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For centuries, digitalis glycosides have been recognized for their medicinal benefits and potential toxicity. Digitalis preparations, such as digoxin, are used for the treatment of supraventricular tachydysrhythmias and congestive heart failure. In addition to their availability as pharmaceuticals, cardiac glycosides are also found in plants such as foxglove, oleander, and lily of the valley. Between 1994 and 2004, digoxin use decreased in the U.S., leading to an overall decline in the incidence of toxicity.1 Digitoxin, a cardiac glycoside similar in structure to digoxin but with a longer half-life, is no longer commercially available in the U.S., but is available in Canada and elsewhere in the world.

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Digoxin is absorbed rapidly from the GI tract with a bioavailability of between 75% and 95%, depending on the formulation. Once absorbed, digoxin distributes slowly into the tissues over a period of 6 to 8 hours. Extensive tissue binding produces a large volume of distribution, about 7 L/kg in therapeutic dosing and 5 to 6 L/kg in acute overdoses. Elimination is primarily through renal excretion, with a half-life of 36 to 48 hours in patients with normal renal function and 3.5 to 5 days in anuric patients. As a comparison, the elimination of digitoxin is via hepatic metabolism, with a half-life of 5 to 7 days in adults and up to 12 to 37 days in individuals older than 80 years old.

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The pharmacologic effects of digoxin and other cardiac glycosides are due to binding with the membrane-bound α subunits of sodium-potassium adenosine triphosphatase (ATPase) pump, inhibiting the function of this enzyme.2 Inhibition of the sodium-potassium ATPase pump leads to increased concentrations of intracellular sodium. This increase in intracellular sodium concentrations relative to extracellular concentrations reduces the electrochemical gradiant across the plasma membrane and results in a net increase in intracellular calcium ions via the sodium-calcium exchanger. The final result is an increase in the intracellular calcium concentration available to contractile proteins, resulting in increased inotropy.2

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Inhibition of the sodium-potassium ATPase pump can also affect the resting transmembrane potential and action potential of electrically excitable cells. This activity produces an increase in vagal tone that decreases conduction through the atrioventricular node and is used therapeutically for ventricular rate control in the treatment of supraventricular tachyarrhythmias, but may result in various bradyarrhythmias in toxicity.3 Automaticity of cells with spontaneous depolarization is enhanced by digoxin, and various forms of cardiac ectopy and tachyarrhythmias can be seen with digoxin toxicity. Intracellular calcium overload can create delayed after-depolarizations, causing electrical oscillations in cell membranes that give rise to triggered dysrhythmias.4

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Digoxin has a narrow therapeutic index, and toxicity results from an exaggeration of its pharmacologic activity. In addition to cardiac manifestations such as syncope and dysrhythmia, digoxin toxicity may present with GI distress, dizziness, headache, weakness, syncope, and seizures. Reported psychiatric symptoms include confusion, disorientation, delirium, and hallucinations. Thus, an elderly patient taking digoxin who presents ...

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