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Digitoxin – Cardiac Glycoside: Effects & Uses

Digitoxin is a cardiac glycoside derived from the foxglove plant, used to treat heart failure and atrial fibrillation by strengthening heart contractions.

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Things worth knowing about "Digitoxin"

Digitoxin is a cardiac glycoside derived from the foxglove plant, used to treat heart failure and atrial fibrillation by strengthening heart contractions.

What is Digitoxin?

Digitoxin is a cardiac glycoside derived from the plant Digitalis purpurea (common foxglove). It belongs to the class of digitalis preparations and is used in cardiology to strengthen the contractile force of the heart and regulate heart rhythm. Compared to the related compound digoxin, digitoxin has a significantly longer half-life and is metabolized primarily by the liver rather than excreted by the kidneys.

Indications

Digitoxin is primarily used for the following conditions:

Chronic heart failure, particularly when the pumping function of the heart is reduced
Atrial fibrillation and atrial flutter for ventricular rate control
Certain forms of supraventricular tachycardias (rapid heart rhythms originating in the upper chambers of the heart)

Mechanism of Action

Digitoxin works by inhibiting the sodium-potassium ATPase enzyme located in the membrane of heart muscle cells. This enzyme normally pumps sodium out of and potassium into the cell. When inhibited, intracellular sodium levels rise, which indirectly leads to an increase in intracellular calcium. The elevated calcium concentration enhances the force of heart muscle contractions – a process known as a positive inotropic effect. Additionally, digitoxin slows the conduction of electrical impulses through the atrioventricular (AV) node via vagal stimulation, resulting in a reduction of heart rate (a negative chronotropic effect).

Dosage and Administration

Digitoxin is typically administered as an oral tablet. Dosing is individualized based on clinical response and serum drug levels. Typical maintenance doses range from 0.05 to 0.1 mg per day. Because digitoxin is primarily metabolized by the liver, it can be used in patients with impaired kidney function – an important advantage over digoxin, which relies on renal excretion.

Due to its long half-life of approximately 5 to 7 days, digitoxin accumulates gradually in the body. Regular monitoring of serum levels is therefore essential to prevent toxicity.

Side Effects

Digitoxin has a narrow therapeutic index, meaning the difference between an effective dose and a toxic dose is small. Possible side effects include:

Cardiac arrhythmias (e.g., bradycardia, ventricular extrasystoles, AV block)
Gastrointestinal symptoms: nausea, vomiting, loss of appetite, diarrhea
Neurological symptoms: headache, fatigue, dizziness, visual disturbances (yellow-green vision, blurred vision)
Digitalis toxicity: overdose can lead to life-threatening cardiac arrhythmias

Drug Interactions

Digitoxin can interact with numerous medications:

Potassium-lowering drugs (e.g., diuretics such as furosemide): increased risk of digitalis toxicity due to hypokalemia
Antiarrhythmic agents (e.g., amiodarone, quinidine): can raise digitoxin serum levels
Calcium channel blockers and beta-blockers: can enhance bradycardic effects
Antibiotics (e.g., erythromycin): may affect the absorption and plasma levels of digitoxin

Contraindications

Digitoxin should not be used in patients with:

Known hypersensitivity to cardiac glycosides
Ventricular tachycardia or ventricular fibrillation
AV block of the second or third degree (without a pacemaker)
Hypertrophic obstructive cardiomyopathy
Severe hypokalemia or hypercalcemia

References

Mutschler, E. et al. – Arzneimittelwirkungen: Pharmakologie, Klinische Pharmakologie, Toxikologie. Wissenschaftliche Verlagsgesellschaft, 10th edition (2013).
Frishman, W.H. & Sica, D.A. – Cardiovascular Pharmacotherapeutics. Cardiology Clinics (2019).
European Heart Rhythm Association (EHRA) / ESC Guidelines on the management of atrial fibrillation. European Heart Journal (2020). DOI: 10.1093/eurheartj/ehaa612

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