Digoxin is a drug commonly used in the treatment of a variety of heart conditions. Classified as a cardiac glycoside, it is derived from the foxglove plant (scientific name: Digitalis lanata), and is thus also called digitalis.
Digoxin increases heart contractility (positive inotropic effect), lowers the heart rate (negative chronotropic effect) and slows atrioventricular (AV) conduction (negative dromotropic effect). This is done indirectly through the autonomic nervous system as a vagomimetic effect and through inhibition of Na+-K+-ATPase in heart muscle.
Primary indications include chronic heart failure, especially in the presence of systolic dysfunction; supraventricular arrhythmia in which the influence of AV conduction is significant; and atrial fibrillation and flutter accompanied by a rapid ventricular rhythm. It may be administered orally or intravenously.
Most side effects of digoxin are due to overdose, although anorexia, nausea, vomiting and headache may also occur at therapeutic doses after rapid absorption. Other non-cardiac side effects include diarrhea, weakness, apathy, fatigue, and CNS effects such as dizziness, confusion, depression, delirium, psychosis and visual disturbances (especially impaired color perception). Rarely, abdominal pain, intestinal necrosis, allergic reactions such as rashes and thrombocytopenia, and gynecomastia may also occur.
Frequent cardiac side effects include various types of arrhythmias (especially ventricular extrasystoles), heart block and atrial tachycardia with a certain degree of AV block. Rapid intravenous (IV) injection may result in vasoconstriction with hypertension and reduced coronary perfusion. In children, side effects and associated arrhythmias (especially conduction disturbances and supraventricular tachyarrhythmias) are different from those in adults, with bradycardia being the first and most common manifestation of overdose.
Digoxin should not be given to patients with pheochromocytoma or tachyarrhythmias. Other contraindications include hypertrophic obstructive cardiomyopathy, arrhythmias caused by cardiac glycoside intoxication, 2nd- or 3rd-degree AV block, hypersensitivity to digitalis, ventricular tachycardia or ventricular fibrillation. Extra caution is advised in patients with constrictive pericarditis and 1st-degree AV block.
Continuous monitoring of blood pressure, and central venous pressure if possible, is necessary after starting therapy. The recommended initial infusion rate is 2-5 mcg/kg body weight/min, with the dose gradually increased until blood pressure and diuresis have been corrected. The desired therapeutic effect typically occurs at an infusion rate of less than 20 mcg/kg/min. In some cases of severe circulatory insufficiency, however, doses of up to 50 mcg/kg/min may be necessary. In the presence of shock caused by heart failure, the dose should be kept as low as possible. The desired therapeutic effect is usually achieved at an infusion rate of 500-1000 mcg/min.
Because it has no known adverse effects on the fetus, digoxin can be used during pregnancy while the maternal digoxin blood level is within normal limits. However, it can cross the placenta and reach fetal circulation in the same plasma concentration as that of the mother. The fetal heart rate should therefore be carefully monitored, especially in the peripartal period. Dosages may need to be adjusted due to rapid excretion of digoxin during pregnancy. Digoxin is excreted in breast milk in such small amounts that no adverse effects on breastfeeding infants are expected.
Hypokalemia-inducing substances such as certain laxatives and diuretics, amphotericin B, corticosteroids and lithium salts can accelerate the occurrence of cardiac glycoside intoxication. Parenteral calcium administration and suxamethonium also increase the toxicity of digoxin.
Quinidine, hydroxychloroquine, propafenone, spironolactone, amiodarone, cyclosporine, verapamil, diltiazem, itraconazole, nitrendipine and nisoldipine can raise blood levels by inhibiting the excretion and/or displacement digoxin from tissue binding. Amiodarone and nefazodone can increase digoxin levels by 80% and 15-30%, respectively.
Prazosin, quinine, alprazolam, indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) may increase digoxin concentration. Conversely, rifampicin, phenytoin, and St. John's wort (Hypericum perforatum) may decrease digoxin levels. When using antibiotics (erythromycin, tetracycline), the degradation of digoxin by intestinal bacteria declines due to the change in intestinal flora, so more drug becomes available for absorption. Simultaneous use of sympathomimetics increases the risk of arrhythmias.
When digoxin is given orally, propantheline and possibly other parasympathicolytics may increase digoxin levels by increasing gastrointestinal absorption. Cholestyramine, neomycin, penicillamine, metoclopramide, sulfasalazine, kaolin, adsorptive carbon, cytostatics and liquid antacids reduce absorption.
Kinetic data for digoxin are as follows:
Absorption: Oral 55-75%.
Tmax = 1-2 hours orally.
Protein binding = 20-30%.
Therapeutic plasma levels: 0.5-2 ng/mL.
Vd = 7.3 L/kg, the concentration in the heart is approximately 30 times higher than that in the systemic circulation.
Concomitant intake of food slows absorption.
Digoxin is eliminated 60-75% unchanged in the urine.
T1/2 = approximately 36 hours with normal renal and thyroid function.
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