Dr. Rovina Ruslami SpPD Depart.

Of Pharmacology & Therapy Medical Faculty Padjadjaran University

Arrhythmia : asymptomatic
Antiarrhythmia

life threatening 2 goals :

Termination of an ongoing Arrhythmia Prevention of a recurrence

Control arrythmia Proarrhythmic effect

Cardiac cycle : automaticity

rhythmic AP

SA node

AV node

HIS-purkinje system

1 0 mV 0

-85 mV

4 eff refractory period

Action Potential

Mechanisms of Cardiac Arrhythmia

1. Enhanced automaticity / abnormal automaticity

2. Triggered automaticity 3. Block 4. Reentry

Tools
ECG DC-cardioversion ICDs (Implantable cardioverter defiblillators)

Mechanisms of AAD actions :

suppressing the initiating mechanism slow automaticity
1. phase 4 slope 2. threshold 3. max. diastolic potential 4. AP duration -blockers block of Na+, Ca++ adenosine block of K+

altering the reentrant circuit

altering the reentrant circuit

Normal

Undirectional block

Principles in the clinical use of AADs

Identify & remove precipitating factors Establish the goals of treatment
- some arrhythmias shouldnt be treated - symptoms due to arrhythmia - choosing among therapeutic approach

Minimize risks
- proarrhythmic effect - monitoring of plasma concentration - patient-specific contra indication

The electrophisiology of the heart as a moving target

Classification of AADs :
class
IA IB IC II

mechanism
Na+ channel blocker Na+ channel blocker Na+ channel blocker -adrenoceptor blocker

comment
slow phase 0 depol shorten phase 3 repol markedly slow phase 0 depol suppress phase 4 depol prolongs phase 3 repol shorten action potential

III
IV

K+

channel blocker

Ca++ channel blocker

Class I AADs
Na channel blocker slow phase 0 depol
excitability conductivity

Use-dependence

tachycardia

Class IA : bind to Na channel in intermediate speed

quinidine, procainamide, disopyramide

Class IB : bind rapidly to Na channel

lidocaine, mexiletine, tocainide

Class IC : bind slowly to Na channel

flecainide, propafenone

QUINIDINE
inhibits arrhythmia caused by hyperautomaticity Prevent reentry arrhythmia Indications : Wide variety of arrhythmia FK : p.o
Maintain SR after DC

A, AV, V - arrhythmia

Adverse effects : exacerbate arrhythmia--- block proarrhythmic effect CI : heart block, liver disease

PROCAINAMIDE
Analog of local anesthetic quinidine like effect Indications :
VT that non responsive to lidocaine

FK : p.o Adverse effects :

liver

kidney

inotropic negative, hypotension drug induced SLE (long-term therapy)

Intoxication : asystole, CNS depression

LIDOCAINE
Inhibits arrhythmia caused by abnormal automaticity rapidly bind to Na channel Indications :
Arrhythmia related to myocardial ischaemia

FK : iv

excretion : liver

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

CI : block, bradycardia

Class II AADs
-blocker slow phase 4 depol
automaticity HR & contractility AV conduction

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

Inotropic (-) CI for HF Propranolol, metoprolol, esmolol, carvedilol

Class III AADs

K channel blockers prolong phase 3
AP duration eff. Refractory period

sotalol, bretylium, amiodarone

SOTALOL
-blocker that has antiarrhythmia class III activity Proarrhythmic effect torsade de pointes

Indications : sustained VT, long-term :

mortality

BRETYLIUM
FK : iv excretion : kidney
Indications : life threatening VT , recurrent VF

AMIODARONE
Class I, II, III & IV action Indications : severe refractory SVT, VT FK : p.o, EMG case :iv (bolus drip)
clinical effect is achieved in 6 weeks (po)

mainly class III

Adverse effects :
vary toxicity effect, withdrawl effect liver toxicity, hyper-hypothyroidsm, muscle weakness CI : block, bradycardia

Class IV AADs
Ca channel blocker
HR & PR interval

shorten AP
AV conduction

Inotropic (-) CI for HF Vasodilator anti hypertension, anti anginal

Verapamil, diltiazem
Indication : tachy-arryhthmia: SVT, VT FK : p.o, iv ( !! hypotension) liver

DIGOXIN
Shorten refractory period; AP; conductivity

Indications : controll ventr respons to AF

FK : p.o; iv Adverse effects : intoxication : VES VT / VF

ADENOSIN
refractory period, conductivity, automaticity Indications : acute SVT FK : iv, short d.o.a Adverse effects : flushing, hypotension, chest pain