Digitalis Toxicity

Mechanism of Action and Indications

Digitalis refers to a class of cardioactive drugs called glycosides, which exert both mechanical and electrical effects on the heart. As noted, the most frequently used digitalis preparation is digoxin. (Digitoxin is rarely prescribed in the United States.)

The mechanical action of digitalis glycosides is to increase the strength of myocardial contraction (positive inotropic effect) in carefully selected patients with heart failure with reduced ejection fraction. The electrical effects relate primarily to decreasing automaticity and conductivity in the sinoatrial (SA) and atrioventricular (AV) nodes, in large part by increasing cardiac parasympathetic (vagal) tone. Consequently, digoxin is sometimes used to help control the ventricular response in atrial fibrillation (AF) and atrial flutter (see Chapter 15 ).

Because a number of more efficacious and safer medications have become available, along with ablation procedures, digoxin use is mostly limited to the patients with atrial fibrillation or flutter who cannot tolerate beta blockers (e.g., because of bronchospasm, constitutional side effects, hypotension) or certain calcium channel blockers (which may also cause hypotension and are contraindicated with heart failure). When used in AF or heart failure (HF), digoxin is most often employed adjunctively with other drugs. Occasionally, digoxin is still used in the treatment of certain reentrant types of paroxysmal supraventricular tachycardias (PSVTs), for example, during pregnancy when other drugs might be contraindicated.

Of particular importance for clinicians is the fact that digoxin has a relatively narrow therapeutic margin of safety. This term means that the difference (gradient) between clinically safe and toxic serum concentrations of digoxin is low.

Digitalis Toxicity vs. Digitalis effect

Confusion sometimes arises between the terms digitalis toxicity and digitalis effect . Digitalis toxicity refers to the arrhythmias and conduction disturbances, as well as the toxic systemic effects described later, produced by this class of drug. Digitalis effect ( Figs. 20.1 and 20.2 ) refers to the distinct scooping (sometimes called the “thumbprint” sign) of the ST-T complex, associated with shortening of the QT interval, typically seen in patients taking digitalis glycosides.

Digitalis Toxicity: Symptoms and Signs

Digitalis toxicity can produce a variety systemic symptoms, which may manifest before the emergence of specific arrhythmias and conduction disturbances. Common noncardiac symptoms include weakness, lethargy, anorexia, nausea, and vomiting. Rarely, visual effects with altered color perception, including yellowish vision (xanthopsia), and mental status changes may occur.

Although a wide range of ventricular and supraventricular arrhythmias may occur, certain tachy- and bradyarrhythmias are particularly suggestive of digoxin toxicity ( Box 20.1 ). One of the most common arrhythmic manifestations is increased ventricular ectopy with uniform or multiform premature ventricular premature complexes (PVCs; see Chapter 16 ) ( Fig. 20.3 ). Digoxin toxicity may also induce bidirectional ventricular tachycardia (VT) ( Fig. 20.4 ), a rare type of VT in which each successive beat in any lead alternates in direction. However, this rare arrhythmia may also be seen in the absence of digitalis excess (e.g., with catecholaminergic polymorphic VT; see 16, 21 ). Increasing toxicity, particularly with heart disease, may eventually lead to ventricular fibrillation and sudden cardiac arrest.