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Digoxin is an antiarrhythmic that is commonly used to treat heart failure and arrhythmia. Discovered and isolated from the foxglove plant in 1930, digoxin is one of the most commonly used cardiac medications in the world. According to pediatric cardiologist and intensive care doctor, Dr. Darren Klugman, digoxin can be an important therapy for patients in the pediatric intensive care unit if providers have a comprehensive understanding of its mechanism of action and potential side effects.
Despite its widespread use, the mechanism of action of digoxin is not commonly understood. The mechanism of action of digoxin occurs through the inhibition of the sodim potassium adenosine triphosphatase (Na+/K+ ATPase) transporter on the myocardial cell membrane. The inhibition of the Na+/K+ ATPase leads to increase in intracellular myocardial sodium concentration which in turn leads to alterations in the sodium calcium transporter on the myocardial cell membrane. Altering the ion concentrations across the myocardial cell membrane, intracellular sodium concentration increases which results in a decrease in the gradient for sodium and calcium exchange across the sodium-calcium exchanger. Intracellular calcium concentration increases which thereby increases calcium availability for binding with contractile proteins and lengthens phase 0 and phase 4 of the cardiac action potential which decreases heart rate. Furthermore, intracellular calcium concentration also leads to increase calcium stores in the sarcoplasmic reticulum. According to Dr. Darren Klugman, the effect of digoxin on the parasympathetic nervous system and subsequently the conduction at the AV node also contributes to the reduction in heart rate with the use of digoxin.
Digoxin is approximately 30% protein bound with an elimination half-life of about 30 hours in patients with preserved renal function. While usually given orally, intravenous administration of digoxin can be done safely; however, must be done slowly and should be reserved for patients unable to tolerate oral medications. Impaired renal function leads to reduction in volume of distribution and increase in half-life which necessitates dosing reduction. “Pediatric patients in the cardiac intensive care unit are particularly vulnerable to alterations in renal function which will impact the pharmacokinetics of digoxin, and providers must understand this physiological interaction to minimize adverse drug reactions” says Dr. Darren Klugman.
According to Dr. Darren Klugman, the most common side effects of digoxin in the pediatric cardiac intensive care unit occur because of alterations in renal function and drug interactions which are unrecognized. Changes in renal function alter digoxin clearance and can change serum electrolyte concentrations which can lead to life threatening digoxin toxicity. Digoxin side effects most commonly noted in the pediatric cardiac ICU include arrhythmia and bradycardia as a result of alterations in the cardiac action potential as well as changes in serum and myocardial electrolyte concentrations. While patients are being given digoxin, it is important to monitor serum potassium levels for hypokalemia and hyperkalemia and adjust digoxin dosing particularly when used in conjunction with additional antiarrhythmics such as amiodarone and verapamil.
Digoxin toxicity often presents with arrhythmia and/or life-threatening bradycardia. Classic ECG findings consistent with digoxin toxicity include ST depression, high degree AV block and any combination of atrial or ventricular tachydysrhythmias. Treatment requires prompt recognition of the symptoms of digoxin toxicity and immediate discontinuation of therapy with administration of antidigoxin (Digifab or Digibind).