This document discusses the classification and properties of antiarrhythmic drugs. It describes the Vaughan Williams classification which categorizes drugs based on their primary site of action as sodium channel blockers (Class I), beta blockers (Class II), potassium channel blockers (Class III), or calcium channel blockers (Class IV). Class I drugs are further divided into IA, IB, and IC based on their effects on action potential duration and kinetics of sodium channel binding. The document also discusses the mechanisms of action and effects of blocking specific ion channels involved in cardiac rhythms.

1. ANTI ARRHYTHMIC DRUGS - I
Dr D SUNIL REDDY

2. NORMAL CARDIAC AP

3. IONIC BASIS OF CARDIAC AP

6. • Automaticity is the property to initiate an impulse
spontaneously, without need for prior stimulation, so
that electrical quiescence does not occur.
• Triggered activity is pacemaker activity that results
consequent to a preceding impulse or series of
impulses, without which electrical quiescence occurs
• These are called early afterdepolarizations (EADs),
when they arise from a reduced level of membrane
potential during phases 2 (type 1) and 3 (type 2) of
the cardiac AP
• Late or delayed afterdepolarizations (DADs), when
they occur after completion of repolarization (phase
4), generally at a more negative membrane potential
than that from which EADs arise.

7. EFFECTS OF BLOCKING Na CHANNEL
• Decrease in conduction velocity (dromotropy) manifest
as widening of QRS duration ( decreased rentry )
• Increase action potential threshold ( decreased
automaticity /pacing threshold)
• Slight decrease in AP duration (QT interval)
• Negative inotropy
( Lower Na+ permeability through the channel
means less Na+ in the cell. More Na/Ca exchange -
less intracellular Ca 2+ and less contractility )

8. • Na+ blockers have a greater propensity to bind to
channels in the active state, the faster the rate, more
the binding and more the anti arrhythmic effect.
• This is called use dependence, a property of Na+
channel blockers

9. EFFECTS OF BLOCKING K CHANNEL
• Main effect = Increased APD = increased
refractoriness (Decreased reentry ); ( longer QT ) „
• Many K+ Ch blockers have a reverse use dependent
effect ( binds to resting channels) : AP prolongation
is greater at slower rather than at faster rates =
EAD
• Increased risk of triggered activity ( EAD ) leads to
proarrhythmias

10. • Na blockade
Na CHANNEL
BLOCKADE
K CHANNEL
BLOCKADE

12. EFFECTS OF BLOCKING Ca CHANNEL
• Inhibit the SA & AVN, and tissue with abnormal
automaticity dependent on Ca2+channels (e.g. RVOT)
• Generally little effect on the APD
• Stops triggered activity ( EAD and DAD )
• EADs due to oscillatory depolarisations due to waves of
Ca2+ channel reactivation
• DADs result from Ca 2+ overload of the cell

13. EARLY AFTER DEPOLARISATIONS

14. DELAYED AFTERDEPOLARISATION

15. ANTI ARRHYHTMIC AGENTS
• Most of the available antiarrhythmic drugs can be
classified according to whether they exert
blocking actions predominantly on
– Sodium channels
– Potassium channels
– Calcium channels
– whether they block receptors (eg. Beta rec.)

16. VAUGHAN WILLIAMS SINGH AND
HAUSWIRTH CLASSIFICATION
• In 1970, Vaughan Williams proposed a classification
based on possible ways in which abnormal cardiac
rhythms could be corrected or prevented
• In 1974, Singh and Hauswirth modified the
classification, with two major changes.
• First, lignocaine and Phenytoin were placed in a
separate class, because at low concentrations and at
low external potassium concentrations, they had
little effect upon the AP or cardiac conduction.
• Secondly, a separate class (now class IV) was
introduced to accommodate CCB

17. VAUGHAN-WILLIAMS CLASSIFICATION
Cla
ss
Action Drugs Primary site of
action
I Na channel blockade
Ia QUINIDINE,PROCAINAMIDE, DISOPYRAMIDE HP , A , V
Ib LIDOCAINE, MEXILETINE,PHENYTOIN V
Ic FLECAINIDE, PROPAFENONE, MORICIZINE HP , V
II ß- blockade PROPRANOLOL, METOPROLOL,
ESMOLOL, ACEBUTOLOL
SAN, AVN
III Potassium
channel
blockade
SOTALOL, DOFETILIDE,
AMIODARONE, BRETYLIUM,
IBUTILIDE
A , V , AVN ,
SAN, HP, Acc P
IV CCB VERAPAMIL, DILTIAZEM AVN

18. DRAWBACKS OF VWSH CLASSIFICATION
• Over simplification of the effect of these drugs
• It relies on the effect these agents have on
normal tissue and under arbitrary conditions
• The major effect an agent from one group has,
overlaps with the effect of agents from other
groups .

19. SICILIAN GAMBIT CLASSIFICATION OF
ARRHYTHMOGENIC MECHANISMS
• Formulated by the European Society of Cardiology
working group
• It seeks the critical mechanisms responsible for
arrhythmogenesis to identify a “vulnerable
parameter” of the arrhythmia concerned
• Drugs are classed based on their differential effects
on
(1) Channels
(2) Receptors and
(3) Transmembrane pumps

21. CLASS I ANTIARRHYTHMICS
• Class I drugs predominantly block the fast Na+
channel (may block K+ channels as well)
• Group 1 drugs are further subdivided on the
basis of their effects on AP duration
– Group 1A agents - prolong the AP
– Group 1B drugs - shorten the AP in some
cardiac tissues.
– Group 1C drugs - have no effect on APD

22. • The class IC agents have the slowest binding and
dissociation from the receptor.
• The class IB agents have the most rapid binding and
dissociation from the receptor.
• The class IA agents are intermediate in terms of the
speed of binding and dissociation from the receptor.
• Use-dependence is seen most frequently with the
class IC agents, less frequently with the class IA
drugs, and rarely with the class IB agents

23. CLASS – I A
• This class includes drugs that depress phase 0
(sodium-dependent) depolarization, thereby slowing
conduction and prolong action potential duration
• QUINIDINE, PROCAINAMIDE AND DISOPYRAMIDE.
• Their kinetics of onset and offset in blocking the Na+
channel are of intermediate rapidity (less than 5
seconds) compared with class IB and class IC agents
• These drugs affect both atrial and ventricular
arrhythmias.
• They block INa, and therefore slow conduction velocity
in the atria, Purkinje fibers, and ventricular cells.

24. • They also have moderate potassium channel blocking
activity (which tends to slow rate of repolarization
and prolong action potential duration [APD]),
• They also have anticholinergic activity, and tend to
depress myocardial contractility.
• At slower heart rates, when use-dependent blockade
of the sodium current is not significant, potassium
channel blockade may become predominant (reverse
use-dependence), leading to prolongation of the APD
and QT interval and increased automaticity.

25. CLASS I B
• This class of drugs does not reduce rate of rise of AP
upstroke and shortens AP duration
• MEXILETINE, PHENYTOIN, AND LIDOCAINE
• Their kinetics of onset and offset in blocking the
sodium channel are rapid (less than 500
milliseconds).

26. • The class IB drugs have less prominent sodium
channel blocking activity at rest, but effectively block
the sodium channel in depolarized tissues.
• They tend to bind in the inactivated state (which is
induced by depolarization) and dissociate from the
sodium channel more rapidly than other class I
drugs.
• As a result, they are more effective with
tachyarrhythmias than with slow arrhythmias.

27. CLASS I C
• This class of drugs can reduce rate of rise of AP
upstroke , primarily slow conduction velocity, and
prolong refractoriness minimally
• FLECAINIDE , PROPAFENONE AND MORICIZINE
• These drugs have slow onset and offset kinetics (10
to 20 seconds).

28. • Class IC drugs primarily block open sodium channels
and slow conduction.
• They dissociate slowly from the sodium channels
during diastole, resulting in increased effect at more
rapid rate (use-dependence).
• This is the basis for their antiarrhythmic efficacy,
especially against supraventricular arrhythmias.
• Use-dependence may also contribute to the
proarrhythmic activity of these drugs, especially in the
diseased myocardium, resulting in incessant
ventricular tachycardia.

30. GROUP II ( BETA BLOCKERS )
• They decrease depresses SA node automaticity and
prolong the refractoriness of the AV node
• Blockers may prevent shortening of refractoriness at
all levels in the heart.
• They also block adrenergic activation of Ca channels.
• In addition, beta2 receptors are implicated in
ischemia-dependent ventricular fibrillation, which
may be prevented by nonselective blockade

31. • These agents also act on:
– I f , important pacemaker current that promotes
proarrhythmic depolarization in damaged heart
tissue
– The inward calcium current, which is indirectly
inhibited as the level of tissue cAMP falls.
• Blockers may suppress non sustained ventricular
arrhythmias, especially in patients with an underlying
adrenergic mechanism.
• Consequently, they are the drugs of choice in
exercise-induced arrhythmias and in patients with
long QT syndrome, especially LQT1

34. CLASS III ANTI ARRHYTHMICS
• The hallmark of group 3 drugs is prolongation of the
AP duration.
• This AP prolongation is caused by blockade of
IK potassium channels (during phase II and III of AP)
that are responsible for the repolarization of the AP
leading to an increase in effective refractory period
• They do not impact conduction

35. • MIXED CLASS III – AMIODARONE , SOTALOL
• PURE CLASS III – IBUTILIDE AND DOFETILIDE

37. CLASS IV (CCB)
• They are effective in arrhythmias that must traverse
Ca-dependent cardiac tissue (eg, AVN)
• These agents cause a use-dependent selective
depression of calcium current in tissues that require
the participation of L-type Ca channels
• AV conduction velocity is decreased and effective
refractory period increased by these drugs.
• PR interval is consistently increased

40. THANK YOU

48. • It is especially important to adhere to the
following fundamental principles of drug therapy:
• Define a benefit for therapy.
• Define an end point for therapy.
• Minimize the risks (and ensure that these do not
outweigh the expected benefits).
• Define the need for therapy.
• Consider alternative therapies.

49.  Class IA
• Slows conduction velocity (less than class IC) and
prolongs action potential duration (APD)
• Disopyramide Procainamide Quinidine
 Class IB –
• They have no effect on conduction velocity and may
shorten APD
• Lidocaine Mexiletine Phenytoin
 Class IC –
• Slows conduction and may prolong APD
• Flecainide Propafenone

50. PROPERTIES
FAST RESPONSE
TIMES
SLOW RESPONSE TIMES
Location Atria, specialized
infranodal conducting
system, ventricles, AV
bypass tracts
Sinoatrial and atrioventricular
nodes, depolarized fast
response tissues in which phase
0 depends upon calcium current
PASSIVE CELLULAR PROPERTIES
Resting
Potential
-80 to -95 mV -40 to -65 mV
ACTIVE CELLULAR PROPERTIES
Phase 0
current
Sodium Primarily calcium
Phase 0
channel
kinetics
Fast Slow activation; inactivation
depends upon voltage and cell
calcium concentration
Peak
overshoot
+20 to +40 mV -5 to + 20 mV
AP amplitude 90 to 135 mV 30 to 70 mV

51. PROPERTIES DEPENDENT UPON ACTIVE AND
PASSIVE PROPERTIES
Threshold voltage -60 to -75 mV -40 to -60 mv
Conduction velocity 0.5 to 5 m/sec 0.01 to 0.1 m/sec
Conducive
To
reentry
Only with
inactivation of
sodium
channels with
marked
slowing of
conduction
velocity
Present in normal
tissue
Automaticity Yes Yes