1. ANTIARRHYTHMIC DRUGS
Dr. Kunal A. Chitnis
1st Year Resident
TNMC, Mumbai
17th September 2010

2. SA Node fires at 60-100 beats/sec
Spreads through atria
Enters the AV Node
(Delay of 0.15 sec)
Propagates through His Purkinje
system
Depolarizes ventricles beginning
from endocardial surface of apex to
epicardial surface of base
Normal Sinus Rhythm

3. Movement of ions across cell
membrane
• Ions move across in response to electrical and
concentration gradients
• Pass through specific ion channels or transporters
• The Equilibrium/Reversal potential is given by the
Nerst equation:
Eion= - 61Log(Ci/Ce)

4. • The Resting Membrane Potential of the
cell is -95mV
• The cell maintain this transmembrane
ionic gradient by
1. Active mechanisms like the Na+ pump
and Na+/K+ ATPase (Electrogenic)
2. Fixed anionic charges within the cell

5. No Net
movement
Net movement
inside the cell
EK -94 ENa +65

6. Phase 0:
RapidDepolarisation
(Na+ influx)
Phase 1:
Early Repolarisation
(Inward Na+ current
deactivated,
Outflow of K+):
Transient Outward Current
Phase 2:
Plateau Phase
(Slow inward Ca2+ Current balanced by
outward delayed rectifier K+ Current)
Phase 3:
Late Repolarisation
(Ca 2+current inactivates,
K+ outflow)
Action Potential of Cardiac Muscle

8. Action Potential of SA Node
 RMP not stable and full
repolarisation at -60mV
 Spontaneous
Depolarisation occurs due
to:
• Slow, inward Ca2+ currents
• Slow, inward Na+ currents
called “Funny Currents”
-50mV T-type
Ca2+ channels
-40mV L-type
Ca2+ channels
-35mV
Phase 3:
Repolarisation

9. Action Potential in AV Node
• Very similar to SA Node
• Causes delay of
conduction
• It gives time for atrial
contraction and filling of
the ventricles.
• Site of action of many
antiarrhythmics

10. Regulation by autonomic tone
Parasympathetic/Vagus Nerve
stimulation:
• Ach binds to M receptors, releasing G
protein βγ subunits
• Activate Ach dependent K+ current
• ↓ slope of Phase 4
Sympathetic stimulation:
• Activation of β1 receptors
• Augmentation of L-type Ca2+ current
and funny currents
• ↑ slope of Phase 4

12. Refractoriness
• Effective/Absolute Refractory period: During this
period, depolarization on adjacent cardiac muscles does
not produce a new depolarization.
• Protective mechanism and keeps the heart rate in check,
prevents arrhythmias and coordinates muscle
contraction

13. • During the plateau phase, max Na+ channels are
in inactivated state, therefore refractory
• Upon repolarisation, recovery occurs from the
inactivation state to closed state
• Only channels in closed state can be depolarised
• It extends from phase 0 uptill sufficient recovery
of Na channels.
• Changes in the ERP:
1. Altered recovery from inactivation
2. Action Potential Duration alteration

14. ERP of Fast responsive
tissue
• Dependent on Na+ channels
recovery
• Voltage dependent
ERP of Slow Responsive/
Nodal tissue
• Dependent on Ca2+ channels
recovery
• Time dependent/ decremental
response

15. Cardiac
Arrhythmias

16. Arrhythmia means an Abnormal heart
rhythm
Results from the abnormalities of:
 Impulse generation (Rate or Site of origin)
 Conduction
 Both

17. Classification of Arrhythmias
1. Characteristics:
a. Flutter – very rapid but regular contractions
b. Tachycardia – increased rate
c. Bradycardia – decreased rate
d. Fibrillation – disorganized contractile activity
2. Sites involved:
a. Ventricular
b. Atrial
c. SA Node
d. AV Node
Supraventricular

18. Mechanisms of Cardiac Arrhythmias
(A) Enhanced Automaticity:
• In cells which normally display spontaneous
diastolic depolarization (SA Node, AV Node, His-
Purkinje System)
• Automatic behavior in sites that ordinarily lack
pacemaker activity

19. A normal cardiac action potential may be
interrupted or followed by an abnormal
depolarization
Reaches threshold & causes secondary upstrokes
2 Major forms:
1. Early Afterdepolarization
2. Late Afterdepolarization
(B) Afterdepolarization and Triggered
Automaticity

20. 1. Early
Afterdepolarization
•Phase 3 of repolarization
interrupted
•Result from inhibition of Delayed
Rectifier K+ Current
•Marked prolongation of Action
Potential
•Slow heart rate, ↓ Extracellular K+,
Drugs prolonging APD

21. 2. Late
Afterdepolarizations
•Secondary deflection after
attaining RMP
•Intracellular Ca2+ overload
•Adrenergic stress, digitalis
intoxication, ischemia-reperfusion

22. (C) Re-entrant Arrhythmia
Defined as circulation of an
activation wave around an
inexitable object
3 requirements for Re-entrant
Arrhythmia:
1. Obstacle to conduction
2. Unidirectional block
3. CT>ERP

23. Unidirectional
Block
Establishment of Re-entrant circuit

24. Requirement to treat an arrhythmia:
1. ↓ CO:
• Slow contractions (bradyarrhythmias)
• Fast contractions (tachyarrhythmias)
• Asynchronous contractions (V Tach, V Fib)
2. Convert to serious Arrhythmias:
• Afl → VTach, V Tach → VF
3. Thrombus formation:
• AF→ Stasis in Atrium→ Thrombus formation→ Embolism

25. Management Of
Arrhythmias

26. Management
• Acute Management
• Prophylaxis
• Non Pharmacological
• Pharmacological

27. Non Pharmacological
• Acute
1. Vagal Maneuvers
2. DC Cardioversion
• Prophylaxis
1. Radiofrequency Ablation
2. Implantable Defibrillator
• Pacing (Temporary/ Permanent)

28. Pharmacological Approach
Drugs may be antiarrhythmic by:
• Suppressing the initiator mechanism
• Altering the re-entrant circuit
1. Terminate an ongoing arrhythmia
2. Prevent an arrhythmia

29. Drugs may ↓ automatic rhythms by altering:
A. ↓ Phase 4 slope
B. ↑ Threshold potential
C. ↑ Max diastolic potential
D. ↑ Action Potential Duration

30. Vaughan Williams Classification
Phase 4
Phase 0
Phase 1
Phase 2
Phase 3
0 mV
-
80m
V
II
I
III
IV
Class I: block Na+ channels
Ia (quinidine, procainamide,
disopyramide) (1-10s)
Ib (lignocaine) (<1s)
Ic (flecainide) (>10s)
Class II: ß-adrenoceptor
antagonists (atenolol, sotalol)
Class III: block K+ channels
(amiodarone, dofetilide,sotalol)
Class IV: Ca2+ channel
antagonists (verapamil, diltiazem)

31. Class I: Na+ Channel Blockers
• IA: Ʈrecovery moderate (1-10sec)
Prolong APD
• IB: Ʈrecovery fast (<1sec)
Shorten APD
• IC: Ʈrecovery slow(>10sec)
Minimal effect on APDTrecovery is time required to complete
approximately 63% of an exponentially
determined process to complete

32. Effect of Na+ channel
block on ERP:
The point at which sufficient
no. (25%) of Na+ channels
recovered from inactivation is
prolonged.
↑ ERP thus blocking early
extrasystoles
At times, post repolarization
refractoriness.
Drug

33. State Dependent Block of Na+ channels
• Na+ channel blockers
binds to channels in open
&/or inactivated state,
poorly/ not at all to resting
state
• Dissociate during
diastole
• Results in phasic
changes in extent of block
during AP

34. Effect of increased heart rate on the
Na+ channel block
↑ Na+ channel block as time spent in diastole ↓→↑ERP

35. Drugs having ↓ Rate of Recovery
Slow dissociation Rate→ ↑ Na+ Channel block→ ↑ ERP

36. Effect of RMP on Na+ channel Block
• At RMP of -85mV: block
is rapidly reversed during
diastole
• As RMP↑ : more no. of
channels remain in
inactivated state→↑ block
• Marked drug binding,
conduction block & loss of
excitability. Thus sick
tissue is selectively
inhibited

37. Ectopic
Pacemaker
↓ Upstroke
↑ Threshold↓ Slope phase 4
Block INa
Vm
(mV)
-80mV
0mV

38. Effect on Re-entrant Arrhythmia
Effect of Class I drugs:
1. ↓ Vmax: Extinguishing
of propagating re-
entrant wavefront
2. ↑ERP: CT<ERP

39. Ia Ib Ic
Moderate Na+ channel
blockade
Mild Na+ channel
blockade
Marked Na+ channel
blockade
Slow rate of rise of
Phase 0
Limited effect on
Phase 0
Markedly reduces rate
of rise of phase 0
Prolong refractoriness
by blocking several
types of K+ channels
Little effect on
refractoriness as there
is minimal effect on K+
channels
Prolong refractoriness
by blocking delayed
rectifier K+ channels
Lengthen APD &
repolarization
Shorten APD &
repolarization
No effect on APD &
repolarization
Prolong PR, QRS &
QT
QT unaltered or
slightly shortened
Markedly prolong PR
& QRS

40. Procainamide (Class Ia)
• Blocks open Na+ channels & Non specific blockade of K+
channels
• Ganglion blocking properties, thus can cause hypotension on iv
use
• Risk of excessive prolongation of QT interval & torsades de
pointes
• Drug induced Lupus Syndrome
• N-acetylprocainamide (NAPA) an active metabolite has class III
activity

41. • NAPA causes APD prolongation but no drug induced
lupus
• Fast acetylators: QT prolongation common
Slow acetylators: Drug induced Lupus common
• Effective in most atrial & ventricular arrhythmias

42. Quinidine (Class Ia)
• Diastereomer of antimalarial quinine
• Similar to procainamide
• Cardiac antimuscarinic (vagolytic)
• Risk of torsades due to QT prolongation
• Nausea, diarrhoea, vomiting, cinchonism
(headache, dizziness & tinnitus)

43. Disopyramide (Class Ia)
• Cardiac antimuscarinic effects more marked
than quinidine (blurred vision, dry mouth, urinary
retention)
• Risk of torsades
• Maintain sinus rhythm in AF/Afl
• To prevent VTach/VF

44. Lidocaine (Class Ib)
• Highly effective in arrhythmias associated with AMI
• Blocks activated & inactivated Na+ channels with rapid
kinetics
• The inactivated channel block ensures greater effects on
cells with long action potentials like purkinje fibres &
ventricular cells
• Selective depression in depolarized &/or rapidly driven
cells

45. • S/E Seizures, tremors, dysarthria, altered consciouness,
nystagmus
• Action terminated by rapid redistribution (t1/2 8mins) &
hepatic metabolism(t1/2120mins)
• Given only i.v.
• Termination of ventricular arrhythmias, prevention VF
after cardioversion

46. Mexiletine (Class Ib)
• Orally acting congener of Lidocaine
• Electrophysiological & antiarrhythmic actions
similar to Lidocaine
• Other uses: Relieving pain due to diabetic
neuropathy & nerve injury

47. Flecainde (Class Ic)
• Potent blocker of Na+ & K+ channels with slow
unblocking kinetics
• Blocks K+ channels but does not prolong APD & QT
interval
• Maintain sinus rhythm in supraventricular
arrhythmias
Cardiac Arrhythmia Suppression Test (CAST Trial):
When Flecainide & other Class Ic given
prophylactically to patients convalescing from
Myocardial Infarction it increased mortality by 21/2 fold.
Therefore the trial had to be prematurely terminated

48. Propafenone (Class Ic)
• Properties similar to flecainide
• Weak β blocking activity
• Used for supraventricular arrhythmias

49. Moricizine (Class Ic)
• Phenothiazine analogue
• Chronic treatment of ventricular arrhythmias
CAST II
 Increased mortality shortly after a myocardial
infarction & did not improve survival during long
term therapy

50. Class II: β Adrenoreceptor
Blocking Drugs

51. β Adrenergic Stimulation β Blockers
↑ magnitude of Ca2+ current & slows
its inactivation
↓ Intracellular Ca2+ overload
↑ Pacemaker current→↑ heart rate ↓Pacemaker current→↓ heart rate
↑ DAD & EAD mediated arrhythmias Inhibits after-depolarization mediated
automaticity
Epinephrine induces hypokalemia (β2
action)
Propranolol blocks this action

52. Other Actions:
• ↑ AV Nodal conduction time & prolong its
refractoriness (↑PR interval)
Useful in re-entrant arrhythmias involving AV node
& controlling ventricular response in Afl/AF
• Controlling arrhythmias associated with physical
or emotional stress
(blocking β mediated actions of catecholamines)

53. • Clinical trials suggest that they
significantly reduce incidence of re-
infarction & sudden death after an MI
↓ Size of infarct & arhhythmias
Increase energy required to defibrillate the
heart
↓ chances of subsequent MI
• Includes Propranolol, Esmolol, Timolol,
Metoprolol, Atenolol, Bisoprolol

54. Selected β Adrenergic Receptor blockers
Propranolol:
• Exert Na+ channel blocking (membrane stabilizing)
effects at high concentrations
• Clinical significance is unknown
Acebutolol:
• Suppresses ventricular ectopics
Esmolol:
• β1 selective metabolized by RBC esterases
• t1/2 9 mins
• Rate control of rapidly conducted AF

55. Class III: K+ Channel
Blockers

56.  Prolong action potential by blocking K+ currents
usually Ikr
 Enhance inward current also through Na+
channels
 Prolong Repolarization→ QT Prolongation
 Thereby ↓ Automaticity & inhibit Re-entry
(↑ ERP)
 Other actions: ↓ Defibrillation energy
requirement, ↑ contractility & inhibition of VF owing
to ischemia

57. Vm
(mV)
-80mV
0mV
↑ APD
Ectopic
Pacemaker
Block IK

58. Reverse Use Dependence:
Action potential prolongation is least marked
at fast rates & most marked at slow rates
Thus risk of torsades
Toxicity:
These drugs have a risk of torsades as they
prolong cardiac action potential
More common in women

59. Amiodarone
• Blocks variety of channels: IKr , IKs , IKto , IKir
• Also blocks inactivated Na channels, ↓Ca current,
adrenergic blocker
• Thus Class I,II,III,IV effects
•↓abnormal automaticity, prolongs APD,
↓ conduction velocity

60. PK:
• Oral bioavailability 30%
• Distributed in lipids
• Undergoes hepatic metabolism by CYP3A4 to
desethyl-amiodarone (active metabolite)
• Effect maintained over 1-3 months after
discontinuation

61. Adverse effects:
• Hypotention
• Torsades
• Pulmonary fibrosis (CXR, PFT)
• Corneal microdeposits
• Hypo/hyper thyroidism
• Peripheral neuropathy, proximal weakness
• Photosensitivity
• Hepatic dysfunction

62. Uses
• Oral→ chronic arrhythmias, iv→acute life
threatening arrhythmias
• Prevention of Recurrent VTach/VF
• Maintain sinus rhythm in AF
• Acute termination of VTach/VF
• Wolf-Parkinson-White syndrome

63. Dronedarone
• Structural analogue of amiodarone without iodine
• Blocks IKr, IKs, ICa, INa & β receptors
• No thyroid & pulmonary toxicity
• Maintain sinus rhythm in paroxysmal/persistent
AF/Afl

64. Dofelitide
• Potent & Pure IKr blocker
• Slow rate of recovery
• PK: 100% bioavailability, excreted unchanged by
kidneys
• S/E: torsades viz dose dependent
• Used to maintain sinus rhythm in AF/Afl

65. Ibutilide
• IKr blocker & activates INa
• Rapid iv infusion used for immediate conversion of
Afl/AF to sinus rhythm
• Efficacy Afl>AF
• PK: undergoes extensive 1st pass metabolism.
Thus not used orally. t1/2 6hrs
• S/E: torsades

66. Sotalol
• IKr blocker and non selective β receptor blocker
• Class II,III actions
• ↑ APD, ↓ automaticity, slows AV Nodal conduction
& prolong AV Nodal refractoriness
• Prolongs QT interval
• S/E: EAD‟s & torsades

67. • PK: 100% bioavailable, excreted unchanged in
urine
• Uses:
Ventricular arrhythmias, maintenance of sinus
rhythm AF, used in pediatric age-group

68. Vernakalant (RSD1235)
• Investigational multichannel ion blocker
• Blocks IKr, IKur, IKAch, Ito
Thus prolong atrial repolarization & ERP.
Less action potential prolongaton in ventricle
• Rate dependent Na channel block (Recovery is
fast)
• Slows conduction of AV node

69. • S/E: dysgeusia, cough, paraesthesia,
hypotension
• PK: metabolized in liver by CYP2D6, t1/2 2hrs
• Use: Converting recent onset AF to sinus rhythm

70. Class IV: Ca2+ Channel
Blocking Drugs

71. • Block L-Type Ca 2+ channels in slow-
response tissues & depress Phase 3 & 4
• Slows SA Node by its direct action
• AV Node conduction time & effective
refractive period increased (Prolongs PR
interval)
• Important effect on upper & middle parts of
AV Node

72. • Shorten plateau of action potential &
reduce force of contraction
• Suppress both Early & Late Depolarization
• May have a particular value in blocking
one limb of re-entry circuit

73. His Bundle
Normal ERP
Premature
Atrial Beat
Atrium
“Dispersion of
Refractoriness”
Normal ERP
β
Ischemic Area
Long ERP
PSVT:
•140-220 min -1
• sudden onset
• palpitations,dizziness
AV Node Re-entry

74. Ischemic Area
Verapamil/
Diltiazem
Normal ERP
Long ERP
β
Long ERP
ERP>CT
Effect of ClassIV Drugs on AV Nodal
Reentrant Arrhythmia

75. • Parental verapamil & diltiazem approved for
rapid conversion of PSVT to sinus rhythm &
temporary control of rapid ventricular rate in AF/Afl
• C/I in WPW syndrome
• Oral verapamil in conjugation with digoxin to
control ventricular rate in chronic AF/AFl

76. Verapamil
• Blocks both activated & inactivated Ca2+
channels
• Given orally with a t1/2 8hrs
• extended release formulation available
• If used with digoxin, then dose is reduced
• S/E constipation, lassitude, peripheral edema

77. Diltiazem
• Similar in efficacy to verapamil
• Undergoes a high first pass metabolism
• Relatively more smooth muscle relaxing action

78. Miscellaneous

79. Adenosine
• Naturally occurring nucleoside
• Acts on specific G protein-coupled adenosine receptors
• Activates IKAch channels in SA node, AV node & Atrium
Shortens APD, hyperpolarization & ↓ automaticity
• Inhibits effects of ↑ cAMP with sympathetic stimulation
↓ Ca currents
↑AV Nodal refractoriness & inhibit DAD‟s

80. Vm
(mV)
-80mV
0mV
↓ APD
Hyperpolarization
Adenosine

81. PK:
• Carrier mediated uptake & metabolism by
deaminase in most cells
• t1/2 few seconds
• Given as iv bolus
• Theophylline & caffeine→ block adenosine
receptors

82. Adverse effects:
• flushing, shortness of breath, chest burn
Use:
• DOC for acute termination of re-entrant
supraventricular arrhythmia
•Rare cases of DAD mediated VTach

83. Digitalis
• Acts by blocking Na+/K+ATPase→ +ve Inotropic effect
• Antiarrhythmic actions exerted by AV Nodal Refractoriness
by:
Vagotonic actions→ inhibit Ca2+ currents in AV node
• Activation of IKAch in atrium: hyperpolarization & shortening
of APD in atria
• ↑ Phase 4 slope→ ↑ Rate of automaticity in ectopic
pacemakers

84. • ECG: PR prolongation, ST segment depession
• Adverse Effects:
 Non cardiac: Nausea, disturbance of cognition,
yellow vision
 Cardiac: Digitalis induced arrhythmias
• PK: Digoxin- 20-30% protein bound, slow
distribution to effector sites, loading dose given,
t1/2 36hrs, renal elimination

85. Digitoxin- hepatic metabolism, highly protein
bound, t1/2 7days
Toxicity results with amiodarone & quindine
(↓ clearance) Thus dose has to be decreased
• Used in terminating re-entrant arrhythmia
involving AV Node & controlling ventricular
rate in AF

86. Magnesium
• Its mechanism of action is unknown but may
influence Na+/K+ATPase, Na+ channels, certain
K+ channels & Ca2+ channels
• Digitalis induced arrhythmias if
hypomagnesemia present
• Torsade de pointes even if serum Mg2+ is
normal
• Given 1g over 20mins

90. Bradyarrhythmias
Resting heart rate of <60/min
Classified as Atrial/AV Nodal/Ventricular
Management:
• Acute→ iv atropine
• Permanent→ Pacemakers

91. Toxicities

92. Class I
Conduction slowing can account for toxicity
Afl 300/min
Slowing of conduction with Na+ channel blocker
AV Node permits greater no of impulses
(Drop in Afl 300/min with 2:1 or 4:1 AV conduction
to 220/min with 1:1 conduction HR 220beats/min)

93. • Re-entrant VTach after MI can ↑ frequency &
severity arrhythmic episodes
• Slowed conduction allows the re-entrant wave
front to persist within tachycardia circuit
• Difficult to treat
• Na+ infusion may be beneficial

94. Class II
• Bradycardia & exacerbation of CCF in patients
with low ejection fraction
Class Ia & Class III
• Excessive QT prolongation & torsades de
pointes
• „„Twisting of points”

95. • Rapid, polymorphic ventricular tachycardia
•Twist of the QRS complex around the
isoelectric baseline
• Fall in arterial blood pressure
• Can degenerate into Ventricular fibrillation

96. Treatment:
• Withdrawal of offending drug
•Magnesium sulphate
•Phenytoin
•Isoproterenol infusion/Pacing
•Defibrillation

97. Digitalis Induced Arrhythmias
• Can cause virtually any arrhythmia
• DAD related tachycardia with impairment of
SAN & AVN
• Atrial tachycardia with AV block is classic
• Ventricular bigeminy
• Bidirectional ventricular tachycardia
• AV junctional tachycardia
• Various degrees of AV block
• Sever intoxication: Severe bradycardia with
hyperkalemia

98. Treatment
• Sinus bradycardia & AV block: Atropine
• Digitalis induced tachycardia responds to Mg2+
• Antidigoxin (DIGIBIND) binds to digoxin &
digitoxin thereby enhancing their renal excretion
• SA & Node AV Node dysfunction may require
temporary pacing

99. TRIALS
• Cardiac Arrhythmia Suppression Trial (CAST)
• Cardiac Arrhythmia Pilot Study (CAPS)
• Antiarrhythmics Versus Implantable Defibrillators (AVID)
• Atrial Fibrillation Follow-Up Investigation of Rhythm
Management (AFFIRM)

100. Therapeutic Drug Monitoring
• Important as these drugs have narrow therapeutic index
• Class IA & Digoxin- Most important for drug monitoring
• Amiodarone- TDM has limited role
• TDM less important for Class II, III & IV drugs
• TDM no value for Lignocaine & Procainamide due to
Active metabolites (GX, MEGX & NAPA)

101. Evaluation of Antiarrhythmic Drug Action
 Ex-Vivo Models:
• Guinea pig muscle strips
In-Vivo Models:
• Atrial Arrhythmias
1. Atrial Rapid Pacing Model
2. Afl with Anatomical Obstacle Model

102. • Ventricular Arrhythmias
1. Digitalis-induced Ventricular Arrhythmia
2. Halothane adrenaline Arrhythmia
3. Canine two stage coronary ligation Arrhythmia
4. Programmed electrical stimulation induced re-entry Arrhythmia
5. Coronary artery occlusion/reperfusion Arrhythmia
• Genetic Models:
1. Homozygous null connexin 40 vulnerability to atrial
arrhythmias
2. Transgenic mouse model→ Over expresses a constitutively
active form of TGF-b1

103. Clinical Evaluation:
Two designs commonly used:
1. Evaluating antiarrhythmic agents in pts with ICD
Outcome parameter – number of defibrillator discharge
2. Evaluating antiarrhythmic agents in target population
Mortality rates could be assessed
Large sample size required

104. Newer Advances

105. ZP123-Rotigaptide
• Prevents uncoupling of connexin 43 mediated gap
junction communication during acute metabolic stress
• Selective for atrial electrophysiology
• ↓ AF vulnerability in MR
Tedisamil
• Class III antiarrhythmic
• Blocks Ito, IKATP, IKr, IKs, IKur
• Prolongs APD atria>ventricles
• Could be used for AF, Afl

106. Azimilide
• Class III antiarrhythmic
• Blocks IKr & IKs
• Converts and maintains sinus rhythm in patients with
atrial arrhythmias
• Reduces frequency and severity of ventricular
arrhythmias in patients with implanted cardioverter-
defibrillators
AVE0118
• Blocks IKur & Ito
• Prolongs atria ERP
• May be useful in atrial arrhythmis

107. AZD 7009
• Inhibition of IKr, Ito, IKur and INa, a mixed ion channel
blockade
• Promising drug for converting AF to sinus rhythm
• Phase II trial
AP-792
• Cardioselective Ca2+ channel blocker
• Suppresses the ventricular arrhythmias
Encainide (MJ9067)
• Probably has effects on Phase 2
• Can be effective in suppressing ventricular ectopics

108. BRL32872
• Blocks IKr & L-type Ca2+ channels
• Prolongs APD
• May possibly prevent torsades de pointes
Piboserod
• Functional 5-HT4 receptor antagonist
• Could be used for AF
Nifekalant
• Class III antiarrhythmic
• Blocks IKr
• Approved in Japan
• Ventricular tachycardia

109. Conclusion
• Precipitating factors (ischemia, electrolyte imbalance,
drugs) should be eliminated
• Drugs acting on particular mechanism of arrhythmia
should be used
• Some arrhythmias should not be treated
• Risk benefit ratio assessed (drug provoked
arrhythmias)
• Patient specific contraindications (disopyramide→CCF,
amiodarone→pulmonary disease)