Digitoxin

Digitoxin is a cardiac glycoside derived from Digitalis species, most notably foxglove. It has historically been used to treat congestive heart failure and to control ventricular rate in atrial fibrillation, though its use has declined with the availability of other therapies. It may still be encountered in some regimens for symptom management in select patients.

Mechanism of action: Digitoxin inhibits the Na+/K+-ATPase pump on cardiac myocytes, increasing intracellular sodium and reducing the activity of the Na+/Ca2+ exchanger. This leads to higher intracellular calcium and enhanced myocardial contractility (positive inotropy). In addition, digitoxin increases parasympathetic tone, which can slow AV nodal conduction and influence heart rate.

Pharmacokinetics: Digitoxin is absorbed from the gut and binds extensively to serum albumin. It has a long half-life, typically measured in days, and is cleared mainly by the liver with biliary excretion; renal clearance plays a smaller role. These characteristics mean digitoxin can accumulate, particularly in hepatic impairment, and dosing must account for this.

Clinical use and monitoring: Because of a narrow therapeutic window, dosing is individualized based on body weight, age, renal and hepatic function, and electrolyte status. Electrolyte disturbances, especially hypokalemia from diuretics, increase the risk of toxicity. Regular monitoring of clinical response and, when possible, drug levels and electrolyte balance is advised.

Toxicity and management: Digitalis toxicity presents with gastrointestinal symptoms, confusion, visual disturbances, and a range of arrhythmias. Management includes discontinuation of digitoxin, electrolyte correction, and, in severe cases, administration of digoxin-specific antibody fragments (though affinity for digitoxin is lower). Supportive measures and avoidance of interacting drugs are important to minimize risk.