59-291 Section 3, Lecture 4 Antiarrhytmic drugs cont… Pathophysiology of Arrhythmia Abnormal impulse formation Increased automaticity Afterdepolarization Abnormal impulse conduction Reentry in ventricular tissue Reentry in the AV node Drug-induced arrhythmia

Abnormal Impulse Conduction- Reentry: Most common mechanism of arrhythmias – re-excitation of cardiac tissue by the same impulse. -ischemia and tissue hypoxia results in a more negative resting potential and a decrease in membrane responsiveness Hypoxic tissue

As a result the conduction velocity slows down and ceases resulting in decremental conduction. The most common cause of unidirectional block in ventricular tissue. If block occurs in a bifurcated conduction pathway the conduction in one arm the anterograde conduction (normal direction) continues in one arm and travels through the retrograde (reverse direction) with full velocity jumping over the ischemic area.

Abnormal Impulse conduction Retrograde conduction of an impulse into previously depolarized tissue

Reentry into AV node- most common electrophysiological event responsible for paroxysmal supra-venticular tachychardia (PSVT). Note: not due to decremental conduction but due to differences in the refractory periods in the two pathways

Classification of Anti-arrhythmic drugs Class I- Na+-channel blockers- Class II- -adrenergic antagonists Class III- K+-channel blockers Class IV- Ca2+-channel blockers Class I- Na+-channel blockers- bind to Na+-channels in the open and inactivated states not to the resting state –reduce abnormal automaticity

Electrophysiologic properties of sodium channel blockers Drugs dissociate from the sodium channels at different rates (recovery). Drugs with a slow recovery have a greater effect on cardiac conduction velocity Drug Class Example Sodium Channel Affinity Rate of Dissociation Class IA Quinidine Open > inactivated Slow Class IB Lidocaine Inactivated > open Rapid Class IC Flecainide Very slow

Electrophysiological effects Drug Class Example Sodium Channel Affinity Rate of Dissociation Class IA Quinidine Open > inactivated Slow Class IB (Affect ischemic tissues) Lidocaine Inactivated > open Rapid Class IC (Affect ventricular conduction) Flecainide Very slow

IA- Quinidine- oral, absorbed adequately through gut Adverse effects- diarrhea in 30% of patients; syncope second to reduction in CO and BP; higher doses cause tinnitus, dizziness, blurred vision Indications- -increases AV node conduction velocity and ventricular rate in patients with atrial fibrillation. These patients should be given digoxin which lowers AV node conduction velocity IB- Lidocaine- IV administered as a bolus then followed by continuous IV -used in the treatment of Ventricular Tachycardia and other acute arrhythmias Adverse effects- CNS effects including nervousness, tremor, may also slow conduction in normal ventricular tissue. Drug interaction with cimetidine (P450 inhibitor) elevates lidocaine Cp.

Class II- used as inhibitors of supraventicular arrhythmias -adrenergic antagonists block Symp. activation of cardiac automaticity and conduction Class II, IV Electrophysiological effects

Class II – Esmolol delivered by IV short half-life, ideally suited for acute supraventicular tachycardia. Side effects and indications same as other beta-blockers Class III-prolong ventricular action potential duration and the refractory period.

Class IV- Ca2+-channel blockers- decrease AV node conduction velocity and increase AV node refractory period Diltiazem and Verapamil- given via IV to terminate acute supraventicular tachycardia and to reduce ventricular rate in patients with atrial fibrillation;

Practice Question All of the following antiarrythmic drugs increase QT duration except: Class IA Class IB Class IC Class III

Verapamile is classified in _________ and it _______ to exert its antiarrythmic effects. Class IA, increases PP duration Class IB, increase QT duration ClassIC, increase QRS duration Class IV, increase PP duration