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INTRODUCTION

The medicinal benefits of cardiac glycosides have been recognized for centuries. Even with development of 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. Although intentional overdoses of cardiac glycosides are relatively uncommon, adverse drug reactions and chronic toxicity continue to cause morbidity.2,3

PATHOPHYSIOLOGY

Digoxin is a cardiac glycoside available for PO or IV 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 adenosine triphosphatase (ATPase).4 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 afterdepolarizations, which may lead to premature ventricular contractions and arrhythmias. In addition, there is a decreased refractory period of the myocardium, which increases automaticity and hence is associated with an increased risk of arrhythmias. 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.5 In patients with advanced heart failure, digoxin can cause vasoconstriction. However, in patients without heart failure, cardiac glycosides can cause vasoconstriction. This difference is likely due to increased sensitivity of the carotid baroreceptors in patients with advanced, chronic heart failure.6

CLINICAL FEATURES

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).7 In addition to cardiac manifestations such as syncope and arrhythmia, 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.

TABLE 193-1Clinical Presentation of Digitalis Glycoside Toxicity

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