ANTI ARRYTHMIA

IGMG. Surya Chandra T, Pharmacology Dept., School of Medicine,

Udayana Univ.
 An arrhythmia is any abnormality in
heart rate or rhythm of electrical
conduction through the heart.
Arrhythmias disturb the electrical
activity of the heart and interrupt the
normal sequence of atrial and
ventricular activation and
contraction.
 The physiologic consequences of
arrhythmias are usually a decrease
in cardiac output and blood
pressure. In addition, the electrical
disturbances can lead to life-
threatening arrhythmias such as
ventricular fibrillation and cardiac
arrest.
The type of arrhythmia depends on
the location in the heart and the
severity of the electrical
disturbance.
 TYPES OF ARRHYTHMIAS
The most common types of
arrhythmias include tachycardias,
premature contractions, flutters, and
fibrillations.
 Arrhythmias that originate in
the atria and atrioventricular
(AV) nodal areas are referred
to as supraventricular
arrhythmias (above the
ventrcles)
Paroxysmal atrial tachycardia,
atrial flutter, and atrial
fibrillation
 The ventricles cannot keep up with
the atria and contract at a slower rate.
In atrial fibrillation the atrial rate is
over 350 beats per minute and the
ventricular rhythm is irregular.
This predisposes the atria to the
development of blood clots
(thromboembolism).
 Arrhythmias that originate below the
AV node are referred to as ventricular
arrhythmias.
Ectopic foci, areas of abnormal
impulse generation, may appear
when electrical impulses traveling
through the conduction system are
delayed or blocked.
 Ectopic foci that originate in the
ventricles are referred to as
premature ventricular
contractions (PVCs).
Ventricular tachycardia is a rapid
ventricular rhythm where three or
more PVCs occur consecutively.
Ventricular tachycardia can cause
significant circulatory impairment
and may lead to ventricular
fibrillation.

 The most serious arrhythmia is

ventricular fibrillation, which
constitutes a medical emergency.
During fibrillation, the electrical
activity of the ventricles is
severely disturbed and the
ventricles cannot contract
efficiently enough to maintain
adequate circulation. If not
treated immediately, cardiac
arrest and death will result.
 Electrophysiology of the
Heart
most important aspects of the heart
is the function of several ions that
regulate the electrophysiological
properties of the heart.
The ions are sodium (Na + ),
potassium (K + ), and calcium (Ca 2+
)
 During Phase 0 influx of Na+ ions
depolarizes the cardiac membrane
and generates an action potential.
During Phases 13 the membrane is
undergoing repolarization as K+ ions
efflux out of the cardiac membrane.
 During Phase 2 (plateau) calcium
channels open and Ca++ ions pass
into the muscle cell and function in
myocardial contraction.
In Phase 4 the membrane potential
has returned to its resting level and
is ready for the next action potential
 Ventricular muscle does not
normally display automaticity.
However, it can develop
automaticity when there is
ischemia, excessive
sympathetic stimulation, or
other abnormal conditions.
When this occurs ventricular
muscle can depolarize and
generate a premature
ventricular contraction (PVC).
 Antiarrhythmic drugs that
slow Phase 0, prolong Phases
13, or decrease Phase 4
automaticity produce effective
antiarrhythmic actions.
Most antiarrhythmic drugs
affect the movement of one or
more specific ions and exert
their major antiarrhythmic
action on a specific phase of
the action potential.
 One cautionary note should be
mentioned: all antiarrhythmic drugs
have the potential to make any
existing arrhythmia worse. In
addition, antiarrhythmic drugs can
cause new arrhythmias.
 Antiarrhythmic drugs are usually
classified according to the Vaughn-
Williams classification system, which
organizes the antiarrhythmic drugs
into four major classes based on their
major mechanism of action
 CLASS 1 ANTIARRHYTHMIC
DRUGS: SODIUM CHANNEL
BLOCKERS
The pri-mary effect of Class 1
antiarrhythmic drugs is to slow
depolarization and conduction during
Phase 0 of the action potential.
Class IA antiarrhythmics also slow
the efflux of K ions during
repolarization, which prolongs the
refractory period
 The Class I drugs are
subdivided into three groups
(IA, IB, IC) based on the degree
to which they block Na ions
during depolarization (Phase
0).
IAs produce a moderate block;
IBs, a mild block;
ICs, a marked block of Na influx
(Phase 0).
Each Class I drug also produces a
different effect on the refractory
period
 Quinidine (IA)
In the past quinidine has been used
to treat supraventricular
arrhythmias, and also ventricular
arrhythmias.
However, quinidine is a cardiac
depressant that decreases
myocardial contraction. In addition,
quinidine produces anticholinergic
and alpha-blocking effects.
Consequently, quinidine can cause a
wide range of adverse effects and
potential toxicities and is rarely used
 Procainamide (Procanbid) (IA)
procainamide produces similar
antiarrhythmic actions as quinidine.
However, produces less anticho-linergic
and alpha-blocking actions than
quinidine.
Procainamide causes fewer adverse
effects and toxicities and is the most fre-
quently used IA antiarrhythmic drug
 Lidocaine ( Xylocaine ) (IB)
widely used for ventricular
arrhythmias, especially those
resulting from a myocardial
infarction or arrhythmias
occurring during surgery.
it does not depress normal
impulse conduction. The main
effect of lido-caine, prevention
of ventricular arrhythmias, is
attributed to its ability to
depress automaticity
 Mexiletine ( Mexitil ) (IB)
Mexiletine is a derivative of lidocaine
that has been structurally modified so
that it can be administered orally.
is used for treatment of outpatient
ventricular arrhythmias.
 Class 1C Antiarrhythmic Drugs
Flecainide ( Tambocor ) and
propafenone ( Rythmol )
depress cardiac conduction (Phase
0).
Drug trials with the ICs have
shown that these drugs can
increase the risk of mortality in
patients with preex-isting
arrhythmias and other cardiac
conditions. Also depress
myocardial contractility and may
cause heart failure.
indicated for treatment of
supraventricular arrhythmias
 CLASS 2 ANTIARRHYTHMIC
DRUGS: BETA-BLOCKERS
Frequently, in heart disease, there is
increased sympathetic activity with increased
release of norepinephrine and epinephrine.
These NT increase heart rate, excitability,
conduction, and automaticity, particularly of
ventricular muscle.
shorten the refractory period, all of which can
contribute to the development of various
arrhythmias
 Propranolol
In addition to its beta-blocking effect,
propranolol pro-duces a depressant
effect on cardiac membranes that slows
conduction and prolongs repolarization.
Esmolol
a selective beta-blocker that mainly
affects beta-1 receptors in the heart
 CLASS 3 ANTIARRHYTHMIC
DRUGS: POTASSIUM CHANNEL
BLOCKERS
The main antiarrhythmic action of the
Class 3 drugs is to block potassium
channels and interfere with the efflux
of potassium ions (K+ ) during
repolarization Phases 1 through 3.
This action prolongs the refractory
period of the heart and decreases the
frequency of arrhythmias
 Amiodarone
has multiple sites of action. In addition
to blocking potassium channels,
amiodarone blocks
sodium (Class 1) and calcium (Class 4)
channels.
It also has blocking actions on both beta-
(Class 2) and alpha-adrenergic receptors.
 Sotalol
a nonselective beta-blocker that also
has Class 3 antiarrhythmic activity.
The main effects are prolonga-tion of the
refractory period, slowed AV conduction,
and decreased automaticity of the heart.
 Dofetilide and Ibutilide
Whose actions are limited to blocking
potassium channels.
Dofetilide is administered orally;
ibutilide is adminis-tered intravenously.
 CLASS 4 ANTIARRHYTHMIC
DRUGS: CALCIUM CHANNEL
BLOCKERS
The Class 4 antiarrhythmic drugs are
referred to as the calcium channel
blockers.
These drugs decrease the entry of
calcium into cells whose
electrophysiologic actions depend on
the influx of calcium through the
slow-type calcium channels.
 In the heart, the depolarization
of SA and AV nodal cells is
highly dependent on the influx
of calcium ions.
The effect of calcium channel
blockers on the SA node is to
slow depolarization and
decrease the heart rate. The
effect on the AV node is to slow
conduction.
These actions reduce the
ventricular rate during fast
supraventricular arrhythmias.
 The calcium channel blockers
also affect the contraction of
cardiac and smooth muscle.
entry of calcium during Phase
2 of the action potential is
important for regulating the
force of myocardial
contractions.
Interference with calcium entry
into cardiac muscle reduces
myocardial contractility.
This may precipitate heart
failure in patients with CHF.
 The calcium channel blockers also
relax smooth muscle and cause
vasodilation
While all calcium channel blockers
produce vasodilation, only Verapamil
and have direct actions on the heart
and are used for their antiarrhyth-mic
actions.
 Verapamil
Verapamil decreases SA node
activity, resulting in a slight
decrease in heart rate. More
important, verapamil decreases
AV node conduction

Diltiazem
The cardiac depres-sant effects of
diltiazem are slightly less than
those of verapamil, but diltiazem
is generally considered to be a
more potent vasodilator than
verapamil.