1. © Assoc. Prof. Ivan Lambev E-mail: itlambev@mail.bg
Medical University of Sofia, Faculty of Medicine
Department of Pharmacology and Toxicology
ANTIARRHYTHMIC
DRUGS
(Summary)
© Assoc. Prof. Ivan Lambev

2. BASIC ELECTROPHYSIOLOGY
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).

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

4. 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.

5. 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.

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

7. The cardiac action potential

8. MECHANISMS 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.

9. If the impulse again reaches the “blocked”
tissue distally when it has had sufficient
time 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.

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

11. Subsidiary (or ectopic) pacemakers may develop when a site
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.
Spontaneous depolarization
Threshold potential

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

13. 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 duration of AP.
Ind.: SV and ventricular arrhythmias. IA IB IC
Increase
the duration of AP
Decrease
the duration
No effect on
the duration

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

15. Cinchona succirubra
Quinidine
Chinine
Rauwolfia serpentina
Ajmaline
Reserpine

16. Ventricular fibrillation, characterized
by irregular undulations without
clear ventricular complexes.
Treatment: Lidocaine or
electrostimulation

17. Class II (b-adrenoceptor antagonists)
Reduce the rate
of spontaneous depo-
larization of sinus
and AV nodal tissue
by indirect blockade
of calcium channels.
Ind: SV and ventri-
cular arrhythmias.
( cAMP)
pindolol, propranolol
atenolol, esmolol

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

19. Class III Amiodarone Sotalol, Bretylium 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
t1/ days
ARs: hypo/hyperthyroidism,
pulmonary fibrosis
Sotalol, Bretylium

20. 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.
ARs: headache, edema,
bradycardia, AV block
Ind: SV arrhythmias.

21. Other drugs used in tachyarrhythmias
Adenosine inhibits AV conduction.
The duration of effect is less than 60 s.
used bolus i.v. in SV tachycardia with
narrow QRS complex.
ARs24-h: bradycardia, AV block.
Digoxin reduces conduction
through AV node and is useful to
control atrial flutter and atrial fibrillation.

22. II. AAD used in bradyarrhythmias
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
Atropa belladonna L.

23. III. AAD used in Digitalis arrhythmia
Digitalis purpurea
(foxglove)
Digitalis lanata
Phenytoin
Potassium
chloride
Magnesium
aspartate
Digitoxin
Digoxin

24. PROARRHYTHMIC 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
develop a polymorphic ventricular tachy-
cardia known as “torsades de pointes”.

25. Torsades de Pointes After overdose of AAD from class IA:
Polymorphic ventricular tachycardia
with a twisting axis on the ECG