Digoxin

Digoxin is a cardiac glycoside derived from the plant foxglove that primarily works by inhibiting the Na+/K+ ATPase in the myocardium.​

Mechanism: Digoxin has positive inotropic effects and negative chronotropic effects ​

• Binds to and inhibits the Na+/K+ pump on the myocyte cell membrane (competes with the K+ ion) Increases intracellular Na+ concentration.​
• Reduces the extrusion of intracellular Ca2+ via the Na+/Ca2+ exchange transporter Increased Ca2+ is stored in the sarcoplasmic reticulum Increased amounts of Ca2+ released during each action potential force of contraction increased​.
•  Digoxin also increases vagal tone by enhancing Ach release at muscarinic receptors, thus slowing the heart rate, atrioventricular (AV) conduction, and the AV nodal refractory period.​​

Indications: Heart failure, persistent and permanent atrial fibrillation and flutter.​

Note: In heart failure digoxin is useful in patient with reduced ejection fraction, with an ejection fraction below 40%. However, it has no benefit in mortality reduction.​

• Digoxin can only be used as monotherapy in sedentary patients because it controls ventricular response at rest.

Monitoring: Digoxin has narrow therapeutic index. Narrow therapeutic index means difference between the effective therapeutic dose and the potentially toxic dose is relatively small. This narrow window makes proper dosing and monitoring critically important to ensure the medication’s safety, effectiveness and to prevent toxicity. The therapeutic plasma levels of digoxin are usually between 1.0-1.5 nmol/l. The likelihood of toxicity rises dramatically at levels above 2 nmol/l.​

Dose adjustments in renal failure and liver failure:​

Renal failure: Digoxin is excreted renally, and impaired renal function can cause increased digoxin levels and leads to digoxin toxicity. In this case the patient should have their digoxin dose reduced and their digoxin level and electrolytes should be carefully monitored.​

Liver failure: Liver failure has little influence on digoxin metabolism or clearance; therefore, no dose adjustment is necessary.​

Digoxin toxicity: Precipitated by hypokalemia or drugs causing hypokalemia, hypercalcemia, acidosis and renal failure.​

The features of digoxin toxicity include:​

•  Hyperkaliemia ​
•  Nausea, vomiting and diarrhea​.
• Abdominal pain​
• Confusion, dizziness and psychosis​
• Tachyarrhythmias or bradyarrhythmia’s​
•  Xanthopsia (yellow-green vision)​

Treatment: Digoxin immune fab is the reversal agent (Antidote) of digoxin toxicity.​