The medicinal benefits of cardiac glycosides have been recognized for centuries, and even with other alternative medications, digitalis preparations, such as digoxin, are still used for the treatment of atrial fibrillation and symptomatic congestive heart failure.1 In addition to availability as pharmaceuticals, cardiac glycosides are also found in plants such as foxglove, oleander, red squill, and lily of the valley. Similar cardioactive steroids are also found in the skin of toads in the Bufonidae family and in some herbal medications. Despite declining use of digoxin, the prevalence of patients diagnosed with digoxin toxicity has remained constant, and the use of digoxin-specific antibody fragments has increased.2 Digitoxin, a cardiac glycoside similar in structure to digoxin but with a longer half-life, is no longer commercially available in the United States, but is available in Canada and elsewhere in the world.
Digoxin is a cardiac glycoside available for oral or intravenous use. Following oral absorption, digoxin reaches a maximal serum concentration 1 to 3 hours after ingestion. It is approximately 25% protein bound and has a large volume of distribution (6 to 7 L/kg). The drug is primarily eliminated through the kidneys.
Digoxin, like other cardiac glycosides, inhibits sodium-potassium ATPase.3 This inhibition results in increased intracellular sodium and increased extracellular potassium. As a result of the increased intracellular sodium, the sodium-calcium antiporter is not able to effectively remove calcium from the myocyte. Consequently, there is an increase in intracellular calcium, which augments inotropy. The increased intracellular calcium can contribute to delayed after-depolarizations, which may lead to premature ventricular contractions and dysrhythmias. In addition, there is a decreased refractory period of the myocardium, which increases automaticity and hence is associated with an increased risk of dysrhythmias. Furthermore, cardiac glycosides shorten atrial and ventricular repolarization, thereby decreasing the refractory period and thus increasing automaticity.
Cardiac glycosides also increase vagal tone via action at the carotid body, thereby reducing conduction through the sinoatrial and atrioventricular nodes. In toxic concentrations, cardiac glycosides can increase sympathetic tone. Digoxin can reduce plasma renin concentrations in patients with advanced heart failure, thereby resulting in peripheral vasodilation.4 In contrast, in those without heart failure, digoxin can cause vasoconstriction. This difference is likely due to increased sensitivity of the carotid baroreceptors in patients with advanced, chronic heart failure.5
Digoxin has a narrow therapeutic index, and toxicity results from an exaggeration of its pharmacologic activity. The timing and clinical presentation of acute versus chronic digoxin toxicity differ significantly (Table 193–1).6 In addition to cardiac manifestations such as syncope and dysrhythmia, digoxin toxicity may present with GI distress, dizziness, headache, weakness, malaise, delirium, or confusion. Thus, an elderly patient taking digoxin who presents with mental status changes should be evaluated for toxicity.
Clinical Presentation ...