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Digitalis Toxicity

Digitalis Toxicity is a topic covered in the 5-Minute Clinical Consult.

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  • A life-threatening condition resulting from intoxication by digitalis (digoxin) when used for chronic therapy, from accidental or intentional overdose, or from ingestion of naturally occurring compounds containing cardiac glycosides (e.g., foxglove, oleander)
  • Can be acute or chronic
  • System(s) affected: cardiovascular, gastrointestinal (GI), ocular, central nervous system


~1.1% of outpatients on digitalis glycosides per year develop toxicity, with as many as 10–20% of nursing home residents annually experience some degree of digoxin-related toxicity.

  • In 2009, the American Association of Poison Control Centers’ National Poison Data System reported 2,550 cases of cardiac glycoside overdose, including 651 cases of plant cardiac glycoside exposure.
  • Digitalis toxicity is the fourth most common adverse drug reaction in hospitals (1).

Etiology and Pathophysiology

  • Digitalis inhibits Na+/K+-ATPase in myocytes, resulting in an increase in intracellular sodium and a decrease in the transmembrane sodium gradient.
  • Loss of the sodium gradient decreases the drive of the Na+/Ca2+ transporter, leading to increased intracellular calcium and thus increased inotropy.
  • At high/toxic digoxin concentrations, elevated intracellular calcium generates small depolarizations, and the additive effects of these depolarizations produce dysrhythmias.
  • Digitalis also acts on the parasympathetic system, resulting in increased vagal tone and slowing atrioventricular (AV) node conduction.
  • The combination of these effects can cause tachyarrhythmias and conduction block, which can present simultaneously.
  • Chronic therapy
  • Intentional overdose (suicide attempt)
  • Accidental overdose (children)
  • Prescription/administration error
  • Electrolyte disturbances—predominantly potassium balance
  • Renal failure (2) or any condition that decreases clearance of the drug
  • Poisoning with plants containing cardiac glycosides (e.g., oleander, foxglove, lily of the valley)
  • Concurrent use of medications
    • Antibiotics: rifampin, tetracycline, macrolides
    • Selective serotonin reuptake inhibitors (SSRIs)
    • Calcium channel blockers: diltiazem, verapamil
    • Antiarrhythmics: quinidine, amiodarone
    • Diuretics
    • β-Blockers

Risk Factors

  • Advanced age
  • Renal failure
  • Hypoxemia
  • Electrolyte disturbances
    • Hypokalemia
    • Hypomagnesemia
    • Hypernatremia
    • Hypercalcemia
  • Acid–base disturbances
  • Decompensating heart failure
  • Myocardial infarction
  • Myocarditis
  • Recent cardiac surgery
  • Hypothyroidism
  • Polypharmacy

General Prevention

  • Use caution when prescribing digitalis if the patient is taking medications that interfere with digoxin metabolism or clearance.
  • Adjust dosing when there are circumstances that increase total body levels of the drug (e.g., acute or chronic kidney disease), increase cardiac sensitivity (e.g., ischemia, myocarditis), increase bioavailability by altering gut flora (e.g., macrolides), or decrease protein binding (e.g., hypoalbuminemia).
  • Prescribe lower doses of digoxin (0.125 mg/day instead of 0.25 mg/day) (3). Digoxin is effective in heart failure at much lower levels than necessary for rate control in atrial fibrillation.

Commonly Associated Conditions

  • Renal failure
  • Heart failure
  • Dehydration
  • Polypharmacy

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Stephens, Mark B., et al., editors. "Digitalis Toxicity." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816010/all/Digitalis_Toxicity.
Digitalis Toxicity. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816010/all/Digitalis_Toxicity. Accessed March 22, 2019.
Digitalis Toxicity. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816010/all/Digitalis_Toxicity
Digitalis Toxicity [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 March 22]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816010/all/Digitalis_Toxicity.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Digitalis Toxicity ID - 816010 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816010/all/Digitalis_Toxicity PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -