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Not to be confused with Dioxin or Digitoxin.
Digoxin structure 2.svg
Digon ball-and-stick.png
Systematic (IUPAC) name
Clinical data
Trade names Lanoxin
AHFS/Drugs.com monograph
MedlinePlus a682301
Routes Oral, Intravenous
Pharmacokinetic data
Bioavailability 60 to 80% (Oral)
Protein binding 25%
Metabolism Hepatic (16%)
Half-life 36 to 48 hours
(patients with normal renal function)
3.5 to 5 days
(patients with impaired renal function)
Excretion Renal
CAS number 20830-75-5 YesY
ATC code C01AA05
PubChem CID 2724385
DrugBank DB00390
ChemSpider 2006532 YesY
UNII 73K4184T59 YesY
KEGG D00298 YesY
Chemical data
Formula C41H64O14 
Mol. mass 780.938 g/mol
Physical data
Melt. point 249.3 °C (481 °F)
Solubility in water 0.0648 mg/mL (20 °C)
 YesY (what is this?)  (verify)

Digoxin INN (/dɨˈɒksɨn/[1]) is a purified cardiac glycoside similar to digitoxin extracted from the foxglove plant, Digitalis lanata,[2] which was discovered by William Withering. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin. Digoxin is widely used in the treatment of various heart conditions, namely atrial fibrillation, atrial flutter and sometimes heart failure that cannot be controlled by other medication.


Digoxin was discovered by physician William Withering, a graduate of the University of Edinburgh Medical School.


Medical use[edit]

Derivatives of plants of the genus Digitalis have a long history of medical use. The British physician William Withering is credited with the first published description of the use of digitalis derivatives in his 1785 book "An Account of the Foxglove and some of its Medical Uses With Practical Remarks on Dropsy and Other Diseases".[4]

Today, the most common indications for digoxin are atrial fibrillation and atrial flutter with rapid ventricular response, though beta blockers and/or calcium channel blockers are a better first choice.[5][6] High ventricular rate leads to insufficient diastolic filling time. By slowing down the conduction in the AV node and increasing its refractory period, digoxin can reduce the ventricular rate. The arrhythmia itself is not affected, but the pumping function of the heart improves owing to improved filling.


Digitalis/digoxin has recently fallen out of favor because it did not demonstrate a mortality benefit in patients with congestive heart failure; however, it did demonstrate a reduction in hospitalizations for this condition.[7] Because other therapies have shown a mortality benefit in congestive heart failure, maximizing other therapies (e.g., beta blockers) first is recommended before using digoxin.

Adverse effects[edit]

Main article: Digoxin toxicity







Patients taking digoxin should avoid taking hawthorn.[17][18]

Pharmacokinetic properties[edit]







Mechanisms of action[edit]

The main pharmacological effects of digoxin are on the heart. Extracardiac effects are responsible for some of the therapeutic and many of the adverse effects (see above). It exerts a mechanical effects as it increases myocardial contractility; however, the duration of the contractile response is just slightly increased. Overall, the heart rate is decreased, while blood pressure is increased resulting in an net increase in stroke volume, leading to increased tissue perfusion. This causes the myocardium to work more efficiently, with optimised haemodynamics and the ventricular function curve is improved.

Other electrical effects include an initial brief increase in action potential, followed by a decrease as the K+ conductance increases due to an increased intracellular amounts of Ca2+ ions. The refractory period of the atria and ventricles is decreased, while it increases in the sinoatrial and AV nodes. A less negative resting membrane potential is made, leading to increased irritability. Other, more indirect effects are cholinomimetic because of vagal stimulation, giving rise to AV nodal delay.


ECG changes seen in patient taking digoxin include increased PR interval (due to decreased AV conduction) and a decreased QT interval. Also, the T wave may be inverted and accompanied by ST depression. It may cause AV junctional rhythm and ectopic beats (bigeminy) resulting in ventricular tachycardia and fibrillation.



Mechanism of action[edit]


Digoxin is a cardiac glycoside that acts as an inotropic agent, it decreases the action of the Na+/K+ ATPase channel by binding to an allosteric site. Normally 3 X Na+ moves out of the cardiac cell and 2 X K+ moves into the cardiac cell. As a result,Na+ concentration in myocyte increases and inactivates the NCX antiporter protein, which Na+ will no longer be pumped into the myocyte. On the other hand, inactivation of NCX causes Ca2+ concentration to increase inside the cell as Ca2+ cannot be pumped out. Increase in Ca2+ concentration thus aid contraction in the heart. Digoxin also acts as a vagal agonist. Hence, its secondary effect of decreased heart rate. Toxicity is marked by Atrial Tachycardia due to ectopy and AV block due to its vagal stimulating properties.

The benefits of digoxin are an increased stroke volume, increased ejection fraction and decreased heart rate.

Society and culture[edit]


On April 25, 2008, the FDA issued a press release[21] alerting the public to a Class I recall of Digitek, a brand of digoxin produced by Mylan.[22] Some tablets had been released at double thickness and therefore double strength, causing some patients to experience digoxin toxicity. A class-action lawsuit against the Icelandic generic drug maker Actavis was announced two weeks later.[23]




A 2008 study suggested digoxin has beneficial effects not only for the heart, but also in reducing the risk of certain kinds of cancer.[24] However, comments on this study suggested that digoxin is not effective at reducing cancer risk at therapeutic concentrations of the drug,[25] so the results need further investigation.[26]

In the Turkish movie Once Upon a Time in Anatolia the prosecutor tells the doctor a story of a 'gorgeous woman' who died on the date she predicted she would die, well after delivering the baby. The doctor speculates she may have taken high doses of Dogoxin to die of heart attack. There are hints that she may have been the prosecutor's wife who committed suicide because she couldn't take his one time affair.


  1. ^ OED
  2. ^ Hollman A (1996). "Digoxin comes from Digitalis lanata". British Medical Journal 312 (7035): 912. doi:10.1136/bmj.312.7035.912. 
  4. ^ Withering, William (1785). An Account of the Foxglove and some of its Medical Uses With Practical Remarks on Dropsy and Other Diseases. 
  5. ^ Sticherling C, Oral H, Horrocks J et al. (November 2000). "Effects of digoxin on acute, atrial fibrillation-induced changes in atrial refractoriness" (pdf). Circulation 102 (20): 2503–2508. doi:10.1161/01.CIR.102.20.2503. PMID 11076824. 
  6. ^ Hallberg P, Lindbäck J, Lindahl B, Stenestrand U, Melhus H (October 2007). "Digoxin and mortality in atrial fibrillation: a prospective cohort study". European Journal of Clinical Pharmacology 63 (10): 959–971. doi:10.1007/s00228-007-0346-9. PMID 17684738. 
  7. ^ "The effect of digoxin on mortality and morbidity in patients with heart failure. The Digitalis Investigation Group". The New England Journal of Medicine 336 (8): 525–533. February 1997. doi:10.1056/NEJM199702203360801. PMID 9036306. 
  8. ^ a b Rossi S, ed. (2006). Australian Medicines Handbook 2006. Adelaide. ISBN 0-9757919-2-3. 
  9. ^ Tripathi KD (ed.). Essentials of Medical Pharmacology (6th ed.). New Delhi: Jaypee Publications. ISBN 81-8448-085-7. 
  10. ^ Moscovitz T, Aldrighi JM, Abrahanshon PA et al. (April 2005). "Repercussions of digoxin, digitoxin and estradiol on the endometrial histomorphometry of oophorectomized mice". Gynecology and Endocrinology 20 (4): 213–220. doi:10.1080/09513590400021219. PMID 16019364. 
  11. ^ Thompson DF, Carter JR (1993). "Drug-induced gynecomastia". Pharmacotherapy 13 (1): 37–45. PMID 8094898. 
  12. ^ Doering W, König E, Sturm W (1977). "(title in German)" [Digitalis intoxication: specificity and significance of cardiac and extracardiac symptoms. part I: Patients with digitalis-induced arrhythmias (author's transl)]. Zeitschrift für Kardiologie (in German) 66 (3): 121–128. PMID 857452. 
  14. ^ Leden I (1982). "Digoxin-hydroxychloroquine interaction?". Acta Medica Scandinavica 211 (5): 411–412. doi:10.1111/j.0954-6820.1982.tb01971.x. PMID 7113754. 
  15. ^ Flanagan RJ, Jones AL (2004). "Fab Antibody Fragments: Some Applications in Clinical Toxicology". Drug Safety 27 (14): 1115–1133. doi:10.2165/00002018-200427140-00004. PMID 15554746. 
  16. ^ Kaplanski J, Weinhouse E, Topaz M, Genchik G (1983). "Verapamil and digoxin: interactions in the rat". Research Communications in Chemical Pathology and Pharmacology 42 (3): 377–388. PMID 6665298. 
  18. ^ Tankenow, Roberta; Tamer, Helen R.; Streetman, Daniel S.; Smith, Scott G.; Welton, Janice L.; Annesley, Thomas; Aaronson, Keith D.; Bleske, Barry E. Interaction Study between Digoxin and a Preparation of Hawthorn (Crataegus oxyacantha), J Clin Pharmacol 2003;43:637-642
  19. ^ Hunt SA, Abraham, WT, Chin, MH et al. (September 2005). "ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society" (pdf). Circulation 112 (12): e154–e235. doi:10.1161/CIRCULATIONAHA.105.167586. PMID 16160202. 
  21. ^ "Recalls, Market Withdrawals & Safety Alerts". FDA. 2008-10-15. Retrieved 2011-11-08. 
  22. ^ "Urgent Digitek Digoxin Recall". U.S. Recall News. 2008-04-28. Retrieved 2009-07-25. 
  23. ^ "Patients Sue Icelandic Drugmaker Over Recalled Heart Drug". Wall Street Journal. 2008-05-09. Retrieved 2009-07-25. 
  24. ^ Zhang, H.; Qian, D. Z.; Tan, Y. S.; Lee, K.; Gao, P.; Ren, Y. R.; Rey, S.; Hammers, H.; Chang, D. (2008). "Inaugural Article: Digoxin and other cardiac glycosides inhibit HIF-1  synthesis and block tumor growth". Proceedings of the National Academy of Sciences (re: glycosides) 105 (50): 19579–19586. doi:10.1073/pnas.0809763105. PMC 2604945. PMID 19020076.  edit
  25. ^ Lopez-Lazaro M (March 2009). "Digoxin, HIF-1, and cancer" (pdf). PNAS 106 (9): E26. Bibcode:2009PNAS..106...26L. doi:10.1073/pnas.0813047106. PMC 2651277. PMID 19240208. 
  26. ^ Zhang, H.; Semenza, G. L. (2009). "Reply to Lopez-Lazaro: Evidence that digoxin inhibits human cancer". Proceedings of the National Academy of Sciences 106 (9): E27. doi:10.1073/pnas.0900125106.  edit

Further reading[edit]

  • Goldberger AD, Alexander GC. "Refitting the Foxglove: Digoxin Use in Contemporary Clinical

Practice". JAMA Internal Medicine. 

External links[edit]

  1. Protein Data Bank entry (useful for computational molecular dynamics): http://www.rcsb.org/pdb/explore.do?structureId=3B0W