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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

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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

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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.

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Abnormal Impulse conductionRetrograde conduction of an impulse into previously depolarized tissue

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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

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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

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Electrophysiologic properties of sodium channel blockers

Drug Class Example Sodium Channel AffinityRate of Dissociation

Class IA Quinidine Open > inactivated Slow

Class IB Lidocaine Inactivated > open Rapid

Class IC Flecainide Open > inactivated Very slow

Drugs dissociate from the sodium channels at different rates (recovery). Drugs with a slow recovery have a greater effect on cardiac conduction velocity

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Drug Class ExampleSodium 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 Open > inactivated Very slow

Electrophysiological effects

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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.

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Class II- used as inhibitors of supraventicular arrhythmias -adrenergic antagonists block Symp. activation of cardiac automaticity and conduction

Class II, IVElectrophysiological effects

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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.

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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;

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Practice Question• All of the following antiarrythmic drugs

increase QT duration except:

• Class IA

• Class IB

• Class IC

• Class III

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• 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