Pharmacokinetics
Absorption:
After oral administration, digoxin is quickly and completely absorbed from the GI tract, but peak plasma concentrations are delayed for about 6 hours. Food slows down absorption, but not to the same extent.
Distribution:
Digoxin is widely distributed throughout the body after oral administration, with a volume of distribution of about 4 L/kg. Digoxin is released into breast milk after crossing the placenta. Between 25% and 40% of plasma proteins are bound.
Excretion and Metabolism:
Digoxin is converted to glucuronic acid and excreted by the kidney after being metabolized in the liver. Digoxin typically has a half-life of 24 to 48 hours, but in people with kidney disease, it can last up to 72 hours or longer. Digoxin excretion is reduced in congestive heart failure patients.
Digoxin Indications and Use
Digoxin is prescribed for the management of associated ventricular arrhythmias and the treatment of mild to moderate congestive heart failure (CHF). Digoxin has a positive inotropic effect on myocardial contractility in CHF without increasing myocardial oxygen demand. The enhanced sodium-potassium ATPase activity in cardiac muscle cell membranes and the increased calcium uptake by the sarcoplasmic reticulum are primarily responsible for the favorable inotropic effect. The end result is a decrease in ventricular filling pressures and an increase in cardiac output.
Digoxin has been used alone or in combination with other medications to treat CHF, and it has been linked to improvements in symptoms, weight loss, and exercise tolerance. However, data from large clinical trials have not been able to show a benefit in terms of mortality.
Digoxin is also recommended for the treatment of flutter and atrial fibrillation. Digoxin reduces automaticity and conduction velocity while having little impact on refractoriness in both arrhythmias. As a result, both the heart rate and the risk of thromboembolic complications in atrial fibrillation decrease.
Contraindications
Digoxin is not recommended for use in people with known drug hypersensitivity, ventricular fibrillation, or ventricular tachycardia. Digoxin should not be used in patients who have severe bradycardia (40 bpm) unless an artificial pacemaker is present and working.