Drug Effects and Electrolyte Disorders

Antiarrhythmic drugs

By several mechanisms, some drugs, particularly antiarrhythmic drugs, can cause serious rhythm disturbances in susceptible individuals. This is termed proarrhythmia . Proarrhythmia encompasses an extensive list of arrhythmia types, including increase in premature ventricular contractions (PVCs), nonsustained ventricular tachycardia, sustained monomorphic ventricular tachycardia, polymorphic ventricular tachycardia, and ventricular fibrillation. Some drugs increase the risk of bradycardia or atrioventricular (AV) block, another form of proarrhythmia.

Antiarrhythmic drugs that block sodium channels (class I drugs, including procainamide, quinidine, disopyramide, flecainide, and propafenone) prolong conduction in atrial and ventricular muscle and in the His Purkinje system. By so doing, they can cause QRS widening, AV block or monomorphic and/or polymorphic ventricular tachycardia in susceptible patients. Slowing of conduction in the atrium in patients treated for atrial fibrillation (AF) can result in organization to atrial flutter, which can be slow (< 200 bpm) and conduct 1:1 through the atrioventricular node (AVN) at a paradoxically faster rate than typical faster (300 bpm) atrial flutter, which typically conducts through the AVN in 2:1 fashion at 150 bpm due to AV nodal refractoriness. The atrial proarrhythmia can occur with a narrow QRS complex or with a wide complex QRS due to concomitant slowing of conduction in the ventricles. At very high (toxic doses) of IC antiarrhythmic drugs, the electrocardiogram (ECG) can look like hyperkalemia or ventricular tachycardia.

Drugs that prolong repolarization (class IA antiarrhythmic drugs, such as procainamide and quinidine, and class III antiarrhythmic drugs, such as sotalol, dofetilide, and occasionally amiodarone) generally block the I _Kr channel, which can induce an acquired form of long QT syndrome (LQTS). Many noncardiac drugs can also prolong repolarization, prolong the QT interval, and predispose to torsades de pointes ventricular tachycardia (TdP VT) because of their effects on the I _Kr channel, the rapid component of the delayed rectifying potassium current. A partial list of drugs that prolong QT is provided in Table 6.2 , and the reader is referred to the website https://www.crediblemeds.org for a more inclusive and up-to-date list of offending drugs. The most catastrophic effect of QT prolongation is the development of TdP with cardiac arrest and sudden death.

Antiarrhythmic drugs (class IC drugs, sotalol and amiodarone, in particular) can affect the sinus node and cause sinus bradycardia in susceptible patients.

Digitalis toxicity

Digitalis is used in the treatment of systolic heart failure and for ventricular rate control in AF. Digitalis has effects on the ECG, including depression of the PR and sagging of the ST segments, decrease in T-wave amplitude, shortening of the QT interval, and increase in U-wave amplitude. The therapeutic level of digitalis is typically 0.7 to 2.0 ng/mL, although toxicity can occur within this range, and worse survival has been associated with levels less than 0.9 ng/mL. Digitalis toxicity can be exacerbated by hypokalemia, hypomagnesemia, hypercalcemia, hypoxemia, hypothyroidism, renal insufficiency, and volume depletion. Drugs that interact with digitalis, that raise serum digitalis levels, and that could contribute to digitalis toxicity include certain antibiotics (e.g., tetracycline and erythromycin) and antiarrhythmics (quinidine, flecainide, amiodarone, and verapamil). Digitalis toxicity can lead to systemic symptoms, such as gastrointestinal symptoms (nausea, vomiting, diarrhea, anorexia), central nervous system abnormalities (headache, lethargy, seizures), and visual changes (scotoma, halos, color perception changes). In addition, digitalis toxicity can cause a wide range of arrhythmias and conduction disturbances. Some of the common digitalis toxicity rhythms include the following:

• Sinus bradycardia (see Fig. 1.4 )

• Sinus pause (see Fig. 1.9 )

• Mobitz type I second-degree AV block (see Fig. 2.3 )

• High-grade AV block (see Fig. 2.8 )

• Complete AV block (complete heart block [CHB]) with junctional or ventricular escape rhythms (see Fig. 2.12 )

• Premature ventricular complexes (see Fig. 3.6 )

• Accelerated junctional rhythm (see Fig. 3.15 )

• Junctional tachycardia (JT) (see Fig. 5.23 )

• Ventricular fibrillation (VF) (see Fig. 6.8 or 6.9 )

• Ventricular tachycardia (VT) (see Fig. 4.2 or 6.2 )

• Other rhythms that are associated more with digitalis toxicity than with other circumstances (although none are pathognomonic of digitalis toxicity) include the following:

  • AF with regular ventricular response (indicating CHB) ( Fig. 9.1 )

    

  • Atrial tachycardia (AT) with AV block, usually 2:1 ( Fig. 9.2 )

    

  • Fascicular tachycardia ( Fig. 9.3 )

    

  • Bidirectional tachycardia ( Fig. 9.4 )