Obat Antiarritmia

Fathiyah Safithri

Laboratorium Farmakologi Fakultas Kedokteran UMM

Arritmia
Kondisi jantung dimana terjadi gangguan pada
Pembentukan impuls oleh ‘pacemaker’
Konduksi impuls kontraksi
Kombinasi keduanya
Yang menyebabkan gangguan kecepatan
dan/atau waktu kontraksi otot jantung shg tidak
mampu mempertahankan curah jantung (COP)
yang normal
Normal heartbeat and atrial arrhythmia

Normal rhythm Atrial arrhythmia

AV septum
Electrophysiology - resting potential

A transmembrane electrical gradient (potential) is

maintained, with the interior of the cell negative
with respect to outside the cell

Caused by unequal distribution of ions inside vs.

outside cell
Na+ higher outside than inside cell
Ca+ much higher “ “ “ “
K+ higher inside cell than outside

Maintenance by ion selective channels, active

pumps and exchangers
 Contraction of
ECG (EKG) showing wave ventricles
segments

Repolarization of
Contraction
ventricles
of atria
 Cardiac Action Potential
Aksi potensial bisa tjd pd :
- Conducting tissue (SA node, AV node) – selalu ada depolarisasi
bertahap s.d threshold – muncul spike (peran Ca 2+)
- Non conducting tissue(atrium, ventrikel) – butuh impuls dr
conducting tissue-depolarisasi s.d spike (diawali peran Na+)
Divided into five phases (0,1,2,3,4)
Phase 4 - resting phase (resting membrane potential)
Phase cardiac cells remain in until stimulated
Associated with diastole portion of heart cycle
Addition of current into cardiac muscle (stimulation) causes
Phase 0 – opening of fast Na channels and rapid
depolarization
Drives Na+ into cell (inward current), changing
membrane potential
Transient outward current due to movement of Cl- and K+
Phase 1 – initial rapid repolarization
Closure of the fast Na+ channels
Phase 0 and 1 together correspond to the R and S
waves of the ECG
Cardiac Action Potential (con’t)
Phase 2 - plateau phase
Opening of slow Ca2+ channel
sustained by the balance between the inward movement of Ca+ and
outward movement of K +
Corresponds to ST segment of the ECG.

Phase 3 – repolarization
Due to closure of the Ca2+ and K+ channels remain open, causing
a massive loss of K+ out off the cell
Allows K+ to build up outside the cell, causing the cell to repolarize
K + channels finally close when membrane potential reaches certain
level
Corresponds to T wave on the ECG
Mechanisms of Cardiac Arrhythmias

Result from disorders of impulse

formation, conduction, or both

Causes of arrhythmias
Cardiac ischemia  increased Ca2+
entry
Excessive discharge or sensitivity to
autonomic transmitters , stimulation R/
β1 increased Ca2+ entry
Increased Na+ entry  depolarisation
Obat antiarritmia
Group IA
Cause moderate Phase 0
depression
Prolong repolarization
Increased duration of action
potential
Includes
– Quinidine – 1st antiarrhythmic
used, treat both atrial and
ventricular arrhythmias,
increases refractory period
– Procainamide- increases
refractory period
– Disopyramide – extended
duration of action, used only for
treating ventricular arrthymias
Group I B
Weak Phase 0 depression
Shortened phase 3 repolarization
Decreased action potential duratio
Includes
– Lidocaine (also acts as local
anesthetic) – blocks Na+ channels
mostly in ventricular cells, also good
for digitalis-associated arrhythmias
– Mexiletine - oral lidocaine derivative,
similar activity
– Phenytoin – anticonvulsant that also
works as antiarrhythmic similar to
lidocane
Classification of antiarrhythmics
(based on mechanisms of action)

Subclass IB
Weak Phase 0 depression
Shortened depolarization
Decreased action potential duration ???
Includes
– Lidocaine (also acts as local anesthetic) – blocks
Na+ channels mostly in ventricular cells, also
good for digitalis-associated arrhythmias
– Mexiletine - oral lidocaine derivative, similar
activity
– Phenytoin – anticonvulsant that also works as
antiarrhythmic similar to lidocane
Group I C
Strong Phase 0 depression
No effect of depolarization
No effect on action potential duration
Includes
– Flecainide (initially developed as a
local anesthetic)
»Slows conduction in all parts of
heart,
»Also inhibits abnormal
automaticity
– Propafenone
»Also slows conduction
»Weak β – blocker
»Also some Ca2+ channel blockad
Class II : β–adrenergic blockers
Based on two major actions
1) blockade of myocardial β–adrenergic receptors
2) Direct membrane-stabilizing effects related to Na+
channel blockade

Includes
Propranolol
– causes both myocardial β–adrenergic blockade
and membrane-stabilizing effects
– Slows SA node and ectopic pacemaking
– Can block arrhythmias induced by exercise
– Other β–adrenergic blockers have similar
therapeutic effect
Metoprolol , Nadolol, Atenolol, Acebutolol,
Pindolol, Satalol, Timolol, Esmolol
Group III- K+ channel blockers
Developed because some patients
negatively sensitive to Na channel
blockers (they died!)
Cause delay in repolarization and
prolonged refractory period
Includes
Amiodarone – prolongs action
potential by delaying K+ efflux but
many other effects characteristic
of other classes
Ibutilide – slows inward movement
of Na+ in addition to delaying K +
influx.
Bretylium –suppress ventricular
fibrillation associated with
myocardial infarction
Dofetilide - prolongs action
potential by delaying K+ efflux with
no other effects
Group IV
Ca2+ channel blockers

slow rate of AV-conduction

in patients with atrial
fibrillation

Includes
Verapamil – blocks Na+
channels in addition to Ca2+;
also slows SA node in
tachycardia
Diltiazem
CLASSIC 4 TYPE OF A A