Which of the following antiarrhythmic drugs may be more likely to have proarrhythmia at increased heart rates?
Flecainide. Flecainide is a class IC antiarrhythmic drug, and these agents exhibit “use dependence.” This refers to the property of increased drug effect at increased heart rates. Sotalol and dofetilide are class III antiarrhythmic drugs that exhibit “reverse-use dependence”—that is, greater drug effect at slower heart rates. Quinidine has effects on both sodium and potassium channels. While the effects on the sodium channels are use dependent, it is far less pronounced compared with the Ic agents such as flecainide. The potassium-blocking properties and resulting QT prolongation are more pronounced at slower heart rates— reverse-use dependent.
Which of the following statements is true regarding antiarrhythmic drugs with reverse-use dependence?
Antiarrhythmic drugs with reverse-use dependence have greater efficacy for arrhythmia prevention than termination and have greater risk for ventricular proarrhythmia after AFib termination (at slower sinus rates) than during AFib. Antiarrhythmic drugs with use dependence, such as sotalol and dofetilide, have greater antiarrhythmic effect at slower heart rates. Consequently, drug efficacy is enhanced at the relatively slower rates in sinus rhythm, making these drugs more effective for prevention of AFib than those drugs with use dependence. Likewise, for proarrhythmia, the antiarrhythmic drugs with reverse-use dependence are more likely to produce ventricular proarrhythmia after conversion to sinus rhythm at the relatively slower sinus rate or with a postconversion pause.
Which of the following is true regarding the Cardiac Arrhythmia Suppression Trials (CAST I and II)?
The treatment drugs effectively suppressed premature ventricular complexes (PVCs). CAST studied the concept that PVC suppression in the postinfarction period would reduce the incidence of sudden cardiac death. Patients without heart disease were, therefore, excluded from these studies. CAST I studied flecainide, encainide, and moricizine versus placebo. Demonstration of effective suppression of PVCs by one of the drugs was necessary before a patient could be randomized to drug or placebo treatment. Propafenone, another class IC antiarrhythmic drug, was not studied. CAST I was prematurely terminated by the safety committee after only a 10-month average follow-up because of significantly increased incidence of arrhythmic death and nonfatal cardiac arrests in the flecainide and encainide treatment groups. CAST II was a continuation of the study with only moricizine versus placebo, but this study was also terminated early because of an increased incidence of cardiac arrest in the moricizine treatment group.
Which of the following antiarrhythmic drugs is the most potent sodium channel blocker?
Flecainide. All of these drugs are class I antiarrhythmic medications and have sodium channel–blocking properties to various degrees. Class IC agents, such as flecainide, have the most potent sodium channel–blocking effects, and class IB agents, such as lidocaine, have the least potent sodium channel–blocking effects.
Which of the following effects is expected when administering adenosine to a patient with recent cardiac transplantation (denervated heart)?
Enhanced effect. Patients with denervated hearts are supersensitive to the effects of adenosine.
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