Antiarrhythmic Drugs
Introduction of arrhythmia
i. Defination
When the rhythm of the heart become irregular, or the frequency of the atrial and ventricular beats
are different, too fast (tachycardia) or too slow (bradycardia), this is called an arrhythmia. An
arrhythmia is an abnormality in the heart's rhythm, or heartbeat frenquency.
ii. Classification
Bradycardia - a heart rate that is lower than normal(<60/min).
* Sinus bradycardia
* AV nodal blocks
Tachycardia -a heart rate that is higher than normal(>100/min)
Sinus tachycardia
Atrial tachycardia
Atrial flutter
Atrial fibrillation
Supraventricular tachycardia (SVT)
Ventricular premature beats (VPBs)
Ventricular tachycardia (VT)
Ventricular flutter
Ventricular fibrillation
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iii. Treatment
Many arrhythmias do not require any treatment. Some arrhythmias may need
treatment because rhythm that are too rapid, too slow can reduce cardiac output. Some
types of arrhythmias, such as ventricular tachycardia, are serious and even
life-threatening. Arrhythmias can be treated with drugs disscussed in this chapter or
with non-pharmacollogical therapies such as pacemaker, cardioversion, catheter
ablation, and surgery.
Section 1
Basis of Cardiac Electrophysiology
Important properties
Automaticity: The heart can excite itself without exogenous stimulus. The
automaticity results from Spontaneous depolarization in Phase 4 (slope of Phase 0).
Conductivity: The impulse can spread among cells. Conductivity is determined by
the rate and amplitude of Phase 0 depolarization.
APD & ERP: During phases 0, 1, 2, and part of phase 3, the cell is refractory to the
initiation of new action potentials. This is termed ERP (effective refractory period).
During the ERP, stimulation of the cell does not produce new, propagated action
potentials. The ERP acts as a protective mechanism in the heart by preventing
multiple, compounded action potentials from occurring. Many anti-arrhythmic drugs
prolong the ERP, thereby reducing cellular excitability. APD is action potential
duration, and its most important component is ERP.
Section 2 Mechanism of arrhythmias
Altered impulse formation
* Increased autorhythmicity
* Afterdepolarizations
Early afterdepolarizations (EAD)
Delayed afterdepolarizations (DAD)
Altered impulse conduction
* Reentry
Reentry requires three conditions coexisting:
 presence of a unidirectional block
 a anatomic or physiologic circuit
 critical timing. The conduction time must exceed the effective refractory period
Section 3 Mechenism of anti-arrythmic effect
Mechenism of antiarrythmic effect
* Reduce abnormal automaticity (phase 4 slope)
* Reduce afterdepolarization
•
decrease action potential duration
•
block sodium or calcium channel
* Abolish reentry--slow conduction further
a.↑conduction:↓unidirectional block
b.↓conduction : unidirectional block→ bidirectional block
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c.↑ERP
Section 4 Antiarrythmic Drugs
Class I---Na Channel Blocker
Class IA moderate potency
Class IB low potency
Class IC high potency
Class II ---β-blocker
Class III the drugs prolonging APD
Class IV---calcium channel blocker
A given drug may have multiple classes of action. For example, amiodarone shares all
four classes of action. Drugs are usually discussed according to the predominant class
of action. Certain antiarrhythmic agents, eg, adenosine, do not fit readily into this
scheme and are described separately.
Sodium Channel Blockers
1) ClassⅠA
a. Inhibit Na+ influx moderately :
↓the rate and amplitude of Phase 0 depolarization, ↓conduction
↓phase 4 slope, ↓autorhythmicity
b. ↓ K+ efflux, prolong the ERP
Quinidine(奎尼丁) –its use has decreased considerably in recent years.
Pharmacological Effects:
Cardiac Effects:
↓autorhythmicity;↓conduction;↑ERP;
↓myocardial contractility.
Extracardiac Effects:
α-adrenergic blocking and anticholinergic effect
Therapeutic Uses:
Broad-spectrum
 Atrial fibrillation; Atrial flutter;
 supraventricular tachycardia; ventricular tachycardia;
Toxicity:
Gastrointestinal side effects
Chichonic reaction(cinchonism）
CVS: Heart failure; hypotension; quinidine syncopy
2) Class IB
↓Na+ influx lightly
↑K+ efflux, shorten the APD>ERP, ERP/APD ↑
Lidocaine (利多卡因)
Pharmacological effects: Act on Purkinje fibers and ventricular cells
a.↓autorhythmicity;↓the slope of phase 4 and ↑the threshold for excitability.
b. Relative increase ERP: ERP/APD↑
Pharmacokinetics:
Therapeutic Use
Ventricular Tachycardia and Ventricular Fibrillation in
+
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•Myocardial infarction
•Digitalis intoxication
•Open-heart surgery
Phenytoin sodium: It has been used in the acute and chronic ventricular arrhythmias,
especially in digitalis intoxication.
Mexiletine is a congener of lidocaine that is resistant to first-pass hepatic metabolism
and is effective by the oral route. Its electrophysiologic and antiarrhythmic actions are
similar to those of lidocaine.
3) Class IC
Severely depress Na+ influx, markedly ↓conduction.
↓phase 4 slope. ↓ autorhythmicity
Serious adverse reactions are provocation of potentially lethal arrhythmias.
Propafenone: Block Na+ and Ca2+ channel, also blockβ-R
Used to treat Supraventricular and ventricular tachycardia; Supraventricular and
ventricular premature beat, Atrial fibrillation. The most common adverse effects are a
metallic taste and constipation; arrhythmia exacerbation can occur.
Class Ⅱ β-R Blockers
Propranolol
1) β-R blocking action
2) Membrane-stabilizing effect(↓Na+in)
Pharmacological effects:
a.↓autorhythmicity，↓afterdepolarization stimulated by CA, prevent triggered
activity.
b.↓ conduction of AV node and P-f ( >100ng/ml)
c.↑ERP of AV node,↓reentry
d. Improve myocardial ischemic
Therapeutic uses
Supraventricular arrhythmias; Acute myocardial infarction(AMI)
Class Ⅲ
Prolonging APD agents
+
+
Blocking K channel , ↓ K efflux , ↓ repolarization, ↑ APD and ERP
Amiodarone
Pharmacological effects: ↓K+, Na+, Ca2+ ions channel；Blocking α, β receptor
1) ↑APD and ERP, no reverse use-dependence
2) ↓autorhythmicity
3) ↓ conduction of AV node and Purkinje fibers
4) Dilate coronary artery, ↓ myocardial oxygen consumption
Pharmacokinetics: F: 35-60%, t1/2 25～60 d, last 4~12w
Therapeutic uses: Broad-spectrum antiarrhythmic drug
Life-threaten ventricular arrythmias; Artial fibrillation or atrial flutter;
superventricular tachycardia
Adverse effects:
CVS reactions: Sinus bradycardia, Atrial-ventricular block, long QT syndrome
(LQTS), hypotension.
Pulmonary fibrosis; Abnormal liver function; cornea deposits; skin deposits; Hypo- or
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hyperthyroidism
Sotalol : Nonselective β-R antagonist; Block Ik,↑APD、ERP; F=90%～100%;
Broad-spectrum antiarrhythmic drug.
Dofetilide: Blocking K+ channel (Ikr) selectivrly, ↓K+ efflux Delay repolarization,
APD and ERP↑
Dofetilide is approved for the maintenance of normal sinus rhythm in patients with
atrial fibrillation. It is also effective in restoring normal sinus rhythm in patients with
atrial fibrillation. Its main adverse effect is Tdp（2%～4%）.
Class IV: Calcium Channel Blockers
Verapamil
Pharmacological effects:
1. Reduction the automaticity of S-A node and ischemic myocardium
(↓afterdepolarization)
2. Slow AV Node Conduction
3. Prolong AV Node ERP
Therapeutic Use:
Supraventricular tachycardia arrythmias:
* Reentrant supraventricular (first choice)
* Atrial fibrilation and flutter ( reduce the ventricular rate)
Others Adenosine
Act on A-R, activate KACh ,↑K+ efflux, ↓Ca2+ influx, hyperpolarization and ↓
automaticity; Prolong AV Node ERP.
Choice for prompt conversion of paroxysmal supraventricular tachycardia.
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