PHARMACOLOGY OF ANTI-ARRHYTHMICS

Arrhythmia (a-rhythm) means no rhythm,whereas dysrhythmia (dys-rhythm) means an abnormal heart rhythm. In practice,both terms are used interchangeably to mean an abnormal of irregular heart beat.

ArrhythmiaArrhythmia

Cardiac arrhythmias

25%

with digitalis

50% Aneathetized patients

over 80% with acute myocardial

infarction

Genesis of Normal

Heart Rhythm

Genesis of Tachyarrhythmia

Antiarrhythmic Drugs

ManagingTachyarrhythmias

Heart Rhythm

Genesis of Normal Heart Rhythm: The Myocardial Action Potential

(1) pacemaker activity

(2) absence of fast Na+ current in SA and AV nodes, where slow inward Ca2+ current initiates action potentials.

(3) long action potential ('plateau') and refractory period

(4) influx of Ca2+ during the plateau.

Electrophysiological Features

Phase-4 Depolarization results in automaticity of the cardiac action potential, in normal SA nodal cells.

The Effective Refractory The Effective Refractory Period(ERP)Period(ERP)

Genesis of Normal Heart Rhythm : Ion Channel

Genesis of Tachyarrhythmia

11 Classification of ArrhythmiasClassification of Arrhythmias

22 Enhanced AutomaticityEnhanced Automaticity

44 AfterpotentialsAfterpotentials

33 ReentryReentry

Classification of ArrhythmiasClassification of Arrhythmias

Bradyarrhythmias

Tachyarrhythmias

Unidirectional Block and Reentry

Late After DepolarizationLate After Depolarization

Sufficient Preparation

Depress resting membrane potential

Prolong Effective Refractory Period

Suppress enhanced automaticity

Slow conduction in tissue

Managing Tachyarrhythmias:

Strategies

Class IClass I Na+ Channel Blockers

Class IIClass II β-adrenergic Blockers

Class IIIClass III Prolong ERPClass IVClass IV Ca2+ Channel Blockers

Adenosine

Digoxin

Classification of Antiarrhythmic Classification of Antiarrhythmic Drugs (Vaughan-Williams)Drugs (Vaughan-Williams)

Classification of antiarrhythmic drugs

Class I:

Na+ Channel Blockers

Class I: Na+ Channel Blockers

Guinidine

Class II Antiarrhythmic Drugs:β1-adrenoceptor blockers

How Sympathetic Stimulation Increases Heart Rate and Accelerates Conduction:

Non-pacemaker Tissue:Sympathetic activity→Accelerated Conduction

Pacemaker:β- adrenoceptor stimulation:→ ↑ automaticity

Class II: β-adrenergic Blockers: Oppose effects of sympathetic tone

• Reduce automaticity (including physiological)

• Slow conduction• Mainly active in atrial & atrioventricu

lar tissue• Reduce risk of sudden death after he

art attack

Class II: Examples

• Propranolol• Metoprolol• many other -olol’s• Other aspects of pharmacology: loo

k up autonomic pharmacology notes

Class III:

Drugs that Prolong Action Potential Duration & ERP

Class III: Examples

• Amiodarone 胺碘酮• Sotalol 索他洛尔 (also β-block

er)

Class IV

Calcium Channel Blockers (also active in angina and

hypertension)

Adenosine

• Adenosine receptors on atrial myocardium and atrioventricular conducting tissue

• K+ channels are adenosine receptor-linked

Adenosine: Pharmacology

• Very rapid hydrolysis in blood – only IV use – rapid IV bolus

• For supraventricular tachycardias (may help diagnosis)

Effects of antidysrhythmic drugs on the dEffects of antidysrhythmic drugs on the different phases of the cardiac action poteifferent phases of the cardiac action potentialntial

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