Products
Digoxin is commercially available in many countries in tablet form and as a solution for injection and has been approved since 1960 (Digoxin Juvisé, original: Sandoz).
Structure and properties
Digoxin (C41H64O14, Mr = 780.96 g/mol) is a cardiac glycoside obtained from the leaves of . It is composed of three sugar units (hexoses) and the aglycone digoxigenin. It exists in the form of colorless crystals or as a white powder that is practically insoluble in water.
Effects
Digoxin (ATC C01AA05) exerts numerous effects on the heart muscle. Among the most important are:
- Increase in contractile force and velocity (positive inotropic).
- Decrease in heart rate (negative chronotropic).
- Slowing of excitation conduction (negative dromotropic).
- Increase in excitability, especially of the ventricular muscles (positive bathmotropic).
The result of these effects is increased stroke volume, which improves renal blood flow and increases urine output. Digoxin also has direct renal effects such as inhibition of Na+ reabsorption. The positive inotropic effect is detectable only in the healthy myocardial fiber.This explains the decreasing importance of cardiac glycosides in the treatment of heart failure today. It is also disadvantageous that the digitalis effect leads to an increased oxygen demand of the myocardial cell, which may be particularly unfavorable in the context of acute or chronic myocardial ischemia (e.g., coronary artery disease).
Mechanism of Action
The effects of digoxin are based on inhibition of the membrane-bound alpha subunits of Na+/K+-ATPase. This leads indirectly to inhibition of the Na+-and Ca2+-exchange, resulting in increased Ca2+ concentration in cardiac myocytes and consequent uptake of Ca2+ into the sarcoplasmic reticulum results. As a result, the contractile force and velocity of the myocardium increases. Inhibition of Na+/K+-ATPase is also thought to improve baroreceptor sensitivity, which may explain the neurohormonal effects of digoxin.
Indications
For the treatment of acute and chronic heart failure and atrial fibrillation and flutter.
Dosage
According to the SmPC. Because of the narrow therapeutic range, carefully monitored adjustment to the individual dose is necessary. Adjust dose if renal function is impaired.
Contraindications
Digoxin is contraindicated in hypersensitivity, suspected digitalis intoxication, and in patients with cardiac arrhythmias such as ventricular tachycardia and fibrillation, grade II or III AV block, or dilatation of the vascular wall of the aorta at the level of the thorax (thoracic aortic aneurysm) and thickening of the myocardium with increasing obstruction (hypertrophic cardiomyopathy). Digoxin should also not be taken in the event of hypokalemia, hypercalcemia, hypomagnesemia, and oxygen deficiency. For complete precautions, see the drug label.
Interactions
Digoxin is excreted largely unchanged in the urine. Only about 16% of the absorbed amount is metabolized. Digoxin is a substrate of P-glycoprotein. Inhibitors of this transporter may increase serum concentrations of digoxin. Calcium should not be administered intravenously due to an increase in glycoside toxicity. Drugs such as diuretics and laxatives that affect the electrolyte balance result in an enhancement of glycoside toxicity due to drug-induced hypokalemia and hypomagnesemia, respectively. Concomitant administration of calcium channel blockers, antiarrhythmic drugs such as quinidine or amiodarone, captopril, itraconazole, atropine, spironolactone, and certain antibiotics can greatly increase digoxin concentrations. Beta-blockers enhance bradycardic effects, and agents such as suxamethonium chloride, reserpine, tricyclic antidepressants, sympathomimetics, and phosphodiesterase inhibitors promote arrhythmias. Concomitant use of potassium-level-increasing drugs decreases the positive ionotopic effect of digoxin.
Adverse effects
As a result of the narrow therapeutic window, adverse effects and signs of intoxication occur frequently with digoxin.Common adverse effects include loss of appetite, cardiac arrhythmias, nausea, vomiting, diarrhea, facial pain, headache, fatigue, weakness, and drowsiness. Rarely, confusion, disorientation, perceptual disturbances, psychosis, visual disturbances (color vision), and abdominal pain may occur. In very rare cases, enlargement of the male mammary gland, convulsions, hypersensitivity reactions, and blood count disorders have also been observed.