What are the symptoms of cardiac glycoside toxicity from digoxin overdose?

Digitalis toxicity presents with cardiac and extracardiac symptoms. Iatrogenic manifestations and dyspeptic disorders include nausea and vomiting. AV conduction disturbances may also develop.

What are the contraindications to digoxin administration?

Digoxin is contraindicated in atrial fibrillation/flutter in patients with Wolff-Parkinson-White (WPW) syndrome because it can enhance conduction through accessory pathways and dramatically increase ventricular rate. Cardiac glycosides are also contraindicated in AV block. Patients with hypertrophic cardiomyopathy and sinus rhythm generally should not receive cardiac glycosides.

What is the cellular mechanism of action of digoxin?

At the cellular level, the mechanism of cardiac glycosides involves increasing intracellular calcium levels. This process leads to a positive inotropic effect, along with negative chronotropic and dromotropic effects on the myocardium.

What drugs are used as antidotes for digoxin poisoning?

Digoxin-specific antibody fragments (digoxin immune Fab) are the most effective treatment for digitalis glycoside toxicity.

Why must the digoxin dose be reduced in renal failure?

Because 70–80% of the drug is excreted unchanged by the kidneys. When renal function declines, clearance drops, creating a high risk of dangerous drug accumulation (material accumulation).

How does the absorption mechanism of acetyldigoxin B differ?

The acetyl group acts as a carrier, improving intestinal absorption. Within the intestinal wall itself, it is cleaved (deacetylation occurs), releasing regular digoxin into the bloodstream.

Which glycoside is preferred for an elderly patient and why?

Lanatoside C (celanid) is preferred. It has a milder effect and is generally better tolerated by older patients.

Why does digitoxin have such a long duration of action (up to 21 days)?

This is due to its high lipophilicity, strong plasma protein binding (up to 97%), and enterohepatic recirculation—a continuous loop of the drug between the liver and intestines.

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Digoxin

*Digoxinum*

For medical students2 min readUpdated 2026-10-10

Digoxin is the most widely used cardiac glycoside in clinical practice, derived from woolly foxglove (Digitalis lanata). It is prescribed for acute and chronic heart failure, as well as supraventricular arrhythmias, requiring strict dosage monitoring due to the risk of accumulation in the body.

Bioavailability60–85% orally (depends on the tablet manufacturer)

Excretion70–80% excreted unchanged by the kidneys

Half-life32–48 hours with normal renal function

Major RiskMaterial accumulation and severe toxicity

Pharmacokinetics and Pharmacodynamics

After oral administration, digoxin is absorbed quite well, though its bioavailability ranges from 60 to 85%. Plasma protein binding is moderate, at 25–30%.

A crucial property of the substance is that it undergoes virtually no hepatic metabolism. The majority of the dose (70–80%) is excreted unchanged by the kidneys.

Clinical rule: in renal failure, drug clearance drops sharply. To prevent dangerous tissue accumulation, the dosage must be reduced.

The onset of action depends on the route of administration:

Intravenous: starts working in 20–30 minutes, peak effect by 3 hours.
Oral: effect starts in 1–2 hours, maximum at 8 hours.

After complete discontinuation, its effects persist for another 2 to 7 days (assuming healthy kidneys).

Indications and Therapy Risks

The drug is indicated for the following cardiovascular conditions:

Chronic heart failure (oral formulations are used).
Acute heart failure (requires intravenous administration for rapid effect).
Tachyarrhythmic atrial fibrillation.

The main hazard during therapy is the high probability of material accumulation. Due to its long half-life ($t_{1/2}$ of 32–48 hours) and plasma protein binding, the substance can physically accumulate in the body, leading to severe toxicity.

Related Compounds of Woolly Foxglove

In addition to digoxin itself, other derivatives of Digitalis lanata are used in medicine:

Acetyldigoxin B (Novodigal). This is an acetylated derivative. The acetyl group acts as a "carrier," significantly improving absorption in the small intestine. Upon passing through the intestinal wall, almost complete deacetylation occurs, and pure digoxin enters the systemic circulation. Its kinetics and dynamics are identical to the base substance.
Lanatoside C (Celanid). A primary (genuine) glycoside. It features lower oral bioavailability (only 30–40%) and weaker protein binding (20–25%). In the body, it also converts to digoxin and is excreted by the kidneys. The half-life is slightly shorter at 28–36 hours. Its main advantage is a "softer" effect, making it frequently the drug of choice for elderly patients.

Digitoxin: Glycoside of Purple Foxglove

Unlike digoxin, digitoxin is derived from purple foxglove (Digitalis purpurea). It is a lipophilic and nonpolar compound, which completely alters its pharmacokinetic profile.

Absorption and distribution: absorbed almost completely from the GI tract (bioavailability 95–100%). Plasma protein binding is extremely high at 90–97%.
Metabolism: metabolized primarily in the liver.
Enterohepatic circulation: a portion of the drug is excreted via bile into the intestine, reabsorbed into the blood, and returned to the liver. This cycle significantly delays drug elimination.

Digitoxin's onset of action is slow (latent period 2–4 hours, peak at 8–12 hours), but its duration is remarkably long—lasting 14 to 21 days after a single dose. The half-life is 4–7 days. Due to these parameters, digitoxin has the highest capacity for material accumulation among all cardiac glycosides, and the risk of toxicity is maximal.

Mnemonic

To remember excretion pathways: DigOxin is excreted by the Okidneys (minimal metabolism), while Digitoxin is processed in the liver (undergoes enterohepatic circulation).

Frequently asked questions

What are the symptoms of cardiac glycoside toxicity from digoxin overdose?: Digitalis toxicity presents with cardiac and extracardiac symptoms. Iatrogenic manifestations and dyspeptic disorders include nausea and vomiting. AV conduction disturbances may also develop.
What are the contraindications to digoxin administration?: Digoxin is contraindicated in atrial fibrillation/flutter in patients with Wolff-Parkinson-White (WPW) syndrome because it can enhance conduction through accessory pathways and dramatically increase ventricular rate. Cardiac glycosides are also contraindicated in AV block. Patients with hypertrophic cardiomyopathy and sinus rhythm generally should not receive cardiac glycosides.
What is the cellular mechanism of action of digoxin?: At the cellular level, the mechanism of cardiac glycosides involves increasing intracellular calcium levels. This process leads to a positive inotropic effect, along with negative chronotropic and dromotropic effects on the myocardium.
What drugs are used as antidotes for digoxin poisoning?: Digoxin-specific antibody fragments (digoxin immune Fab) are the most effective treatment for digitalis glycoside toxicity.
Why must the digoxin dose be reduced in renal failure?: Because 70–80% of the drug is excreted unchanged by the kidneys. When renal function declines, clearance drops, creating a high risk of dangerous drug accumulation (material accumulation).
How does the absorption mechanism of acetyldigoxin B differ?: The acetyl group acts as a carrier, improving intestinal absorption. Within the intestinal wall itself, it is cleaved (deacetylation occurs), releasing regular digoxin into the bloodstream.
Which glycoside is preferred for an elderly patient and why?: Lanatoside C (celanid) is preferred. It has a milder effect and is generally better tolerated by older patients.
Why does digitoxin have such a long duration of action (up to 21 days)?: This is due to its high lipophilicity, strong plasma protein binding (up to 97%), and enterohepatic recirculation—a continuous loop of the drug between the liver and intestines.

Go deeper

Mechanism of material accumulation of cardiac glycosides
Symptoms and management principles of digitalis toxicity
Enterohepatic recirculation: physiological significance and impact on pharmacokinetics
Differences between genuine (primary) and secondary glycosides
Use of cardiac glycosides in tachyarrhythmic atrial fibrillation