1. ANTIARRHYTHMIC DRUGS Department of Pharmacology and Toxicology
Medical University of Sofia, Faculty of Medicine
Department of Pharmacology and Toxicology
ANTIARRHYTHMIC
DRUGS
(Summary)
Assoc. Prof. Ivan Lambev

3. 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).

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

5. 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.

6. 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.

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

8. The cardiac action potential

13. 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.

14. 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.

15. 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.

16. 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

17. 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).

18. 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

19. 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

20. Cinchona succirubra
Quinidine
Chinine
Rauwolfia serpentina
Ajmaline
Reserpine

21. Treatment: Lidocaine, Ajmaline

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

23. Ventricular flutter

24. Class II (-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)
Pindolol, Propranolol
Atenolol, Esmolol

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

26. 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

27. 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.
ADRs: headache, edema,
bradycardia, AV block
Ind: SV arrhythmias.

28. Atrial fibrillation

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

31. 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.

32. Pacemaker

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

35. 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 the
development of a polymorphic ventricular
tachycardia known as “torsades de pointes”.

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

37. Torsades de Pointes: Treatment
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 defibrillation.
See: