in horses. J Vet Intern Med 18, 350-353 PubMed.
  • Smith P A, Aldridge B M & Kittleson M D (2003) Oleander toxicosis in a donkey. J Vet Intern Med 17 (1), 111-4 PubMed.
  • Hughes K J, Dart A J, Hodgson D R (2002) Suspected Nerium oleander (Oleander) poisoning in a horse. Aust Vet J 80 (7), 412-5 PubMed.
  • Gwaltney-Brant S M & Rumbeiha W K (2002) Newer antidotal therapies. Vet Clin North Am Small Anim Pract 32 (2), 323-339 PubMed.
  • Wijnberg I D, van der Kolk J H & Hiddink E G (1999) Use of phenytoin to treat digitalis-induced cardiac arrhythmias in a miniature Shetland pony. Vet Rec 144, 259-261 PubMed.
  • Brumbaugh G W, Thomas W P & Enos L R (1983) A pharmacokinetic study of digoxin in the horse. J Vet Pharmacol Ther 6, 163-172 PubMed.
  • Corrigall W, Moody R R, Forbes J C (1978) Foxglove (Digitalis purpurea) poisoning in farmed red deer (Cervus elaphus). Vet Rec 102, 119-122 PubMed.

Other sources of information

  • Burrows G E & Tyrl R J (2013) Toxic Plants of North America. 2nd edn. Wiley Blackwell, USA.
  • De Clercq D, Decloedt A & van Loon G (2012) Atrial Standstill in a Horse with Cardiac Glycoside Intoxication. In: Proceedings of the European Veterinary Conference, Voorjaarsdagen Amsterdam, Netherlands. pp 302.
  • Plumb D C (2005) Plumb’s Veterinary Drug Handbook. 5th edn. Donald C. Blackwell Publishing, USA.
  • Durie I, van Loon G, De Clercq D & Deprez P (2008) Nerium Oleander Intoxication in hHrses; 3 Cases [abstract]. In: Proceedings of the 47th British Equine Veterinary Association Congress, UK.
  • Frohne D, Pfänder H J (2004) A Colour Atlas of Poisonous Plants: A Handbook for Pharmacists, Doctors, Toxicologists, and Biologists. Timber Press, UK.
  • Knight A P & Walter R G (2001) A Guide to Plant Poisonings of Animals in North America. Teton NewMedia, USA.
  • Cooper M R & Johnson A W (1998) Poisonous Plants and Fungi in Britain. 2nd edn. The Stationery Office, UK.
  • Rezakhani A, Maham M (1994) Cardiac Manifestations of Oleander Poisoning in Cattle and Donkeys. In: Plant-associated Toxins: Agricultural, Phytochemical and Ecological Aspects. Eds: Colegate SM, Dorling PR, Allen JG, Huxtable CR, Panter KE. CAB International, UK. pp 534-537.
  • Robinson N E (1983) Current Therapy in Equine Medicine. W B Saunders Co, USA.

Organisation(s)

  • ASPCA Animal Poison Control Center. Tel: +1 (888) 426-4435. Website: www.aspca.org.
  • Department of Animal Science - Plants Poisonous to Livestock (database of poisonous plants). Cornell University. Website: www.ansci.cornell.edu.
  • Veterinary Poisons Information Service (VPIS). Tel: + 44 (0) 2073 055 055. Website: www.vpisglobal.com.


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