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Dr Nauman

Learning Objectives

Classify Anti-Arrhythmic Drugs

Describe mechanism of action,
uses and adverse effects of
Quinidine, Procainamide,
Lignocaine Amiodarone and
Describe role of Beta Blockers and
Calcium Channel Blockers in
treatment of arrhythmias

Basic Mechanisms of AntiArrhythmic Drugs

1. Decreasing Automaticity
a) Decreasing Slope of Phase 4 of
AP (Gradual Depolarization)

All Anti-arrhythmic
Decrease Enhanced
By blocking Na,
or Ca Channels

b) Shifting Threshold Potential

Towards Zero (Making
Threshold Potential Less
Decreases Automaticity and
Class 1A, Class II, Class IV

c) Shifting Resting Potential

away from Zero (Making it
more negative)
Slows the rate of Diastolic

2. Decreasing Re-entry
a) Increase Refractory Period
By increasing action potential
Increase in RP in tissues near the
block, the greater the chance the
tissue will still be refractory when
reentry is attempted

Class IA, Class III


Damage e.g.
thrombotic clot,
causes muscle to
become ischaemic


b) Decrease Refractory Period

By decreasing the action
The shorter the RP in depressed
region, the less likely it is that
unidirectional block will occur
Class IB Drugs

c) Slow Conduction
(By decreasing Na or Ca
Conduction fails due to weak
impulse or impulse arrives so
late that it collides with the
next regular impulse

d) Increase Conduction
Impulse will travel around the
obstacle too rapidly and hence
reach tissue that is still

State Dependent Block

Most Anti-arrhythmic agents

block myocardial Na, Ca or K
Channels in a state dependent
That means they bind with a
higher affinity to activated or
inactivated channels than to
resting channels

The central concept is of usedependent block. This feature

enables Drugs to block the
high frequency excitation of
the myocardium that occurs in
tachycardias, without
preventing the heart from
beating at normal frequencies

Thus with each action potential,

drugs bind to Na channels and
block them and with each
diastolic interval drugs
dissociate and unblock
When Heart rate increases,
time available for unblocking
decreases, and steady state Na
Channel Block increases

The rate of recovery from

block also slows as cells are
depolarized, as in ischemia
(Hence more block in ischemic
Increase in action potential
duration causes increase time
spent in inactivated state

Class 1 Drugs-The Na
Channel Blockers

Effects of Blockage of Na
1. Slowing of the Rate and
amplitude of Phase 0
2. Reduces cell excitability
3. Reduces conduction velocity
4. They decrease the slope of
Phase 4 depolarization in cells
with abnormal automaticity

5. The RMP becomes more

negative which decreases
automaticity and excitability
6. Some may also increase
threshold potential

Class I drugs are subdivided

into 3 groups according to
their rate of dissociation from
the channels and according to
the AP and RP duration

Class IA

These drugs bind more to open

channels than inactivated
channels and they dissociate
slowly from the channels
These drugs block Na as well
as K+ channels and thus
prolong action potential
duration and refractory period

In therapeutic concentrations,
1. Raise threshold for excitation
(lengthen AP duration)
2. Cause minor slowing of
Intracardiac conduction
3. Widen QRS Complex
4. Prolong RP in atria and ventricles

This is the Prototype 1A Drug
Dextro-isomer of Quinine
Mechanism of Action
a) Blocks Na Channels in open
state and thus reduces
automaticity and maximal rate
of Phase 0 Depolarization

b) Prolongation of AP duration is
due to K Channel Block and the
increase in RP due to its
moderate effect on recovery of
Na Channels
c) Mild alpha and Vagolytic

Mode of Action in
1. Decrease Automaticity by
a) Decreasing slope of Phase 4
b) Shifting threshold potential
towards zero and thus decrease
c) Shifting resting potential away
from zero (making it more

2. Decrease Re-entry by:

a) Increasing Refractory Period
By Potassium Channel
Blockage and by slow recovery
of Na channels
b) Slowing conduction

Effects on ECG
Prolonged PR Interval
Widening of QRS Complex
Blood Pressure
Decrease in Blood Pressure due
to alpha blockage and direct
relaxant effect on blood vessels

Therapeutic Uses
1. Atrial Fibrillation and Atrial
Flutter given after digitalization
2. Paroxysmal Atrial and Nodal
Tachycardia and Ventricular
3. Atrial, nodal and Ventricular
Premature Beats
4. Prevention of Ventricular
Fibrillation and Ventricular Flutter

Adverse Effects
1. Myocardial Depression
2. AV Block
3. Higher Doses: Ventricular
Arrythmias prolonged QRS Complex
and QT interval precipitating Heart
4. Decreased BP and syncope
5. Paradoxical Tachycardia (Vagolytic

4. Torsades de pointes (Twisting of

Points), Serious multiform
ventricular tachycardia with rapid
asynchronous complexes associated
with prolonged QT Interval
Can progress to ventricular fibrillation
or reverse spontaneously
Precipitated by Class 1A, 1C and some
Class III drugs

Extra-Cardiac Adverse
1. GIT Intolerance: Nausea, Vomiting
and Diarrhea
2. Cinchonism: Higher doses: Ringing
in ears, deafness, vertigo,
headache, visual disturbances,
mental changes, delirium
3. Hypersensitivity Reactions
Fever, Thrombocytopenia, hepatitis,
bone marrow depression

Drug Interactions
1. Displaces digoxin from tissue
binding sites and decreases its
renal and biliary clearance
---Increased digoxin levels

Procainamide &
SLE like syndrome

Most Anti-muscarinic effects

Class IB Drugs

These drugs rapidly associate and

dissociate from sodium channels
They block inactivated channels
Actions are thus manifested when
the cardiac cell is depolarized or
firing rapidly
Thus Particularly useful in
treating ventricular arrhythmias

Prototype 1B Drug
Local anesthetic (amide);
extensive first pass; given
Does not effect
electrophysiological function
of atria, SA node and AV Nodes
Thus NOT Effective in
Supraventricular arrhythmias

Produces minimum change in


Toxicity minimal and of short

Little depression of cardiac
contractility or arterial BP
No autonomic actions

Anti-arrythmic Actions of
Class IB
1. Decreased Automaticity
Decreases slope of Phase 4
Depolarization in Purkinje fibers
2. Decreased Re-entry
Decreases refractory period of
Purkinje fibers and ventricles
---abolishes one way block

1. Used to control ventricular
arrythmias especially in emergency
e.g. after MI
2. Suitable for treatment of digitalis
induced ventricular arrythmias
because it lacks action on
atrioventricular nodal conduction
3. Prophylactically used to prevent
ventricular arrythmias during

4. Used as a local anaesthetic

alone or with adrenaline
Adverse Effects
Safest Anti-arrythmic
Only excessive doses cause
cardiac depression and

Neurological-like all other local
tremor, lightheadedness,
hearing disturbances, slurred
speech and convulsions
Drowsiness, disorientation,
muscle twitchings

Class IC Drugs
These drugs markedly slow Phase 0
They have a very slow rate of
association and dissociation with
sodium Channels
Used for refractory ventricular
Minor effect on AP and RP durations
Very arrhythmogenic-rarely used

Class III Drugs

These agents block Potassium

Thus they diminish outward
potassium current during
They prolong the duration of AP
without altering phase 0
Prolong Effective Refractory Period

Broad Spectrum Anti-arrythmic Drug
Contains Iodine: Structure similar to
Blocking Actions
Potassium Channel Blocker
Sodium Channel Blocker
Weak Ca Channel Blocker
Weak Beta Blocker

Anti-arrythmic Effects
1. Decreased Automaticity
Preferentially block
inactivated Na Channels with
rapid rate of Channel Recovery
2. Decreased Reentry
a) Increase Refractory Period
Prolonged AP duration and
ERP due to K Channel Block

b) Slowed Conduction
Calcium channel blockage and
Beta Blockade cause slowed
conduction and prevents reentry
Therapeutic Uses
a) Chronic Ventricular Arrhythmias
b) Atrial Fibrillation and atrial

Adverse Effects of
Heart Block, bradycardia, and
induction of ventricular
arrythmias, Torsades de pointsProlonged QT interval
1. Pulmonary Toxicity-Pulmonary

2. Hepatitis-abnormal LFTs
3. Hypothyroidism-Contains IodineMay cause Hypo or
4. Skin Deposits-Photodermatitis,
Grey-blue Skin Discoloration
5. Corneal MicrodepositsVisual
Disturbances and Photophobia,
optic neuritis and blindness

Role of Beta Blockers in

Treatment of Arrythmias
1. Beta Blockers block beta 1 receptors
of the heartDecrease levels of
cAMPdecrease Calcium and
Sodium influx
2. Sympathetic stimulation increases
the activity of the SA Node
Activity of many excitable foci is
due to presence of catecholamines
Beta blockers are very effective in
treating these arrhythmias

3. Beta Blockers prolong the

refractory period of AV Node (Slow
down AV conduction) -Negative
Dromotropic effect)
-Decrease number of impulses
passing on to ventricles
-Decrease re-entry

4. They depress Phase 4

Depolarization leading to
decreased automaticity
5. HR and contractility are
decreased leading to
decreased EADs and DADs
6. Some Beta Blockers have MSA

7. Sotalol is also a K channel

blocker and thus also classified
under Class III drug
It is useful in supraventricular
arrythmias but causes
Ventricular Tachycardias and
Torsades de pointes

Calcium Channel Blockers

They block L-Type Calcium
channels and thus decrease
calcium current
Mainly Verapamil and Diltiazem
are used because they have
more effects on heart

Mode of Action:
a) Slow AV Conduction and thus
decrease transmission of the
number of impulses passing
onto ventricles, thus useful in
supraventricular arrythmias
b) Prevent Reentry again by
slowing AV Conduction

Miscellaneous Group of
Mechanism of Action
Binds to G-Protein linked
adenosine receptors
a) Activates K Inward current in
the atria, SA and AV Nodes--Shortening of AP Duration,
hyperpolarization and slowing
of normal automaticity

b) Inhibits the effects of

Increased cAMP that occur
with sympathetic stimulation
thus it reduces calcium
currents and increases AV
Nodal Refractoriness
Drug of Choice for PSVT

Adverse Effects of
Chest fullness and dyspnea, flushing
and hypotension, AV Block, atrial
Drug Interactions
Methylxanthines: e.g. Caffeine blocks
adenosine receptors ---more dose
of adenosine required
Dipyridamole: Potentiates action of