Digoxin is commonly used for the treatment of atrial fibrillation, especially with co-existing congestive heart failure. Cardiac glycosides, including digoxin, inhibit the sodium-potassium-ATPase, resulting in increased intracellular sodium and increased extracellular potassium. The increased intracellular sodium ultimately results in increased intracellular calcium and increased inotropy. The excessive intracellular calcium can result in delayed after-depolarizations, which may result in premature contractions and dysrhythmias.

Digoxin toxicity can occur in the acute or chronic setting. Acute toxicity is more likely to result in a younger individual following an acute overdose. Nausea, vomiting, hyperkalemia, and dysrhythmias are common. Chronic digoxin toxicity frequently occurs in the elderly as a result of decreased clearance of digoxin, due to either declining renal function or drug-drug interactions. Nausea, malaise, and weakness are common findings in chronic digoxin toxicity.

Acute digoxin toxicity differs significantly from chronic digoxin toxicity Acute digoxin toxicity is likely to cause gastrointestinal symptoms, such as anorexia, nausea, vomiting, and abdominal pain. Visual changes, including alteration in the color vision, are well described. Hyperkalemia is commonly observed, and is prognostic (see below).

Chronic toxicity, in contrast, is harder to diagnose, and has a more insidious onset of symptoms. The gastrointestinal symptoms can be less pronounced than in acute toxicity. Neurologic manifestations, such as lethargy, fatigue, confusion, and weakness, are common. Hyperkalemia or hypokalemia can be observed.

Diagnosis

The diagnosis of digoxin toxicity is primarily a clinical diagnosis based on symptoms, as well as the electrocardiogram and potassium. Digoxin levels can be obtained, but should not be the sole basis for determining digoxin toxicity.Because of the narrow therapeutic index of digoxin, patients can be digoxin toxic with therapeutic digoxin concentrations. Furthermore, an elevated digoxin concentration does not translate to digoxin toxicity.
Various other cardiac glycosides, including plants (e.g., oleander, lily of the valley, etc.) can cause cardiac glycoside toxicity. In these patients, a detectable digoxin concentration can help confirm the diagnosis, but because the assay is designed specifically to measure digoxin, interpretation of the absolute value of the level is not helpful, and the level can be used only to confirm exposure, not assess degree of exposure.Free digoxin concentrations can be obtained to help differentiate between endogenous digoxin-like substances, as well as measuring circulating digoxin concentrations after antidotal therapy
The constellation of gastrointestinal symptoms, along with hyperkalemia and an electrocardiogram demonstrating AV blocks, bradycardia, or ventricular dysrhythmias, along with a digoxin concentration in the upper limit of normal or elevated digoxin concentration should make the clinician suspect acute digoxin toxicity

The finding of weakness and malaise, especially in an elderly patient with impaired renal function, who is on digoxin should make the clinician suspect chronic digoxin toxicity.Hyperkalemia is most often observed with renal failure or exogenously administered potassium. Other medications can occasionally cause hyperkalemia, as could some endocrine disturbances.

Specific Treatment

The first priority in treatment is ensuring the patient has an adequate airway and breathing. Patients who are bradycardic can receive atropine 0.5 mg IV, although any response is likely to be transient and minimal.
Patients should be assessed for the administration of digoxin-specific Fab fragments (antibodies). Those patients who are hyperkalemic or have life-threatening dysrhythmias should receive digoxin immune Fab fragments.
Cardiac glycoside-induced hyperkalemia should be treated with digoxin-specific Fab fragments. These antibodies will effectively reduce the hyperkalemia due to cardiac glycosides. Patients with underlying renal dysfuntion who are hyperkalemic from their underlying renal failure, however, may need traditional treatments for hyperkalemia. However, if the hyperkalemia is thought to be due to a cardiac glycoside, including digoxin, the primary treatment is simply the digoxin-specific antibodies.

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Toxicology: Open Access