Pharmacokinetics and mechanism of action
After entering the gastrointestinal tract, digoxin is absorbed quite well, although its bioavailability can vary from 60 to 85%. In blood plasma, the drug binds moderately to proteins — at 25–30%.
A crucial feature of the substance is that it undergoes virtually no metabolism in the body. The main part of the dose (70–80%) is excreted by the kidneys in its original form.
Clinical rule: in renal failure, the drug clearance drops sharply. To avoid dangerous accumulation of the substance in tissues, the dosage must be reduced.
The onset speed of the effect depends on the route of administration:
- Intravenous: starts working in 20–30 minutes, peak is reached by 3 hours.
- Oral: effect starts in 1–2 hours, maximum — in 8 hours.
After complete withdrawal of the drug, its effect persists for another 2 to 7 days (provided healthy kidneys).
Indications and therapy risks
The drug is prescribed for the following cardiovascular pathologies:
- Chronic heart failure (tableted oral forms are used).
- Acute heart failure (requires intravenous administration for a rapid effect).
- Tachy-form of atrial fibrillation.
The main danger during treatment is the high probability of material accumulation. Due to the long half-life ($t_{1/2}$ is 32–48 hours) and binding to plasma proteins, the substance is capable of physically accumulating in the body, which can lead to severe intoxication.
Related woolly foxglove drugs
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 kind of "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. In terms of kinetics and dynamics, the drug is identical to the basic substance.
- Lanatoside C (Cedalanid). Primary (genuine) glycoside. It differs by lower oral bioavailability (only 30–40%) and weak protein binding (20–25%). In the body, it also turns into digoxin and is excreted by the kidneys. The half-life is slightly shorter — 28–36 hours. Its main advantage is a "softer" effect, which is why it often becomes the drug of choice for elderly patients.
Digitoxin: purple foxglove glycoside
Unlike digoxin, digitoxin is obtained from purple foxglove (Digitalis purpurea). This is a lipophilic and non-polar compound, which completely changes its pharmacokinetic profile.
- Absorption and distribution: absorbed from the gastrointestinal tract almost completely (bioavailability 95–100%). Plasma protein binding is extremely high — 90–97%.
- Metabolism: broken down primarily in the liver.
- Enterohepatic recirculation: part of the drug is excreted with bile into the intestine, from where it is reabsorbed into the blood and returns to the liver. This closed loop greatly delays the substance in the body.
Digitoxin action develops slowly (latent period 2–4 hours, peak in 8–12 hours), but lasts an incredibly long time — from 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 cumulation among all cardiac glycosides, and the risk of intoxication with its intake is maximal.
Briefly: answers to topical questions
What are the symptoms of glycoside intoxication in digoxin overdose?
Glycoside intoxication in digoxin overdose manifests with cardiac and extracardiac symptoms. Among iatrogenic manifestations and dyspeptic disorders, nausea and vomiting are noted. The development of AV conduction disorders is also possible.
What are the contraindications to prescribing digoxin?
Digoxin is contraindicated in atrial fibrillation/flutter in patients with WPW syndrome, as it can improve conduction through accessory pathways and cause an increase in ventricular rate. Cardiac glycosides are also contraindicated in AV block. In patients with hypertrophic cardiomyopathy and stable sinus rhythm, the use of cardiac glycosides is not recommended.
What is the mechanism of action of digoxin at the cellular level?
At the cellular level, the mechanism of action of cardiac glycosides consists in increasing the level of intracellular calcium. This process leads to the realization of a positive inotropic effect, as well as negative chronotropic and dromotropic effects in the myocardium.
Which drugs are used as antidotes for digoxin poisoning?
In foxglove (digitalis) glycoside intoxication, digoxin antibody preparations are most effective.
To avoid confusing the elimination pathways: Digoxin is eliminated by the kidneys (virtually un metabolized), while digitoxin is processed in the liver (has enterohepatic circulation).
Class and exam questions
Why is it necessary to reduce the dose of digoxin in renal failure?
Because 70–80% of the drug is excreted by the kidneys unchanged. When their function decreases, clearance drops, and a high risk of dangerous substance accumulation (material cumulation) arises.
How does the absorption mechanism of acetyldigoxin B differ?
The acetyl group acts as a carrier, improving resorption in the intestine. In the intestinal wall itself, it is cleaved (deacetylation occurs), and conventional digoxin enters the blood.
Which glycoside is better to prescribe to an elderly patient and why?
Lanatoside C (cedalanid) is preferred. It has a milder effect and is generally better tolerated by elderly patients.
Why does digitoxin act for so long (up to 21 days)?
This is due to its high lipophilicity, strong binding to plasma proteins (up to 97%), and the presence of enterohepatic recirculation — a constant cycle of the substance between the liver and intestines.
What else to study on this topic
- Mechanism of development of material cumulation of cardiac glycosides
- Symptoms and principles of treatment of glycoside intoxication
- Enterohepatic recirculation: physiological meaning and impact on pharmacokinetics
- Differences between genuine (primary) and secondary glycosides
- Features of glycoside use in tachyarrhythmic atrial fibrillation
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