Antiarrhythmic Drugs

Dr.U.P.Rathnakar
MD.DIH.PGDHM
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Myocardial cells are excitable! [Impulse generation, conduction & contraction]

SA Node Atria
Impulse generation [Pace maker] Conduction, contraction Conduction

AV Node HIS purkinje system Ventricles

Conduction

Conduction, contraction
2

Rhythmic Electrical and mechanical activity

27

Arrhythmias
What is normal cardiac rhythm? What is rhythm? Any activity in the universe occurring again and again at regular intervals Arrhythmia-abnormal rhythm
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Normal cardiac rhythm

Sinus tachycardia Rate-60-100 BPM

Impulse generation
Pace maker-Sinus

Atrial rhythm WPW syndrome Normal conduction pathways

Impulse propagation
Normal velocity First degree

HB

25

Types of arrhythmias
Bradyarrhythmias Tachyarrhythmias Supraventricular
Atrial fibrillation [AF] Atrial flutter [AFL] Paroxysmal supraventricular tachycardia [PSVT]

Ventricular
Ventricular fibrillation & Flutter [VF, VFL] Ventricular tachycardia [VT]
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Activities in the heart

Mechanical activity[contraction & CO]
Electrical activity [Imp.gen&cond.] Action potentials

Arrhythmias

Depolarization Repolarization Ionic fluxes

Anti arrhythmics

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Symp

Para Symp K K K

0
TP -40 RP -60

1 2 3

++++

3
TP -70

4
RP -90 Nodal tissue Myocyte

Cardiac action potential

21

Ca 3 0 4

Na

4 AP in pacemaker tissue

AP in non-pacemaker tissue

20

Pathogenesis of arrhythmias
Abnormalities of spontaneous automaticity Abnormalities of impulse generation Abnormalities of triggered automaticity

Impulse block Abnormalities of impulse propagation Re-entry phenomenon Anatomically defined Functionally defined

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Pathogenesis of arrhythmia
[Mechanisms of arrhythmias]

Triggered automaticity
[Abnormality of impulse generation]

Re-entry phenomenon [Circus movement]

[Abnormality of impulse conduction]

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Pathogenesis of arrhythmias
Abnormalities of impulse generation

Spontaneous automaticity

Abnormalities of triggered automaticity[ After depolarization]

Atrial and ventricular tachycardia Not common Acutely ill pts. Underlying disease+ Treat the cause

Early after depolarization[EADs] Delayed after depolarization[DADs]

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Pathogenesis of arrhythmias
Abnormalities of triggered automaticity Early after depolarization[EADs] K+ channels are defective-slow [QT prolongation]-Torse-De-Pontes

Drugs[K+ channel blockers] Hypokalemia

Low HR [Tt increase HR] 1, 2, 3 E A D

0 TP RMP

If Phase 4 [repolarization] is prolonged voltage gated [Na or Ca] channels 14 may be activated prematurely to produce EADs

Pathogenesis of arrhythmias
Abnormalities of triggered automaticity Delayed after depolarization [DADs] Adrenergic stress Digitalis toxicity Ischemia

1,

2, E A D

D A D

TP RMP

Fluctuations in baseline-due to Ca++ loading -If baseline comes near TP -DAD may occur

13

Pathogenesis of arrhythmias
Abnormalities of impulse propagation Impulse block[Heart blocks] Re-entry

AV blocks Beta blockers Calcium channel blockers Digitalis toxicity Adenosine Ischemia
12

Re-entry

11

Pathogenesis of arrhythmias
Re-entry phenomenon Anatomically defined Functionally defined

SAN

AVN

AV

1. 2. 3. 4.

2 pathways Nearly parallel Connected proximally and distally Different velocities & RP

10

Re-entry phenomenon
B A
1. Two roughly parallel conducting pathways must be present & 2. Connected proximally and distally by conducting tissue, forming a potential electrical circuit
Initiation of reentry

3. One pathway must have a longer refractory period

4. Pathway with the shorter refractory period must conduct electrical impulses more slowly than does the opposite pathway

An appropriately timed, premature electrical impulse can be blocked in pathway B (which has a relatively long refractory period) While conducting down pathway A. Because conduction down pathway A is slow, pathway B has time to recover, allowing the impulse to conduct retrogradely up pathway B. The impulse can then reenter pathway A. A continuously circulating impulse is thus 9 established.

Types of arrhythmias
Bradyarrhythmias Tachyarrhythmias Supraventricular
Atrial fibrillation [AF] Atrial flutter [AFL] Paroxysmal supraventricular tachycardia [PSVT]

Ventricular
Ventricular fibrillation & Flutter [VF, VFL] Ventricular tachycardia [VT]
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How do antiarrhythmics work?

Tachyarrhythmias mediated by changes in the cardiac action potential

Drugs that alter the action potential alter cardiac arrhythmias [By altering ionic fluxes]
8

How do antiarrhythmics work? Effect AP

Change the shape of the cardiac AP.

1. Conduction velocity [CV]. 2. Refractory period [RP] 3. Automaticity [AM]

Antiarrhythmic drugs do this by altering the channels that control the flow of ions across the cardiac cell membrane. 7

Antiarrhythmics Classification [Singh-Vaughan-Williams]

Sodium-channelBeta-blockers blockers
Pot.channel blockers Calcium channel blockers

Conduction Velocity

Refractory Period

Automaticity

How do antiarrhythmics work? Effect on AP

Increase RP[APD]

1. 2. 3. 4.

2 pathways Nearly parallel Connected proximally and distally Different velocities & RP

Decrease RP[APD]

Antiarrhythmics Classification [Singh-Vaughn-Williams]

Sodium-channelblockers
Procainamide ,CV-Moderately

Beta-blockers

Pot.channel blockers

Calcium channel blockers

Propranolol

Amiodarone Verapamil Diltiazem Sotalol

, CV-Mild

, CV-Profound

Miscellaneous Adenosine Magnesium Digitalis Atropine

Na+ Channel blockers

Class 1A
.Eg. Procainamide .CVRP .Atria & Ventricles .Oral & i.v. PK:Acetylation Uses:AF, Reentrant tachy,VT .ADEs: Anticholinergic SLE, agranulocytosis ProarrhythmicTorse-De-Pontes
Diisopyramide [-ve inotropic]

Class 1B
Eg.Lignocaine Na+ Channel No action at low HR User dependent APD[RP] Only ventricles i.v[bolus-infusion] Use: Vent.arrhythmias ADEs: CNS Proarrhythmic-rare

Class 1C
Eg. Porpafenone Conduction-V.potent Oral Beta blocker, -ve inotropic Uses: atrial & Vent.arrhythmias ADEs: Visual disturbances GIT effects Reserve drug

Mexiletine[O]

Flecanide [No beta blockade] 3

Class II-Betablockers
Eg.Propranolol
Mild, blunt arrhythmogenic effect SA Node-Phase 4 is blunted-reduces automaticity AV Node-slows conduction Protective-Prevents reentrant tachycardias Uses: Effective in arrhythmias where SA & AV nodes are involved AF & AFL-Reduces ventricular response Not effective in treating ventricular arrhythmias, but effectively protects.

Yes, last slide!