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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 conduction
Retrograde 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
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
Open > inactivated
Very slow
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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
Open > inactivated
Very slow
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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, IV
Electrophysiological
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
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