A 44-year-old man reports exertional shortness of breath and palpitations. On examination, he has a systolic murmur at the left sternal border and cardiac apex, which gets louder when he stands up. He is diagnosed with obstructive hypertrophic cardiomyopathy and paroxysmal atrial fibrillation, and is started on a medication. Changes in the action potential of ventricular muscle cells before and after administration of medication are shown in the image below Black curve = Before administration of medication
Red curve = After administration of medicationThe patient is most likely being treated with which of the following medications?

Question

A 44-year-old man reports exertional shortness of breath and palpitations.  On examination, he has a systolic murmur at the left sternal border and cardiac apex, which gets louder when he stands up.  He is diagnosed with obstructive hypertrophic cardiomyopathy and paroxysmal atrial fibrillation, and is started on a medication.  Changes in the action potential of ventricular muscle cells before and after administration of medication are shown in the image below  Black curve = Before administration of medication
Red curve = After administration of medicationThe patient is most likely being treated with which of the following medications?

Quizplus · Accepted Answer

11ec160b_3b7c_8423_9249_4b0317231a76_MD0001_00 The illustration shows predominant slowing of phase 0 depolarization and prolongation of phase 3 repolarization (red curve) of ventricular action potential after administration of the drug. This action is usually seen with the use of class IA antiarrhythmics drugs (quinidine, procainamide, and disopyramide). Class I antiarrhythmic drugs block sodium channels and inhibit initial phase 0 depolarization of action potential, thereby slowing conduction. Class IA agents also have moderate potassium channel-blocking activity, leading to a slow rate of repolarization and prolongation of action potential duration in the cardiac myocytes. (Choice A) Adenosine activates potassium channels and increases potassium conductance by interacting with A1 receptors on the surface of cardiac cells. This causes membrane hyperpolarization, resulting in transient slowing of the sinus rate and an increase in atrioventricular (AV) nodal conduction delay. Adenosine does not modulate the ventricular myocyte action potential. (Choice B) Digoxin exerts its antiarrhythmic effects by increasing vagal output to the AV node and conduction system, thereby slowing conduction in these tissues. It does not alter the ventricular myocyte action potential, but it does increase intracellular calcium in ventricular myocytes, leading to increased cardiac contractility. (Choice C) Calcium channel blockers are class IV antiarrhythmic drugs (eg, verapamil, diltiazem) that inhibit L-type calcium channels, slowing depolarization in the sinoatrial and AV nodes and decreasing calcium entry into cardiomyocytes. Calcium channel blockers slow the sinus rate, prolong AV node conduction, and depress myocardial contractility. (Choice E) Flecainide is a class IC antiarrhythmic that strongly blocks sodium channels. It exhibits a slow rate of receptor dissociation that makes it more effective at higher rates of depolarization (use dependence). Class IC drugs slow phase 0 depolarization but do not affect action potential duration. (Choice F) Lidocaine is a class IB antiarrhythmic drug that has weak sodium channel-blocking activity at rest; however, it is quite effective in blocking sodium channels in depolarized cardiac myocytes. Class IB drugs also shorten phase 3 repolarization (blockade of "plateau" Na+ current), thereby decreasing action potential duration. (Choice G) Propranolol is a beta-adrenergic blocking agent that slows conduction through the AV node and prolongs phase 4 depolarization in cardiac pacemaker cells. Beta blockers do not affect ventricular myocyte action potential; their primary site of action is on the AV node and cells with automaticity. Educational objective: The class IA antiarrhythmics (quinidine, procainamide, and disopyramide) are sodium channel-blocking agents that depress phase 0 depolarization. They also prolong repolarization due to moderate potassium channel- blocking activity, increasing action potential duration in cardiac myocytes.

A 44-Year-Old Man Reports Exertional Shortness of Breath and Palpitations