Depart. Of Pharmacology & TherapyMedical Faculty – Padjadjaran University

ROVINA RUSLAMI ROVINA RUSLAMI

Antiarrhythmia 2 goals :Antiarrhythmia 2 goals :

Arrhythmia : asymptomatic life threatening

Arrhythmia : asymptomatic life threatening

Termination of an ongoing ArrhythmiaTermination of an ongoing ArrhythmiaPrevention of a recurrencePrevention of a recurrence

Control arrythmiaControl arrythmia

Proarrhythmic effectProarrhythmic effect

Cardiac cycle : automaticity rhythmic APCardiac cycle : automaticity rhythmic AP

SA node AV node HIS-purkinje system

0

2

0 mV

-85 mV

3

1

4

eff refractory period

Action Potential Action Potential

Mechanisms of Cardiac ArrhythmiaMechanisms of Cardiac Arrhythmia

1. Enhanced automaticity / abnormal automaticity1. Enhanced automaticity / abnormal automaticity

2. Triggered automaticity2. Triggered automaticity

3. Block3. Block4. Reentry4. Reentry

ToolsTools

ECG ECG

DC-cardioversion DC-cardioversion

ICDs (Implantable cardioverter defiblillators) ICDs (Implantable cardioverter defiblillators)

Mechanisms of AAD actions :Mechanisms of AAD actions :

suppressing the initiating mechanism

slow automaticity

suppressing the initiating mechanism

slow automaticity

altering the reentrant circuit altering the reentrant circuit

1. phase 4 slope

2. threshold

3. max. diastolic potential

4. AP duration

1. phase 4 slope

2. threshold

3. max. diastolic potential

4. AP duration

β-blockers

block of Na+, Ca++

adenosine

block of K+

β-blockers

block of Na+, Ca++

adenosine

block of K+

Normal Undirectional block

altering the reentrant circuit altering the reentrant circuit

Principles in the clinical use of AADsPrinciples in the clinical use of AADs

Identify & remove precipitating factorsIdentify & remove precipitating factors

Establish the goals of treatmentEstablish the goals of treatment

- some arrhythmias shouldn’t be treated- some arrhythmias shouldn’t be treated

- symptoms due to arrhythmia- symptoms due to arrhythmia

- choosing among therapeutic approach- choosing among therapeutic approach

Minimize risksMinimize risks

- proarrhythmic effect- proarrhythmic effect

- monitoring of plasma concentration- monitoring of plasma concentration

- patient-specific contra indication- patient-specific contra indication

The electrophisiology of the heart as a “moving target”The electrophisiology of the heart as a “moving target”

IA Na+ channel blocker

IB Na+ channel blocker

IC Na+ channel blocker

II β-adrenoceptor blocker

III K+ channel blocker

IV Ca++ channel blocker

Classification of AADs :Classification of AADs :

classclass mechanism

mechanism commentcomment

slow phase 0 depol

shorten phase 3 repol

markedly slow phase 0 depol

suppress phase 4 depol

prolongs phase 3 repol

shorten action potential

Class I AADsClass I AADs

Na channel blocker slow phase 0 depolNa channel blocker slow phase 0 depol

excitabilityexcitability

conductivityconductivity

Use-dependence tachycardiaUse-dependence tachycardia

Class IA : bind to Na channel in intermediate speed quinidine, procainamide, disopyramide

Class IA : bind to Na channel in intermediate speed quinidine, procainamide, disopyramide

Class IB : bind rapidly to Na channel lidocaine, mexiletine, tocainide

Class IB : bind rapidly to Na channel lidocaine, mexiletine, tocainide

Class IC : bind slowly to Na channel flecainide, propafenone

Class IC : bind slowly to Na channel flecainide, propafenone

QUINIDINEQUINIDINE

inhibits arrhythmia caused by hyperautomaticityPrevent reentry arrhythmia

inhibits arrhythmia caused by hyperautomaticityPrevent reentry arrhythmia

Indications :Indications :

Wide variety of arrhythmiaWide variety of arrhythmia A, AV, V - arrhythmia A, AV, V - arrhythmia

Maintain SR after DC Maintain SR after DCFK :FK : p.op.o

Adverse effects : exacerbate arrhythmia--- blockproarrhythmic effect

Adverse effects : exacerbate arrhythmia--- blockproarrhythmic effect

CI : heart block, liver diseaseCI : heart block, liver disease

PROCAINAMIDEPROCAINAMIDE

Analog of local anestheticAnalog of local anesthetic

Indications :Indications :

VT that non responsive to lidocaineVT that non responsive to lidocaine

FK :FK : p.o liver kidneyp.o liver kidney

Adverse effects : inotropic negative, hypotensiondrug induced SLE (long-term therapy)

Adverse effects : inotropic negative, hypotensiondrug induced SLE (long-term therapy)

Intoxication : asystole, CNS depressionIntoxication : asystole, CNS depression

quinidine like effect quinidine like effect

LIDOCAINELIDOCAINE

Inhibits arrhythmia caused by abnormal automaticityInhibits arrhythmia caused by abnormal automaticity

Indications :Indications :

Arrhythmia related to myocardial ischaemiaArrhythmia related to myocardial ischaemia

FK :FK : iv excretion : liveriv excretion : liver

Adverse effects : inotropic negative (-); CNS effects, tremor proarrhythmic effects

Adverse effects : inotropic negative (-); CNS effects, tremor proarrhythmic effects

CI : block, bradycardiaCI : block, bradycardia

rapidly bind to Na channel rapidly bind to Na channel

β-blocker slow phase 4 depolβ-blocker slow phase 4 depol

Class II AADsClass II AADs

automaticityautomaticity

AV conduction AV conduction

Arrhythmia due to :- sympathetic activity- AF, SVT- post AMI prevent suddent death

Arrhythmia due to :- sympathetic activity- AF, SVT- post AMI prevent suddent death

Inotropic (-) CI for HFInotropic (-) CI for HF

HR & contractility HR & contractility

Propranolol, metoprolol, esmolol, carvedilolPropranolol, metoprolol, esmolol, carvedilol

K channel blockers prolong phase 3K channel blockers prolong phase 3

Class III AADsClass III AADs

AP durationAP duration

eff. Refractory period eff. Refractory period

sotalol, bretylium, amiodaronesotalol, bretylium, amiodarone

SOTALOLSOTALOL

β-blocker that has antiarrhythmia class III activityβ-blocker that has antiarrhythmia class III activity

Indications : sustained VT, long-term : mortalityIndications : sustained VT, long-term : mortality

Proarrhythmic effect torsade de pointesProarrhythmic effect torsade de pointes

iv excretion : kidneyiv excretion : kidney

BRETYLIUMBRETYLIUM

Indications : life threatening VT , recurrent VFIndications : life threatening VT , recurrent VF

FK :FK :

AMIODARONEAMIODARONE

Indications : severe refractory SVT, VTIndications : severe refractory SVT, VT

Class I, II, III & IV action mainly class IIIClass I, II, III & IV action mainly class III

FK :FK : p.o, EMG case :iv (bolus drip)clinical effect is achieved in 6 weeks (po)

p.o, EMG case :iv (bolus drip)clinical effect is achieved in 6 weeks (po)

Adverse effects : vary toxicity effect, withdrawl effectliver toxicity, hyper-hypothyroidsm, muscle weakness

Adverse effects : vary toxicity effect, withdrawl effectliver toxicity, hyper-hypothyroidsm, muscle weakness

Ca channel blocker shorten APCa channel blocker shorten AP

Class IV AADsClass IV AADs

AV conduction AV conduction

Inotropic (-) CI for HFInotropic (-) CI for HF

HR & PR interval HR & PR interval

Verapamil, diltiazemVerapamil, diltiazem

Vasodilator anti hypertension, anti anginalVasodilator anti hypertension, anti anginal

Indication : tachy-arrhthmia: SVT, VTIndication : tachy-arrhthmia: SVT, VT

FK : p.o, iv ( !! hypotension) liverFK : p.o, iv ( !! hypotension) liver

refractory period, conductivity, automaticity refractory period, conductivity, automaticity

Shorten refractory period; AP; conductivityShorten refractory period; AP; conductivity

Indications : controll ventr respons to AFIndications : controll ventr respons to AF

FK :FK : p.o; iv p.o; iv

Adverse effects : intoxication : VES VT / VFAdverse effects : intoxication : VES VT / VF

DIGOXINDIGOXIN

Indications : acute SVTIndications : acute SVT

FK :FK : iv, short d.o.a iv, short d.o.a Adverse effects : flushing, hypotension, chest painAdverse effects : flushing, hypotension, chest pain

ADENOSINADENOSIN