Clinical Significance

Digoxin is a widely prescribed steroidal cardio-active glycoside. It acts by binding and inhibiting the Na+/K+‑ATPase which in the end increases the intracellular Ca2+ concentration. This results in a positive inotrope effect which makes digoxin a beneficial drug for heart failure. It improves the strength of myocardial contraction and results in the beneficial effects of increased cardiac output, increased Left Ventricular Ejection Fraction, and decreased Pulmonary Capillary Wedge pressure. Digoxin therapy also results in stabilized and slowed ventricular pulse rate. 

Although the availability of crystalline digoxin has permitted the standardization of drug dosage, therapeutic administration inadvertently, yet frequently, results in toxicity. Importantly, symptoms of digoxin toxicity often mimic the cardiac arrhythmias for which the drug was originally prescribed. Digoxin concentrations of 0.9‑2.0 ng/mL in serum or plasma were considered to be therapeutic. However, later studies observed an increased risk for mortality for digoxin concentrations of 1.2 ng/mL and higher. The 2013 AHA/ACC guidelines mentioned that doses of digoxin that achieve a plasma concentration of drug in the range of 0.5 to 0.9 ng/mL are suggested, given the limited evidence currently available and that overt digoxin toxicity is commonly associated with serum digoxin levels > 2 ng/mL.

_{Source: Roche cobas Elecsys Digoxin method sheet, V 4.0 2022-10}