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Dr Nauman
Learning Objectives
All Anti-arrhythmic
Decrease Enhanced
Automaticity
By blocking Na,
or Ca Channels
2. Decreasing Re-entry
a) Increase Refractory Period
By increasing action potential
duration
Increase in RP in tissues near the
block, the greater the chance the
tissue will still be refractory when
reentry is attempted
Re-entry
Purkinje
fibre
Damage e.g.
thrombotic clot,
causes muscle to
become ischaemic
Ventricular
muscle
c) Slow Conduction
(By decreasing Na or Ca
Current)
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
refractory
Class 1 Drugs-The Na
Channel Blockers
Effects of Blockage of Na
Channels
1. Slowing of the Rate and
amplitude of Phase 0
Depolarization
2. Reduces cell excitability
3. Reduces conduction velocity
4. They decrease the slope of
Phase 4 depolarization in cells
with abnormal automaticity
Class IA
In therapeutic concentrations,
they
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
Quinidine
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
Actions
Mode of Action in
Arrythmias
1. Decrease Automaticity by
a) Decreasing slope of Phase 4
Depolarization
b) Shifting threshold potential
towards zero and thus decrease
excitability
c) Shifting resting potential away
from zero (making it more
negative)
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
Tachycardia
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
failure
4. Decreased BP and syncope
5. Paradoxical Tachycardia (Vagolytic
effect)
Extra-Cardiac Adverse
Effects
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 &
Disopyramide
Procainamide:
SLE like syndrome
Disopyramide
Most Anti-muscarinic effects
Class IB Drugs
LIGNOCAINE
Prototype 1B Drug
Local anesthetic (amide);
extensive first pass; given
IM/IV
Does not effect
electrophysiological function
of atria, SA node and AV Nodes
Thus NOT Effective in
Supraventricular arrhythmias
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
Indications
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
electroversion
Extracardiac
Neurological-like all other local
anaesthetics-parasthesias,
tremor, lightheadedness,
hearing disturbances, slurred
speech and convulsions
Drowsiness, disorientation,
muscle twitchings
Class IC Drugs
These drugs markedly slow Phase 0
depolarization
They have a very slow rate of
association and dissociation with
sodium Channels
Used for refractory ventricular
arrhythmias
Minor effect on AP and RP durations
Very arrhythmogenic-rarely used
Amiodarone
Broad Spectrum Anti-arrythmic Drug
Contains Iodine: Structure similar to
Thyroxine
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
flutter
Adverse Effects of
Amiodarone
Cardiac
Heart Block, bradycardia, and
induction of ventricular
arrythmias, Torsades de pointsProlonged QT interval
Extracardiac
1. Pulmonary Toxicity-Pulmonary
Fibrosis
2. Hepatitis-abnormal LFTs
3. Hypothyroidism-Contains IodineMay cause Hypo or
Hyperthyroidism
4. Skin Deposits-Photodermatitis,
Grey-blue Skin Discoloration
5. Corneal MicrodepositsVisual
Disturbances and Photophobia,
optic neuritis and blindness
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
Drugs
Adenosine
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
Adverse Effects of
Adenosine
Chest fullness and dyspnea, flushing
and hypotension, AV Block, atrial
fibrillation
Drug Interactions
Methylxanthines: e.g. Caffeine blocks
adenosine receptors ---more dose
of adenosine required
Dipyridamole: Potentiates action of
adenosine