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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