These are drugs that are used against arrhythmia and their mechanisms of actions

1. Antiarrhythmic Drugs

2. Rhythm
a regular, repeated pattern of sounds or movements.
Cardiac dysrhythmia
(also known as arrhythmia or irregular heartbeat)
is any of a group of conditions in which the electrical activity of the heart is irregular or
faster or slower than normal.
The heart beat may be:
Too fast (over 100 beats per minute).
Too slow (less than 60 beats per minute).
Regular or irregular.
A heart beat that is:
Too fast is called tachycardia.
Too slow is called bradycardia.
Antiarrhythmic agents
are a group of drugs that are used to suppress abnormal rhythms of the heart.

3. Cardiac
Electrophysiology

4. Properties of Cardiac Muscle
Autorhythmicity Excitability
Conductivity Contractility

5. The Conducting System
 The Nodal System
 Sinoatrial Node (S-A node) 1
 Atrioventricular Node (A-V node) 3
 The Internodal System
 Anterior, Middle & Posterior 2
 Bachmann`s bundle 7
 The Purkinje System
 Atrioventricular bundle (bundle of His) 4
 Right & left bundle branch 5
 Purkinje fibers 6

6. Normal conduction pathway:
1- SA node generates action
potential and delivers it to
the atria and the AV node
2- The AV node delivers the
impulse to purkinje fibers
3- purkinje fibers conduct the
impulse to the ventricles
Other types of
conduction that
occurs between
myocardial cells:
When a cell is
depolarized 
adjacent cell
depolarizes along

8. Pacemaker
SA-node
Primary pacemaker
105 impulse/min
Sinus rhythm
AV-node
Secondary pacemaker
45-60 impulse/min
Nodal rhythm
Purkinje System
Tertiary pacemaker
25-40 impulse/min
Idioventricular rhythm
Inhibitory vagal
tone

9. Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)
 Characteristics of Pacemaker Cells
 The membrane reach threshold potential (-40mV) by itself
 when the membrane potential is very negative (about -60 mV), ion
channels open that conduct slow, inward (depolarizing) Na+ currents.
These currents are called "funny" currents and abbreviated as "If".
 As the membrane potential reaches about -50 mV, another type of
channel opens. This channel is called transient or T-type Ca++ channel.
 When the membrane depolarizes to about -40 mV, a second type of
Ca++ channel opens. These are the so-called long-lasting, or L-type
Ca++ channels. Opening of these channels causes more Ca++ to enter
the cell and to further depolarize the cell until an action potential threshold
is reached.
 Repolarization occurs (Phase 3) as K+ channels open thereby increasing
the outward K+ currents. At the same time, the L-type Ca++ channels
become inactivated and close

10. Pacemaker AP
Phase 4: pacemaker
potential
Na influx and K efflux
and Ca influx until the
cell reaches threshold
and then turns into
phase 0
Phase 0: upstroke:
Due to Ca++ influx
Phase 3:
repolarization:
Due to K+ efflux
Pacemaker cells (automatic cells) have
unstable membrane potential so they can
generate AP spontaneously

11. Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)
 Characteristics of Pacemaker Cells
Pacemaker cells (automatic cells) have unstable membrane potential so they
can generate AP spontaneously

12. Myocardial Physiology
Contractile Cells
 Special aspects
 The action potential of a contractile cell
 Ca2+ plays a major role again
 Phases
4 – resting membrane potential @ -90mV
0 – depolarization
 Voltage gated Na+ channels open… close at 20mV
1 – temporary repolarization
 Open K+ channels allow some K+ to leave the cell
2 – plateau phase
 Voltage gated Ca2+ channels are fully open
3 – repolarization
 Ca2+ channels close and K+ permeability increases as more
activated K+ channels open, causing a quick repolarization
 What is the significance of the plateau phase?

13. Non-pacemaker action potential
Phase 0: fast
upstroke
Due to Na+
influx
Phase 3:
repolarization
Due to K+ efflux
Phase 4: resting
membrane potential
Phase 2: plateu
Due to Ca++
influx
Phase 1: partial
repolarization
Due to rapid efflux of K+
N.B. The slope of phase 0 = conduction velocity
Also the peak of phase 0 = Vmax

14. +30 mV
0 mV
-80 mV
-90 mV
OUTSIDE
MEMBRANE
INSIDE
Na+
0
4
3
2
1
K+
Ca++ K+ K+
Na+
K+
Ca++
Na+
K+
Na+
Resting
open
Inactivated
Phase zero
depolarization
Early
repolarization Plateau phase
Rapid
Repolarization
phase
Phase 4 Resting
membrane
potential

15. Myocardial Physiology
Contractile Cells

16. Effective and relative refractory periods
ERP RRP
ERP due to inactivated Na and Ca channels,
once they begin to recover the RRP begins.

17. The absolute refractory period
The absolute refractory period:
 During the absolute refractory period, the excitability level is 0%.
 No stimulus however strong can produce a propagated action potential
in the heart.
 This period begins with depolarization till mid-repolarization
 It lasts for the whole period of systole and the early part of diastole.

18. The relative refractory period
The relative refractory period:
 During the relative refractory period the excitability level is
more than 0 but less than 100% of the resting basal level.
 The heart responds only to stronger stimuli.
 It is a short period that begins at mid-repolarization and ends
shortly before complete repolarization.
 It lasts for a short period during diastole.

19. What is the Electrocardiogram?

21. ECG (EKG)
showing wave
segments
Contraction
of atria
Contraction of
ventricles
Repolarization of
ventricles
PR interval: represents
the rate of A-V
conduction
QS interval: represents
the duration of
ventricular systole

24. ANS Control of Heart
Cardiac Properties Parasympathetic (Vagal) Sympathetic
Supplies the atria, SA
node, AV node & AV
bundle but not the
ventricles
Supplies all cardiac
tissue including the
ventricles
Rhythmicity Slowing due to
depression of SA node
Acceleration due to ↑
of SA node
Excitability ↓ ↑
AV conduction ↓ (heart block) ↑
Contractility Depressed in atria Stimulated in atria
and ventricles
Rate of O2
consumption
↓ ↑

25. Arrhythmia
If the arrhythmia arises from the
ventricles it is called ventricular
arrhythmia
If the arrhythmia arises from
atria, SA node, or AV node it is
called supraventricular
arrhythmia
Causes of
arrhythmia
arteriosclerosis
Coronary artery
spasm
Heart block
Myocardial
ischemia

26. Mechanisms of Arrhythmogenesis
1- Abnormal impulse generation
Automatic rhythms Triggered rhythms
2-Abnormal conduction
Conduction block Reentry

27. Automatic rhythms
Enhanced normal
automaticity
Ectopic focus
↑AP from SA node
AP arises from sites other
than SA node

28. Ectopic foci
An ectopic focus is an area in the contractile myocardium, which
discharges electrical impulses.
Normally, the contractile myocardium has a stable resting
membrane potential
Under some non-physiological conditions, some myocardial cells
acquire rhythmic electrical activity and act as foci that send un-
timed electrical impulses or might even take over the heart and
act as the pacemaker.
 Factors that enhance automaticity include:
 SANS,  PANS,  CO2,  O2,  H+,  stretch, hypokalemia and hypocalcaemia.

29. Triggered rhythms
Delayed
afterdepolarization
Early
afterdepolarization
Triggered beats occur when problems at the level of the ion channels in
individual heart cells result in abnormal propagation of electrical activity and
can lead to sustained abnormal rhythm.
Early afterdepolarizations (EADs) occur
with abnormal depolarization during
phase 2 or phase 3, and are caused by
an increase in the frequency of abortive
action potentials before normal
repolarization is completed.
Before another action potential would
normally occur. Delayed afterdepolarizations
(DADs) begin during phase 4 - after
repolarization is completed

30. 2-Abnormal conduction
Conduction block
1st
degree
2nd
degree
3rd
degree
Reentry
This is when the
impulse is not
conducted from
the atria to the
ventricles

31. First-degree heart block – The electrical impulses are slowed as they pass
through the conduction system, but they all successfully reach the
ventricles.
Second-degree heart block– The electrical impulses are delayed further and
further with each heartbeat until a beat fails to reach to the ventricles entirely.
Third-degree heart block – With this condition, also called complete heart
block, none of the electrical impulses from the atria reach the ventricles.

32. Reentry
Circus
movement
Reflection
Re-entry is a common cause of arrhythmias.
Ventricular tachycardia and AV-nodal re-entry are typical
examples. Re-entry can occur when a conduction path is
partly slowed down.

34. Here is an accessory
pathway in the heart
called Bundle of Kent
•Present only in small populations
•Lead to reexcitation  Wolf-Parkinson-White
Syndrome (WPW)
Abnormal anatomic conduction
Wolff–Parkinson–White syndrome (WPW) is one of several disorders of
the conduction system of the heart. WPW is caused by the presence of an
abnormal accessory electrical conduction pathway between the atria and
the ventricles.
Electrical signals travelling down this abnormal pathway (known as the
bundle of Kent) may stimulate the ventricles to contract prematurely.

35. Bradyarrhythmias
THE SLOW POKES (HR<60)…

36. First Degree AV Block
 Delay at the AV node results in prolonged
PR interval
 PR interval>0.2 sec.
 Leave it alone

37. Second Degree AV Block Type
1 (Wenckebach)
 Increasing delay at AV node until a p wave is not
conducted.
 Often comes post inferior MI with AV node ischemia
 Gradual prolongation of the PR interval before a
skipped QRS. QRS are normal!
 No pacing as long as no bradycardia.

38. Second Degree AV Block Type
2
 Diseased bundle of HIS with BBB.
 Sudden loss of a QRS wave because p
wave was not transmitted beyond AV node.
QRS are abnormal!
 May be precursor to complete heart block
and needs pacing.

39. Third Degree AV Block
 Complete heart block where atria and
ventricles beat independently AND atria beat
faster than ventricles.
 Must treat with pacemaker.

40. Supraventricular Arrhythmias
 Sinus Tachycardia: high sinus rate of 100-180 beats/min, occurs during
exercise or other conditions that lead to increased SA nodal firing rate.
 Atrial Tachycardia: a series of 3 or more consecutive atrial premature beats
occurring at a frequency >100/min
 Paroxysmal Atrial Tachycardia (PAT): tachycardia which begins and
ends in acute manner.
 Atrial Flutter: sinus rate of 250-350 beats/min.
 Atrial Fibrillation: uncoordinated atrial depolarizations.
AV blocks
A conduction block within the AV node , occasionally in the bundle of His, that
impairs impulse conduction from the atria to the ventricles.
Types of Arrhythmia

41.  Ventricular Premature Beats (VPBs): caused by ectopic
ventricular foci; characterized by widened QRS.
 Ventricular Tachycardia (VT): high ventricular rate caused by
abnormal ventricular automaticity or by intraventricular reentry; can
be sustained or non-sustained (paroxysmal); characterized by
widened QRS; rates of 100 to 200 beats/min; life-threatening.
 Ventricular Flutter: ventricular depolarizations >200/min.
 Ventricular Fibrillation: uncoordinated ventricular depolarizations
Ventricular Arrhythmias

44. Pharmacologic Rationale & Goals
 The ultimate goal of antiarrhythmic drug therapy:
o Restore normal sinus rhythm and conduction
o Prevent more serious and possibly lethal arrhythmias from occurring.
 Antiarrhythmic drugs are used to:
 decrease conduction velocity
 change the duration of the effective refractory period (ERP)
 suppress abnormal automaticity

45. Antyarrhythmic drugs
class mechanism action notes
I Na+ channel blocker
Change the slope of
phase 0
Can abolish
tachyarrhythmia
caused by reentry
circuit
II β blocker
↓heart rate and
conduction velocity
Can indirectly alter K
and Ca conductance
III K+ channel blocker
1. ↑action potential
duration (APD) or
effective refractory
period (ERP).
2. Delay repolarization.
Inhibit reentry
tachycardia
IV Ca++ channel blocker
Slowing the rate of rise
in phase 4 of SA node
↓conduction velocity
in SA and AV node
•Most antiarrhythmic drugs are pro-arrhythmic (promote arrhythmia)
•They are classified according to Vaughan William into four classes according to their
effects on the cardiac action potential

46. Proarrhythmia is a new arrhythmias, paradoxically
precipitated by antiarrhythmic therapy, which means it is a
side effect associated with the administration of some
existing antiarrhythmic drugs, as well as drugs for other
indications.
In other words, it is a tendency of antiarrhythmic drugs to
facilitate emergence of new arrhythmias

47. Class I
IA IB IC
They ↓ conduction velocity in non-nodal
tissues (atria, ventricles, and purkinje fibers)
They act on open
Na+ channels or
inactivated only
Have moderate K+
channel blockade
So they are used
when many Na+
channels are opened
or inactivated (in
tachycardia only)
because in normal
rhythm the channels
will be at rest state
so the drugs won’t
work
Class I drugs

48.  Slowing of the rate of rise in phase 0 
↓conduction velocity
 ↓of Vmax of the cardiac action potential
 They prolong muscle action potential &
ventricular (ERP)
 They ↓ the slope of Phase 4 spontaneous
depolarization (SA node)  decrease
enhanced normal automaticity
Class IA
Quinidine Procainamide
They make the
slope more
horizontal

49. Class IA Drugs
 They possess intermediate rate of association and dissociation
(moderate effect) with sodium channels.
Pharmacokinetics:
procainamide
Good oral
bioavailability
Used as IV to
avoid
hypotension
quinidine
Good oral
bioavailability
Metabolized
in the liver
Procainamide metabolized into N-acetylprocainamide (NAPA) (active class
III) which is cleared by the kidney (avoid in renal failure)

50. Class IA Drugs Uses
 Quinidine is rarely used for supraventricular arrhythmias
 IV procainamide is used for acute conversion of atrial
fibrillation
 Oral quinidine/procainamide are used with class III drugs in
ventricular tachycardia
 IV procainamide used for hemodynamically stable
ventricular tachycardia

51. Class IA Drugs Toxicity
quinidine
AV block
Torsades de pointes
arrhythmia because it
↑ ERP (QT interval)
Shortens A-V nodal
refractoriness (↑AV
conduction) by
antimuscarinic like
effect
↑digoxin concentration
by :
1- displace from tissue
binding sites
2- ↓renal clearance
Ventricular
tachycardia
procainamide
Asystole or
ventricular
arrhythmia
Hypersensitivity : fever,
agranulocytosis
Systemic lupus erythromatosus (SLE)-like
symptoms: arthralgia, fever, pleural-
pericardial inflammation.
Symptoms are dose and time dependent
Common in patients with slow hepatic
acetylation

52. Systemic lupus erythematosus (also called lupus or SLE) is a
disease where a person's immune system attacks and injures
the body's own organs and tissues. Almost every system of
the body can be affected by SLE.
Arthralgia means joint pain. It is a combination of two Greek
words – Arthro – joint and algos – pain.
Agranulocytosis a failure of the bone marrow to make enough
white blood cells (neutrophils).

53. Notes:
Torsades de pointes: twisting of the point . Type of
tachycardia that gives special characteristics on ECG
At large doses of quinidine  cinchonism occurs:blurred vision, tinnitus, headache,
psychosis and gastrointestinal upset

54.  Both a defibrillator and a pacemaker are used in patient with heart
disease.
 A defibrillator is used to shock the heart when a patient goes into
cardiac arrest.
 A pacemaker is used to regulate abnormal heart rate or rhythm.

55. Class IB Drugs
 They shorten Phase 3
repolarization
 ↓ the duration of the cardiac
action potential
 They suppress arrhythmias
caused by abnormal automaticity
 They show rapid association &
dissociation (weak effect) with
Na+ channels with appreciable
degree of use-dependence
 No effect on conduction velocity
Class IB
lidocaine mexiletine tocainide

56. Agents of Class IB
Lidocaine
 Used IV because of extensive 1st
pass metabolism
 Lidocaine is the drug of choice in
emergency treatment of ventricular
arrhythmias
 Has CNS effects: drowsiness,
numbness, convulstion, and
nystagmus
Mexiletine
 These are the oral analogs of lidocaine
 Mexiletine is used for chronic
treatment of ventricular arrhythmias
associated with previous myocardial
infarction
Uses
They are used in the treatment of ventricular arrhythmias arising during myocardial
ischemia or due to digoxin toxicity
They have little effect on atrial or AV junction arrhythmias (because they don’t act on
conduction velocity)
Adverse effects:
1- neurological effects
2- negative inotropic activity

57. Class IC Drugs
 They markedly slow Phase 0 fast
depolarization
 They markedly slow conduction in
the myocardial tissue
 They possess slow rate of
association and dissociation
(strong effect) with sodium
channels
 They only have minor effects on
the duration of action potential
and refractoriness
Class IC
flecainide propafenone

58. Uses:
 Refractory ventricular arrhythmias.
 Flecainide is a particularly potent suppressant of premature ventricular
contractions (beats)
Toxicity and Cautions for Class IC Drugs:
 They are severe proarrhythmogenic drugs causing:
1. severe worsening of a preexisting arrhythmia
2. de novo occurrence of life-threatening ventricular tachycardia
 In patients with frequent premature ventricular contraction (PVC)
following MI, flecainide increased mortality compared to placebo.
Notice: Class 1C drugs are particularly of low safety and have
shown even increase mortality when used chronically after MI

59. Compare between class IA, IB, and IC drugs as
regards effect on Na+ channel & ERP
 Sodium channel blockade:
IC > IA > IB
 Increasing the ERP:
IA>IC>IB (lowered)
Because of
K+
blockade

60. Class II ANTIARRHYTHMIC DRUGS
(β-adrenergic blockers)
Mechanism of action
 Negative inotropic and
chronotropic action.
 Prolong AV conduction
(delay)
 Diminish phase 4
depolarization  suppressing
automaticity(of ectopic focus)
Uses
 Treatment of increased sympathetic
activity-induced arrhythmias such as
stress- and exercise-induced arrhythmias
 Atrial flutter and fibrillation.
 AV nodal tachycardia.
 Reduce mortality in post-myocardial
infarction patients
 Protection against sudden cardiac death

61. Class II ANTIARRHYTHMIC DRUGS
 Propranolol (nonselective): was proved to reduce the incidence of
sudden arrhythmatic death after myocardial infarction
 Metoprolol
 reduce the risk of bronchospasm
 Esmolol:
 Esmolol is a very short-acting β1-adrenergic blocker that is used by
intravenous route in acute arrhythmias occurring during surgery or
emergencies
selective

62. Class III ANTIARRHYTHMIC
DRUGS
K+ blockers
 Prolongation of phase 3
repolarization without altering
phase 0 upstroke or the resting
membrane potential
 They prolong both the duration of the action
potential and ERP
 Their mechanism of action is still not clear but
it is thought that they block potassium
channels

63. Uses:
 Ventricular arrhythmias, especially ventricular fibrillation or tachycardia
 Supra-ventricular tachycardia
 Amiodarone usage is limited due to its wide range of side effects
Class III
sotalol amiodarone ibutilide

64. Sotalol (Sotacor)
 Sotalol also prolongs the duration of action potential and
refractoriness in all cardiac tissues (by action of K+ blockade)
 Sotalol suppresses Phase 4 spontaneous depolarization and
possibly producing severe sinus bradycardia (by β blockade
action)
 The β-adrenergic blockade combined with prolonged action
potential duration may be of special efficacy in prevention of
sustained ventricular tachycardia
 It may induce the polymorphic torsades de pointes ventricular
tachycardia (because it increases ERP)
Ibutilide
Used in atrial fibrillation or flutter
IV administration
May lead to torsade de pointes
Only drug in class three that possess pure K+ blockade

65. Amiodarone (Cordarone)
 Amiodarone is a drug of multiple actions and is still not well understood
 It is extensively taken up by tissues, especially fatty tissues (extensive
distribution)
 t1/2 = 60 days
 Potent P450 inhibitor
 Amiodarone antiarrhythmic effect is complex comprising class I, II, III, and
IV actions
• Dominant effect: Prolongation of action potential duration and refractoriness
• It slows cardiac conduction, works as Ca2+ channel blocker, and as a weak β-
adrenergic blocker
Toxicity
 Most common include GI intolerance, tremors, ataxia, dizziness, and hyper-or
hypothyrodism
 Corneal microdeposits may be accompanied with disturbed night vision
 Others: liver toxicity, photosensitivity, gray facial discoloration, neuropathy,
muscle weakness, and weight loss
 The most dangerous side effect is pulmonary fibrosis which occurs in 2-
5% of the patients

66. Class IV ANTIARRHYTHMIC
DRUGS
(Calcium Channel Blockers)
 Calcium channel blockers decrease inward Ca2+
currents resulting in a decrease of phase 4
spontaneous depolarization (SA node)
 They slow conductance in Ca2+ current-dependent
tissues like AV node.
 Examples: verapamil & diltiazem
Because they act on the heart only and not on blood
vessels.
 Dihydropyridine family are not used
because they only act on blood vessels

67. Mechanism of
action
 They bind only to depolarized (open) channels  prevention of repolarization
 They prolong ERP of AV node  ↓conduction of impulses from the atria to the ventricles
So they act only in cases of arrhythmia because many Ca2+
channels are depolarized while in normal rhythm many of them
are at rest
More effective in treatment of atrial than ventricular arrhythmias.
Treatment of supra-ventricular tachycardia preventing the
occurrence of ventricular arrhythmias
Treatment of atrial flutter and fibrillation
Uses

68. contraindication
 Contraindicated in patients with pre-existing depressed heart function
because of their negative inotropic activity
Adverse effects
 Cause bradycardia, and asystole especially when given in combination
with β-adrenergic blockers

69. Miscellaneous Antiarrhythmic Drugs
Adenosine
o Adenosine activates A1-purinergic receptors decreasing the SA
nodal firing and automaticity, reducing conduction velocity,
prolonging effective refractory period, and depressing AV nodal
conductivity
o It is the drug of choice in the treatment of paroxysmal supra-
ventricular tachycardia
o It is used only by slow intravenous bolus
o It only has a low-profile toxicity (lead to bronchospasm) being
extremly short acting for 15 seconds only

70. Magnesium indications.
 1. Torsades de point from any reason.
 2. Arrhythmias in a patient with known
hypomagnesaemia.
 3. Consider its use in acute ischaemia to prevent
early ventricular arrhythmias.
 4. Digoxin induced arrhythmias.

71.  A. Digoxin
 Digoxin [di-JOX-in] shortens the refractory period in atrial and ventricular
myocardial cells while prolonging the effective refractory period and
diminishing conduction velocity in the AV node.
 Digoxin is used to control the ventricular response rate in atrial fibrillation
and flutter. At toxic concentrations, digoxin causes ectopic ventricular beats
that may result in ventricular tachycardia and fibrillation.
 [Note: This arrhythmia is usually treated with lidocaine or phenytoin.]

72. class ECG QT Conduction
velocity
Refractory
period
IA ++ ↓ ↑
IB 0 no ↓
IC + ↓ no
II 0 ↓In SAN and
AVN
↑ in SAN and
AVN
III ++ No ↑
IV 0 ↓ in SAN and
AVN
↑ in SAN and
AVN

74. 1st: Reduce thrombus formation by using anticoagulant warfarin
2nd: Prevent the arrhythmia from converting to ventricular arrhythmia:
First choice: class II drugs:
•After MI or surgery
•Avoid in case of heart failure
Second choice: class IV
Third choice: digoxin
•Only in heart failure of left ventricular dysfunction
3rd: Conversion of the arrhythmia into normal sinus rhythm:
Class III:
IV ibutilide, IV/oral amiodarone, or oral sotalol
Class IA:
Oral quinidine + digoxin (or any drug from the 2nd step)
Class IC:
Oral propaphenone or IV/oral flecainide
Use direct current in case
of unstable hemodynamic
patient

76. First choice: class II
•IV followed by oral
•Early after MI
Second choice: amiodarone
Avoid using
class IC after
MI  ↑
mortality
First choice: Lidocaine IV
•Repeat injection
Second choice: procainamide IV
•Adjust the dose in case of renal failure
Third choice: class III drugs
•Especially amiodarone and sotalol
Premature ventricular beat (PVB)

78. Recommendations for focal Atrial
Tachycardia

81. ‫تجميعات‬
:
(IA, IC, class III)  torsades de pointes.
Classes II and IV  bradycardia (don’t combine the two)
In atrial flutter use (1st ↓impulses from atria to ventricular to prevent
ventricular tachycardia)
1. Class II
2. Class IV
3. Digoxin.
(
‫الترتيب‬ ‫على‬
)
2nd convert atrial flutter to normal sinus rhythm use:
1. Ibutilide
2. Sotalol
3. IA or IC.
(
‫الترتيب‬ ‫على‬
)
If you use quinidine combine it with digoxin or β blocker (because of its anti
muscarinic effect)
Avoid IC in myocardial infarction because it ↑ mortality

82.  Vernakalant
 Ajmaline
 Pilsicainide
 Ranolazine