Antiarrhythmic Drugs

ANTIARRHYTHMIC DRUGS and propagates to the rest of
(AADs) the heart-PACEMAKER

CONTENT v. Other automatic fibers
Physiology of normal cardiac have slower phase-4
rhythm depolarization- receive
Definition and mechanisms impulse from SAN.
of arrhythmias vi. Latent pacemakers
Classification of drugs to BASIC CARDIAC
treat arrhythmias ELECTROPHYSIOLOGY
Important anti-arrhythmic 2. Conduction
drugs (mechanism and A more completely
pharmacological polarized membrane
characteristics) depolarizes faster because
more Na+ channels have
BASIC CARDIAC recovered (voltage
ELECTROPHYSIOLOGY -dependent reactivation):
1. Impulse generation seen in atrial, ventricular
Nonautomatic myocardial and Purkinje fibers
fibers cannot generate an SAN and AVN remain
impulse on their own. refractory for sometime:
Resting membrane potential Ca2+ channel reactivation is
(RMP) is -90mv time-dependent
Automatic fibers in SA and Purkinje fibers have highest
nodes, His-Purkinje system. conduction velocity
Phase-4 or slow diastolic BASIC CARDIAC
depolarization: Sudden ELECTROPHYSIOLOGY
depolarization occurs 3. Excitability: strength of
spontaneously. stimulus required to produce an
BASIC CARDIAC action potential (AP)
ELECTROPHYSIOLOGY Hyperpolarization decreases
iv. SA node (SAN) has the excitability
steepest phase-4 Decrease in RMP increases
depolarization, self-excitatory excitability
BASIC CARDIAC to spread across the
ELECTROPHYSIOLOGY myocardium
4. Refractory period.
Effective refractory period PHASES OF ACTION
(ERP): Minimum interval POTENTIAL OF CARDIAC
between two APs. CELLS
ERP is closely related to Phase 0 rapid depolarisation
APD (inflow of Na+)
ERP/APD is <1 in fast Phase 1 partial repolarisation
channel fibers (Na+ (inward Na+ current
channels) deactivated, outflow of K+)
ERP/APD is > in slow Phase 2 plateau (slow inward
channel fibers (Ca2+ calcium current)
channels Phase 3 repolarisation (calcium
Most antiarrhythmic drugs current inactivates, K+ outflow)
increase ERP/APD ratio Phase 4 pacemaker potential
(Slow Na+ inflow, slowing of K+
outflow) autorhythmicity
Refractory period (phases 1-3)
045 The Pacemaker Potential of
PHYSIOLOGY OF CARDIAC the SA Node and the AV
RATE AND RHYTHM Node.mp4
Cardiac myocytes are
electrically excitable SINUS RHYTHM
Resting intracellular voltage of
myocardial cells is negative Sinoatrial rate controlled by
-90mV (SA node is -40mV) autonomic nervous system
Resting state - K+ inside and Parasympathetic system
Na+ outside cell (Na+/K+ pump) predominates (M2 muscarinic
Action potential occurs when receptors)
Na+ enters the cell and sets up a Sympathetic system (1 receptors)
depolarising current Increased heart rate (positive
Stimulation of a single muscle chronotropic effect)
fibre causes electrical activity Increased automaticity
Facilitation of conduction of
AV node Mechanisms of dysrhythmias
DEFINITION OF Increased/ectopic pacemaker
ARRHYTHMIA activity
Cardiac arrhythmia is an After-depolarizations: Early
abnormality of the heart rhythm after-depolarization (EAD)
Bradycardia heart rate slow Delayed after-depolarization
(<55-60 beats/min) (DAD)
Tachycardia heart rate fast (>100 3. Reentry
beats/min) Circus movement reentry
CLINICAL CLASSIFICATION Functional reentry
OF ARRHYTHMIAS Fractionation of impulse
Heart rate (increased/decreased) MECHANISMS OF

Heart rhythm (regular/irregular) ARRHYTHMIA PRODUCTION
Site of origin (supraventricular / Re-entry (refractory tissue
ventricular) reactivated due to conduction
Complexes on ECG block, causes abnormal continuous
(narrow/broad) circuit; eg accessory pathways
ANTIARRHYTHMIC DRUGS linking atria and ventricles in
Antiarrhythmic drugs are Wolff-Parkinson-White syndrome)
used to prevent or treat Abnormal pacemaker activity in
abnormal cardiac rhythms. non-conducting/conducting tissue
Abnormal automaticity, (eg ischemia)
impaired conduction or both Delayed after-depolarisation
cause cardiac dysrhythmias. (automatic depolarisation of
Cardiac dysrhythmias cardiac cell triggers ectopic beats,
Causes: can be caused by drugs; eg
Ischemia digoxin)
Electrolyte & pH imbalance
Mechanical injury Important cardiac dysrhythmias
Stretching (CHF) Extrasystoles [ES]:
Neurogenic premature ectopic beats from
Drugs, including AADs an ectopic focus in atrium,
AV node or ventricle
PSVT: atrial tachycardia Third degree: Complete
(150-200/min) heart block. Ventricle
Atrial flutter: 200-350/min. generates own impulses
AV node cannot transmit Cardiac Dysrhythmia
impulses faster than 200/min Heartbeat Dances.mp4
Atrial fibrillation: 350-550/ Classification of AADs: Based on
min, asynchronous their effects on AP (Singh &
Ventricular tachycardia: 4 Williams)
or more consecutive Class I (membrane
ventricular extrasystoles stabilizers):Na+ channel blockers
Important cardiac dysrhythmias These AADs slow the rate of
6. Torsades de pointes: raise of phase 0
Polymorphic ventricular of AP by inhibiting fast sodium
tachycardia, asynchronous channels.
complexes The class is subdivided
7. Ventricular fibrillation: according to the
Uncoordinated contraction of effects of drugs on the duration of
ventricular fibers with loss of AP.
pumping function. Indications: SV and
Death within 2-5 mins. Most ventricular arrhythmias.
common cause of sudden
cardiac death Class I (membrane stabilizers)
Important cardiac dysrhythmias
8. A-V block: Depressed impulse Quinidine Lignocaine
conduction through AVN and Flecainide
bundle of His. Procainamide Phenytoin
First degree: Prolonged P- Propafenone
R interval Disopyramide Mexilitine
Second degree: Some Tocainide
supraventricular complexes
are not conducted: drop Class II (-adrenoceptor
beats antagonists)
Reduce the rate
of spontaneous depo-
larization of sinus Class II: -adrenoceptor
and AV nodal tissue antagonists (atenolol, sotalol)
Indications: SV and Class III: prolong action
ventricular arrhythmias. potential and prolong refractory
period (suppress re-entrant
Propranolol, sotalol, rhythms) (amiodarone,
esmolol dronedarone, sotalol)
Class IV: Calcium channel
Class III antagonists. Impair impulse
propagation in nodal and
These AADs prolong
damaged areas (verapamil)
the duration of the AP
Mechanism of Action of
and increase the abso-
Antiarrhythmic Drugs.mp4
lute refractory period.
This is the result of
block of K+ channels
Other drugs used in
Ind: SV and ventri- tachyarrhythmias
Amiodarnone, dronedarnone,
cular arrhythmias. Adenosine inhibits AV conduction.
dofetilide, ibutilide The duration of effect is less than
60 s.Used as an i.v. bolus in SV
Class IV (CCBs) tachycardia with narrow QRS
complex.
SINGH &WILLIAMS ADRs: bradycardia, AV
CLASSIFICATION OF block.
ANTIARRHYTHMIC DRUGS Digoxin reduces conduction
Class I: block sodium channels through the AV node and is useful
Ia (quinidine, in the control of atrial flutter, atrial
procainamide, fibrillation and PSVT
disopyramide) AP AADs used in bradyarrhythmias
Ib (lidocaine, mexiletine, Atropine is given by bolus
phenytoin) AP i.v. inj. in sinus brady-
Ic (flecainide, propafenone) cardia and AV block. It blocks
AP M2-receptors and
increases conduction through the No effect on AP of atrial
AV node. fibers (short duration of
Isoprenaline is used in AV block inactive Na+ channels).
Class IA:Procainamide No effective in treating
Orally active amide form of atrial and SVTs
procaine PKE: Orally ineffective,
MOA: given IV, action lasts for 10-
Blocks open Na+ channels 20 mins
Reduces automaticity Class IB:Lignocaine
Slows phase 0 depolarization ADRs
Prolongs APD, ERP, QRS CNS: Drowsiness,
complex and Q-T interval parasthesias, disorientation,
PKE: Oral, IV. Acetylation in nystagmus, twitchings and
liver. convulsions
Rapid and slow acetylators CVS: Hypotension and
Class IA:Procainamide cardiac depression
ADRs: Uses:
Cardiac: Hypotension, VT
torsades de pointes Prevent VF
Rash, fever, angioedema Selected cases of MI to
SLE with long term use, prevent VF
especially in slow Digitalis-induced VTs
acetylators Difference between
Uses: Occasionally to lignocaine for VT and LA
terminate VT and SVT.
Class IB:Lignocaine Class IC: Propafenone
MOA: MOA:
Blocks inactive Na+ channels Blocks Na+ channels
( use-dependent)Voltage Depresses impulse
Gated Channels.flv transmission in HP and
Suppresses automaticity of accessory pathways (WPW)
ectopic foci Prolongs APD
Decreases APD in PF and blocking property
ventricular muscle PKE: Oral
ADRs: Blurred vision, bitter IV to terminate torsades de
taste, nausea, vomiting, pointes
constipation, CHF & Sotalol
bronchospasm MOA:Non-selective -
Propafenone blocker, with Class III
Uses actions: Blocks inward
Prophylaxis and treatment of rectifier K+ channels
VTs Delays A-V conduction,
Reentrant tachycardias prolongs ERP
To maintain sinus rhythm in ADRs
AF Uses:
Class II Propranolol Polymorphic VTs
MOA: Non-selective - WPW arrhythmias
blocker with membrane To maintain sinus rhythm in
stabilizing activity. No ISA AF/AFl
Decreases slope of phase-4
depolarization and
automaticity in SAN, PF and Esmolol
ectopic foci, when due to MOA: Ultrashort acting
increased sympathetic cardioselective -blocker
activity without ISA/MSA
Prolongs ERP of AVN Given IV, t1/2 < 10 mins
Reentrant impulses through Uses:
AVN are abolished To terminate SVTs
ECG: prolongs PR interval Episodic AF/Afl
Propranolol Arrhythmia during anesthesia
ADRs: Early treatment of MI
Uses: During and after cardiac
Sinus tachycardia surgery- to reduce HR and
Atrial and nodal ESs BP
Prevent PSVT Class III
Pheochromocytoma Prolong phase-3
Halothane induced Widen AP
dysrhythmias Increases ERP
Terminates reentrant Hypotension, bradycardia,
arrhythmias myocardial depression
Class III: Amiodarone (Iodine Photosensitization
containing) Corneal microdeposits-
MOA: reversible o discontinuation
Blocks delayed rectifier K+ Pulmonary fibrosis &
channels : APD and Q-T alveolitis
prolonged Peripheral neuropathy
Blocks inactive Na+ Inhibits peripheral T4 to T3
channels: conversion
Partial L-type CCB activity Hypo/ hyperthyroidism
Partial -blocker activity
I.V injection causes Dronedarone
myocardial depression and Noniodinated congener of
hypotension amiodarone
Amiodarone MOA: Similar to amiodarone
PKE: Action is delayed on Uses: To maintain sinus
oral administration: rhythm in
Accumulation in muscle and SVTs, PSVT
fat AF/ Afl
t1/2: 3-8 weeks ADRs: Bradycardia,
Uses: weakness, cough, skin
VTs, SVTs, PSVT reactions,
AF, AFl No risk of Pulmonary fibrosis
Resistant & recurrent VF & alveolitis
WPW tachyarrhythmia Neuropathy, hypo/
Broad spectrum , long hyperthyroidism
duration & less
prodysrhythmogenic
potential
Dofetilide
Pure Class III
Amiodarone
ADRs:
MOA: Blocks delayed MOA
rectifier K+ channels : APD Effects
and ERP prolonged Uses:
No action on other receptors To control ventricular rate in
Uses: TO maintain sinus AF/AFl: Given I.V
rhythm in converted patients Preferred to verapamil: Less
of AF & AFl hypotension, cardiac
ADRs: Headache, dizziness, depression, better dose
nausea, rarely allergic skin titration, can be used in
reactions presence of mild-to-
Class IV: CCBs moderate CHF
Verapamil ADRs:
MOA: Blocks L-type Ca2+ Drugs used in tachyarrhythmias
channels Adenosine
Negative inotropic MOA:
SAN automaticity is reduced: Via A1 receptors it activates
Bradycardia ACh sensitive K+ channels on
AV nodal ERP is prolonged: SAN, AVN and atrium
reentry terminated Depresses SAN activity,
Given I.V., oral slows AV conduction and
ADRs: Bradycardia, nausea, atrial excitability
constipation, heart block. Also reduces Ca2+ current in
D/I: -blockers, digoxin AVN
Reduced AVN conduction is
Class IV: CCBs responsible for terminating
Verapamil PSVTs
Uses: Adenosine
AF/AFl
PSVT Given rapid I.V
Taken up by RBCs and
endothelial cells
t1/2: 10 secs
Class IV: CCBs Advantages in PSVT
Diltiazem 1. Efficacy verapamil
2. Duration of action < 1 min-
ADRs transient Drugs for AV block
3. Can be given in CHF, Implanted cardiac pacemaker
hypotension and with -blockers Atropine:
4. Safe in wide QRS tachycardia When block is due to vagal
(verapamil is C/I) overactivity/ some cases of
5. Effective in patients refractory MI
to verapamil Atropine reduces AV node
ERP and increases
conduction velocity in bundle
Adenosine of His
ADRs: Dyspnoea, chest pain, Atropine I.M
hypotension, flushing, Drugs for AV block
cardiac arrest, bronchospasm Adrenaline, isoprenaline
Other uses: Increase AV conduction and
Diagnosis of AVN shorten ERP in conducting
tachycardia tissues
To induce brief coronary Used temporarily in partial
vasodilatation during and complete heart block till
diagnostic/interventional pacemaker can be implanted
procedures Any questions?
Controlled hypotension
THANK YOU

Antiarrhythmic Drugs

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Antiarrhythmic Drugs

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ANTIARRHYTHMIC DRUGS and propagates to the rest of

(AADs) the heart-PACEMAKER

Heart rate (increased/decreased) MECHANISMS OF

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