Anti-Arrhythmic drugs

1. ANTIARRHYTHMICANTIARRHYTHMIC
DRUGSDRUGS
(Summary)(Summary)

3. Myocardial cells maintain transmembrane
ion gradients by movement of the Na+
, Ca2+
and K+
through membrane channels.
The resting potential of a cardiac cell is
– 85 mV compared to the extracellular
environment.
Depolarization is initiated by a rapid influx
of Na+
(phase 0).
BASIC ELECTROPHYSIOLOGYBASIC ELECTROPHYSIOLOGY

4. Depolarization
Rapid repolarization
Final repolarization
Plateau
Resting potential Spontaneous
depolarization

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6. In the AV node depolarization is
due to the slower influx of calcium ions.
This results in slower conduction of the
impulse through the AV node than in
other parts of the heart.

7. During the period between phase 0 and the
end of phase 2, the cell is refractory to the
further depolarization (absolute refractory
period) since the sodium channels are
inactivated.
During phase 3, a sufficiently large stimulus
can open enough sodium channels to over-
come the potassium efflux. This is the
relative refractory period.

8. Rapid repolarization
Plateau
Depolarization
Final repolarization
Spontaneous depolarization
Absolute
refractory period Relative refractory period
Threshold potential
Resting membrane
potential

9. The cardiac action potential

14. MECHANISMS OF ARRHYTHMOGENESISMECHANISMS OF ARRHYTHMOGENESIS
Arrhythmias can arise as the result of
abnormal impulse generation or abnormal
impulse conduction. The main mechanisms:
•RE-ENTRY (the most frequently): if an
impulse arrives at an area of tissue when
it is refractory to the stimulus, this impulse
will be conducted by an alternative route.

15. f the impulse again reaches the “blocked”
issue distally when it has had sufficient
ime to recover, the same impulse will be
conducted retrogradely (re-entry).
This retrograde
conduction
is slow, because
to initiate a circuit
of electrical acti-
vity, the healthy
tissue has to be
given time
to repolarize.

16. Such a mechanism can initiate a
selfperpetuating “loop” of electrical
activity which acts as a pacemaker.
The re-entry circuit can be localized
within small a area of the myocardium
or it can exist as a large circuit, for
example between the atria and
ventricles.

17. •AUTOMATICITY
Subsidiary (or ectopic)
pacemakers may
develop when a site
in the myocardium
develops a more
rapid phase
4 depolarization
than the SA node,
e.g. as a result
of ischaemia.
Spontaneousdepolarization
Threshold potential

18. ANTIARRHYTHMIC DRUGS (AAD)ANTIARRHYTHMIC DRUGS (AAD)
I. AAD used in tachyarrhythmias
The Vaughan William’s
Classification of AAD
is based on their
effects on the cardiac
action potential (AP).

19. Class I (membrane stabilizers)
•These AAD slow the rate of raise of phase 0
of AP by inhibiting fast sodium channels.
The class is subdivided according to the
effects of drugs on the duration of AP.
•Indications: SV and ventricular arrhythmias.
IA IB IC
Increase
the duration of AP
Decrease
the duration
No effect on
the duration

20. IA IB IC
Disopyramide
Procainamide
Ajmaline
- weak negative inotropic effect
Quinidine
Lidocaine
Mexiletine
Phenytoin
Propafenone
Flecainide
ADRs: Bradycardia, AV block, (–) inotropic
effect, disturbances of GIT, rashes

21. Rauwolfia serpentina
•Ajmaline
•Reserpine
Cinchona succirubra
•Quinidine
•Chinine

22. Treatment: Lidocaine, Ajmaline

23. Ventricular fibrillationVentricular fibrillation, characterized
by irregular undulations without
clear ventricular complexes.
Treatment: Lidocaine or
electrical defibrillation

24. Ventricular flutterVentricular flutter

25. Class II (β-adrenoceptor antagonists)
•Reduce the rate
of spontaneous depo-
larization of sinus
and AV nodal tissue
by indirect blockade
of calcium channels.
•Indications: SV and
ventricular arrhythmias.
( cAMP)( cAMP)
Pindolol, Propranolol
Atenolol, Esmolol

26. Atrial flutter with a 4:1 conduction ratio.
Esmolol
(short action)

27. Class III
•These AAD prolong
the duration of the AP
and increase the abso-
lute refractory period.
This is the result of
reduced influx of K+
into the cell.
•Ind: SV and ventri-
cular arrhythmias.
Amiodarone (p.o.; i.v. inf.)
t1/2 20–100 days ADRs: bradycardia,
hypo/hyper thyreoidism,
corneal micro-deposits under
pupil, neuritis n. opticus,
pulmonary fibrosis.
Dronedarone (contains no iodine
but has hepatotoxic effect)
Sotalol, Bretylium

28. Class IV (calcium channel antagonists)
•Mainly Verapamil
(22% oral availability)
and Diltiazem (i.v.) from
calcium antagonists
have specific action
on the SA and AV
nodes. They decrease
the duration of AP.
•Ind: SV arrhythmias.
ADRs: headache, edema,
bradycardia, AV block

29. Atrial fibrillationAtrial fibrillation

31. AdenosineAdenosine inhibits AV conduction.
The duration of effect is less than 60 s.
•used as an i.v. bolus in SV tachycardia withSV tachycardia with
narrow QRS complexnarrow QRS complex.
•ADRs: bradycardia, AV block.
Other drugs used in tachyarrhythmias
Digoxin reduces conduction
through the AV node and is useful in the
control of atrial flutter and atrial fibrillation.

32. •Atropine is given
by bolus i.v. inj.
in sinus brady-
cardia and AV
block. It blocks
M2-receptors and
increases conduction
through the AV node.
•Isoprenaline
is used in AV block
II. AAD used in bradyarrhythmiasII. AAD used in bradyarrhythmias
AtropabelladonnaL.

33. Pacemaker

34. Digitalis purpurea
(foxglove)
Digitalislanata
Digitoxin Digoxin
•Phenytoin
•Potassium
chloride
•Magnesium
aspartate
•Digoxin-
specific FAB
(Fragment
AntiBody):
Digibind®
(38 mg
connect
0,5 mg
Digoxin)
III. AAD used in Digitalis arrhythmiaIII. AAD used in Digitalis arrhythmia

36. PROARRHYTHMIC ACTIVITY OF AADPROARRHYTHMIC ACTIVITY OF AAD
•All AAD have the potential to precipitate
serious arrhythmias, particularly ventri-
cular tachycardia or fibrillation.
•Mainly the AAD from class IA prolong
the Q–T interval which predisposes to the
development of a polymorphic ventricular
tachycardia known as “torsades de pointes”.

37. Polymorphic ventricular tachycardia
with a twisting axis on the ECG
Torsades de PointesTorsades de Pointes

38. Treat hypokalemia if it is the precipitating factor and administer
magnesium sulfate in a dose of 2–4 g i.v. initially.
Magnesium is usually very effective, even in the patient with a
normal magnesium level. If this fails, repeat the initial dose, but
because of the danger of hypermagnesemia (depression of
neuromuscular function) the patient requires close monitoring.
Other therapies include overdrive pacing and isoprenaline infusion.
Most (75–82%) torsade de pointes rhythms are started by a
pause. Pacing at rates up to 140 bpm may prevent the ventricular
pauses that allow torsade de pointes to originate.
The patient with torsade who is in extremis should be treated
with electrical cardioversion or defibrillationelectrical cardioversion or defibrillation.
See: http://emedicine.medscape.com/article/760667-treatment
Torsades de Pointes: TreatmentTorsades de Pointes: Treatment