Materi Kuliah Farmakologi Blok Kardiovaskular Fakultas Kedokteran - Universitas Muhammadiyah Purwokerto

1. Obat Antiarritmia
M Fadhol Romdhoni
Laboratorium Farmakologi
Fakultas Kedokteran UMP

2. 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

3. Normal heartbeat and atrial arrhythmia
Normal rhythm Atrial arrhythmia
AV septum

4. 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 outside than inside cel
K+ higher inside cell than outside
Maintenance by ion selective channels, active
pumps and exchangers

5. ECG (EKG) showing wave
segments
Contraction
of atria
Contraction of
ventricles
Repolarization of
ventricles

6. 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

7. 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

9. 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

10. Obat antiarritmia

11. 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

13. Group I B
Weak Phase 0 depression
Shortened phase 3 repolarization
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

14. 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

15. 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

16. 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

18. 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

19. CLASSIC 4 TYPE OF A A