Chapter 87: Antiarrhythmic Drugs
All of the following are sodium channel blockers except:
The answer is D. (Hurst’s The Heart, 14th Edition, Chap. 87) d,l-Sotalol is a racemate of d and l isomers, and it is a Vaughan-Williams class III antiarrhythmic drug that blocks potassium channels, specifically the rapidly activated component of the delayed rectifier outward potassium current (IKr).1 In addition, the l isomer also exhibits nonselective beta-blocking activity. Electrophysiologic effects of sotalol include an increase in action potential duration in both the atria and ventricles and a decrease in sinus rate and AV conduction. Flecainide (option A) is a sodium channel blocker (class Ic antiarrhythmic drug), which specifically blocks the channel in its open state with slow recovery from block. Procainamide (option B), disopyramide (option C), and quinidine (option E) are all Vaughan-Williams class Ia antiarrhythmic drugs. These block the sodium channel in its open state, with an intermediate recovery from block. They also inhibit IKr at relatively lower concentrations. There is moderate phase 0 depression and conduction slowing with prolongation of the action potential. Lidocaine and mexiletine are both examples of class Ib antiarrhythmic drugs that block the sodium channel in its inactivated state.
You are seeing a 50-year-old man in the emergency department for new-onset atrial fibrillation (AF). The patient’s palpitations started 2 hours ago. The emergency room doctor has already given a dose of intravenous metoprolol, which has resulted in minimal slowing of the ventricular rate. You decide to give oral propafenone due to its marked increase in sodium channel blockade during tachycardia. This specific characteristic of class Ic antiarrhythmics is known as:
A. Reverse use dependence
The answer is B. (Hurst’s The Heart, 14th Edition, Chap. 87) The class Ic drugs (flecainide and propafenone) dissociate from the sodium channels in the resting state very slowly, exhibiting strong use dependence that manifests as a marked increase in sodium channel blockade during tachycardia. This is thought to be responsible for the increased efficacy of the class Ic antiarrhythmic drugs in slowing and converting tachycardia with minimal effects at normal sinus rates. However, strong use dependence of a drug on INa may be proarrhythmic (eg, flecainide-induced atrial flutter or VT) when the effect of the drug on conduction slowing is stronger ...