Digitoxin is a cardiac glycoside used for the treatment of heart failure and certain kinds of heart arrhythmia. It is a phytosteroid and is similar in structure and effects to digoxin, though the effects are longer-lasting. Unlike digoxin, which is eliminated from the body via the kidneys, it is eliminated via the liver, and so can be used in patients with poor or erratic kidney function. While several controlled trials have shown digoxin to be effective in a proportion of patients treated for heart failure, the evidence base for digitoxin is not as strong, although it is presumed to be similarly effective. Medical uses Digitoxin is used for the treatment of heart failure, especially in people with impaired kidney function. It is also used to treat certain kinds of heart arrhythmia, such as atrial fibrillation. Contraindications Contraindications include problems with the heart rhythm, such as severe bradycardia (slow heartbeat), ventricular tachycardia (fast heartbeat caused by the ventricles), ventricular fibrillation, or first- to second-degree atrioventricular block, and certain electrolyte imbalances: hypokalemia (low blood potassium levels), hypomagnesemia (low magnesium), and hypercalcemia (high calcium). Adverse effects and toxicity Digitoxin exhibits similar toxic effects to digoxin, namely: anorexia, nausea, vomiting, diarrhea, confusion, visual disturbances, and cardiac arrhythmias. Antidigoxin antibody fragments, the specific treatment for digoxin poisoning, are also effective in serious digitoxin toxicity. Interactions Drugs that can increase digitoxin toxicity include: calcium substances that lower potassium or magnesium levels, such as diuretics and corticosteroids inhibitors of the liver enzyme CYP3A4, which slow down digitoxin metabolism; examples are the antibiotic clarithromycin, the antifungal itraconazole, and grapefruit juice inhibitors of the transporter protein P-gp, such as clarithromycin Beta blockers add to the bradycardia (slow heartbeat) caused by digitoxin. Drugs that can decrease the effectivity of digitoxin include: substances that increase potassium levels, such as potassium sparing diuretics inducers of CYP3A4 or P-gp, such as phenytoin, rifampicin and St John's Wort substances that bind digitoxin in the gut, such as aluminium containing antacids or colestyramine Pharmacology Mechanism of action Digitoxin inhibits the sodium-potassium ATPase in heart muscle cells, resulting in increased force of contractions (positive inotropic), reduced speed of electric conduction (negative dromotropic), increased excitability (positive bathmotropic), and reduced frequency of heartbeat (negative chronotropic). Pharmacokinetics The drug is almost completely absorbed from the gut. When in the bloodstream, 90 to 97% are bound to plasma proteins. Digitoxin undergoes enterohepatic circulation. It is metabolized in part by CYP3A4;