This document discusses antiarrhythmic drugs used to treat arrhythmias. It begins by defining arrhythmias as abnormalities in heart rate, rhythm or conduction. It then discusses the normal physiology of the heart including the properties of cardiac muscle cells and the conduction system. It explains the mechanisms of arrhythmias and classification of antiarrhythmic drugs. The major classes of antiarrhythmic drugs are discussed in detail including mechanisms of action, indications, dosages and side effects. Class I drugs block sodium channels, Class II are beta blockers, and Class III block potassium channels.

1. ANTIARRHYTHMIC DRUGS

2. ARRHYTHMIA
 ABNORMALITY IN THE ORIGIN, RATE, RHYTHM,
CONDUCTION VELOCITY AND SEQUENCE OF HEART
ACTIVATION.
 IT MAY CAUSE SUDDEN DEATH OR SYNCOPE, HEART
FAILURE, DIZZINESS, PALPITATIONS, OR NO
SYMPTOMS AT ALL.

3. Normal Physiology of Heart
The cardiac muscles are specialized
tissue with unique properties like
excitability, contractility and
automaticity
The myocardium has 2 types of
cells, contracting and conducting
cell.
The contracting cells participate in
the pumping action of the heart,
and they have the characteristic
property of Automaticity.

4. Automaticity is the ability of the cell to generate electrical impulses
spontaneously.
SA, AV and His-purkinje system comprises the conduction tissue
system of heart. Normally the SA node act as a pace maker of the
heart.
Excitability is the ability of the cell to undergo depolarization in
response to a stimulus.
Contractility is the ability of the myocardium to adequately contract
and pump the blood out of the heart.

5. +30 mV
0 mV
-80 mV
-90 mV
OUTSIDE
MEMBRANE
INSIDE
Na+
0
4
3
2
1
K+
Ca++ K+
Atp
K+
Na+
K+
Ca++
Na+
K+
Na+
Resting
open
Inactivated
Phase zero
depolarization
Early
repolarization Plateau phase
Rapid
Repolarization
phase
Phase 4
depolarization

6. Phase 0: rapid depolarization of cell membrane during which there is fast
entry of Na ions into the cells through Na channels, this is followed by
repolarization.
Phase 1: is short initial rapid repolarization due to K efflux
Phase 2:prolonged plateau phase due to slow Ca influx
Phases 3: rapid repolarization with K efflux
Phase 4: resting phase during which Ka ions return into the cell while Na
and Ka move out of it and resting membrane potential is stored

7. Mechanism of Arrhythmias
Abnormal heart pulse
formation
Sinus pulse
Ectopic pulse
Triggered activity
Abnormal heart pulse
Reentry
Conduction block

9. Classification based on
clinical use
Drugs used for supraventricular arrhythmia`s
◦ Adenosine, verapamil, diltiazem
Drugs used for ventricular arrhythmias
◦ Lignocaine, mexelitine, bretylium
Drugs used for supraventricular as well as ventricular arrhythmias
◦ Amiodarone, - blockers, disopyramide, procainamide

10. 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)
Class V : Miscellaneous.

11. CLASS I ANTI ARRHYTHMIC DRUGS

12.  It is largest class of Anti arrhythmic drugs.
 Class I anti arrhythmic drugs act by blocking voltage-sensitive sodium
(Na+) channels. These drugs bind to sodium channels when the
channels are open and in activated state and dissociate when the
channels are in resting phase.
 Inhibition of sodium channel decrease rate of rise of phase 0 of
cardiac membrane action potential and a slowing of conduction
velocity.
 They also block K channels (class IA) thus, slows the repolarization in
ventricular tissue.
 These drugs have local anesthetic activity and may suppress
myocardial contractile force, these affects are observed at a higher
plasma concentration.

14. USE DEPENDENCE:
Class I drugs bind more rapidly to open or inactivated sodium channels
than to channels that are fully repolarized following recovery from the
previous depolarization cycle.
 Therefore, these drugs show a greater degree of blockade in tissues
that are frequently depolarizing (for example, during tachycardia, when
the sodium channels open often).
This property is called use-dependence (or state-dependence) and it
enables these drugs to block cells that are discharging at an abnormally
high frequency, without interfering with the normal, low-frequency
beating of the heart.

15. Classification:
Class I anti arrhythmic drugs are classified into three sub classes:
Class IA
• Quinidine
• Procainamide
• Disopyramide
Class IB
• Lidocaine
• Mexiletine
• Tocainide
Class IC
• Flecanide
• Propafenone

17. CLASS IA
Blocking of the fast sodium channel interferes with rapid depolarization
and decreases conduction velocity.
This will increases the duration of the cardiac action potential.
These drugs decrease rate of rise of phase 0
Block Na channels preferentially in open state ,so decrease the no. of
available Na channels for membrane depolarization
Increase APD, and ERP

18. In addition to blocking the fast sodium channel (Phase 0) some class I
agents also block the potassium channel (Phase 3)
Potassium channel blockade directly affects the duration of the cardiac
action potential and the effective refractory period
All drugs have same effects but they differ in pharmacokinetics and
adverse effect.

20. QUINIDINE
Quinidine is d-isomer of quinine obtained from cinchona tree.
Quinidine binds with sodium channel and prevent sodium influx, thus
slowing the rapid upstroke during phase 0
It also decreases the slope of phase 4 depolarization and inhibits
potassium channels. Because of these action it decreases conduction
velocity and increases refractoriness
Additionally It has anti cholinergic activity (M receptor block) on SA
and AV NODE which increases HR and AV conduction.
Inc: PR,QRS,QT interval

21. Therapeutic uses:
Effective in the treatment of acute and chronic supraventricular
arrhythmias
Prevents recurrence of supraventricular tachyarrythmias or suppress
premature ventricular contractions and slow the ventricular rate in the
AF.
Supraventricular tachyarrthmias associated with Wolff-Parkinson-White
syndrome are effectively suppressed by quinidine.

22. Quinidine is most often administered orally in a dose of 200 to 400 mg
four times daily.
Oral absorption is rapid,with peak concentrations in the plasma
attained in 60 to 90 min. and elimination half-time of 5 to 12 hrs.
Intravenous route is rarely used due to vasodilation and myocardial
depression.

23. Adverse effects:
 nausea, vomiting, diarrhoea.
 large doses may produce cinchonism( tinnitus, ocular dysfunction,
CNS excitation). hypotension,
 prolongation of QRS and increase in QT interval associated with
syncope( which is due to ventricular arrhythmia induced by quinidine),
 Torsade de pointes.
 Thrombocytopenia that disappear on drug withdrawal.
 Enhances digoxin toxicity.

24. PROCAINAMIDE
It is a derivative of local anesthetic procaine.
Less M receptor blockade than quinidine, but more cardio depressant.
Orally effective, often substitution of quinidine.
Increase PR,QRS,QT interval
It Decreases re-entry by causing bidirectional block.

25. Indications:
 Effective in premature atrial contractions, PSVT, Atrial fibrillation.
 It converts atrial flutter or atrial fibrillation to sinus rhythm although it
has value in preventing reoccurrence of these arrhythmias once they
have been terminated by DC cardio version.
 Majority of patient of ventricular tachycardia respond to
procainamide.

26. Can be administered IV at a rate not exceeding 100mg every 5 min until
the rhythm is controlled(max. 15 mg/kg).
When cardiac arrthymia is controlled,a constant rate of infusion(2 to
6mg) is used to maintain therapeutic conc.
The therapeutic blood level is 4 to 8 mcg/ml.

27. Adverse effects:
 With chronic use, procainamide causes a high incidence of
side effects, including
 A reversible lupus erythematosus–like syndrome that
develops in 25 to 30 percent of patients..
Toxic concentrations of procainamide may cause asystole
or induction of ventricular arrhythmias.
Central nervous system (CNS) side effects include
depression, hallucination, and psychosis. With this drug,
gastrointestinal intolerance is less frequent than with
quinidine

28. DISOPYRAMIDE
It produces a negative ionotropic effect that is greater than the weak
effect exerted by quinidine and procainamide, and unlike the latter
drugs, disopyramide causes peripheral vasoconstriction.
The drug may produce a clinically important decrease in myocardial
contractility in patients with pre existing impairment of left ventricular
function
Disopyramide is used in the treatment of ventricular arrhythmias as an
alternative to procainamide or quinidine.
Dose : 100-300mg 6-8hrly
Adverse effects: it shows effects of anticholinergic activity (for example,
dry mouth, urinary retention, blurred vision, and constipation).

29. CLASS I(B) ANTIARRHYTHMIC
DRUGS

30. These drugs have minimal effect on rate of depolarization and
 They decrease APD and ERP. of purkinje fibers.
They block inactivated channels.
Examples are: Lidocaine, mexiletine, tocainide

31. LIDOCAINE
 Lidocaine (xylocaine, or lignocaine ) is a common local anesthetic
drug.
It is used intravenously for the treatment of ventricular
arrhythmias (for acute myocardial infarction, digoxin
poisoning, cardioversion or cardiac catheterization).
Effective in suppressing reentry cardiac arrhythmias,such as premature
ventricular contractions and ventricular tachycardia.
Lidocaine for IV administration differs from that used for local
anaesthesia.

32. Intramuscular absorption is nearly complete.
In emergency situation,lidocaine 4 to 5 mg/kg IM will produce therapeutic
plasma conc.
An initial administration of 2mg/kg IV followed by a continuous infusion of
1 to 4 mg per min would provide therapeutic plasma conc
Adverse effects:
Drowsiness
Confusion
Irritability
Convulsions.
Myocardial depression

33. TOCAINIDE (Tonocord)
Tocainide (Tonocard) is a class IB antiarrhythmic drug.
Mechanism of action:
It decreases His-purkinjie conduction.
Also it abolishes re-entry by causing bi-directional block.
Usual adult dose 400 to 800 mg administered every 8 hrs

34. Indications:
It is used in ventricular arrhythmia refractory to more conventional
therapy.
Adverse effects:
Light headedness
Dizziness
Nausea

35. MEXILETINE (Mexitil)
It is similar to lidocaine in action but it produces greater effect in
normal cardiac tissues than does lidocaine.
The addition of amine group enables mexiletine to avoid significant
hepatic first pass metabolism that limits the effectiveness of orally
administered lidocaine.
The usual adult dose is 150 to 200mg every 8 hrs orally..

36. Mechanism of action:
It slows conduction in the heart and makes the heart tissue less
sensitive.
Indications:
It is used to treat arrhythmias within the heart or seriously irregular
heart beats.

37. Adverse effects:
Dizziness
Heartburn
Nausea
Nervousness
Trembling
Unsteadiness
Widening of QRS wave
GI distress
Chest pain (rare)

38. CLASS I(C) ANTIARRHYTHMIC
DRUGS

39. Class IC antiarrhythmic medications are proarrhythmic, and their use
should be limited to patients without structural heart disease.
Class Ic does not significantly affect the action potential .It dec: QT
interval b/c these drugs have less effect on K rectifier current.
E.g. Moricizine, Flecainide, Propafenone

40. Potent blocker of Na & K channel with slow unblocking
kinetics.
Indication:
After digoxin it is 2nd line drug in the treatment of fetal
arrhythmia, many types of supraventricular tachycardias,
including AV nodal re-entrant tachycardia (AVNRT) and Wolff-
Parkinson-White syndrome(WPW). This is because of the
action of flecainide on the His-Purkinje system.
It is also used in ventricular tachyarrhythmias.
FLECAINIDE (TAMBOCOR):
Mechanism of
action:

41. Contraindications:
 Flecainide is contraindicated in patients with pre-existing
second- or third-degree AV block, or with right bundle branch
block when associated with a left hemiblock (bifascicular block),
unless a pacemaker is present to sustain the cardiac rhythm
should complete heart block occur.
Flecainide is also contraindicated in the presence of cardiogenic
shock or known hypersensitivity to the drug.

42. PROPAFENONE (Rythamol)
Mechanism of Action:
Slowing the influx of sodium ions into the cardiac muscle cells, causing
a decrease in excitability of the cell.
Indication:
Life-threatening ventricular arrhythmias,
atrial fibrillation (AF) or in patients exclusively with atrial flutter.
Contraindication:
hepatic or renal dysfunction
Asthma
CHF
Bradycardia.

43. Indication:
Life threatening ventricular arrhythmias (eg, sustained ventricular
tachycardia).
Used to treat irregular heartbeats (arrhythmias) and maintain a
normal heart rate.
Other II c drugs:
1. Moricizine works by inhibiting the rapid inward
sodium current across myocardial cell membranes.
2. Ethmozine shortens Phase II and III repolarization,
resulting in a decreased action potential duration
and effective refractory period.

44. Contraindications:
 Ethmozine® (moricizine hydrochloride) is contraindicated in patients
with pre-existing second- or third-degree AV block and in patients with
right bundle branch block when associated with left hemiblock
(bifascicular block) unless a pacemaker is present.
Ethmozine® is also contraindicated in the presence of cardiogenic
shock or known hypersensitivity to the drug.

45. CLASS II ANTIARRHYTHMIC
DRUGS

46. .

47. Mechanism of action :
The antiarrythmic effects most likely reflect blockade of the responses
of beta receptors.
As a result the rate of spontaneous phase 4 depolarisation and
sinoatrial node discharge is decreased.
Rate of conduction of cardiac impulses through the atrioventricular
node is slowed as reflected by a prolonged P-R interval on the ecg.

48. The usual oral dose of propranolol for chronic suppression of
ventricular arrhythmias is 10 to 80 mg every 6 to 8 hrs.
For emergency suppression of cardiac arrhythmias in an
adult,propranolol may be administered IV in a dose of 1mg per min(3-
6mg)
Onset of action – 2-5 min,
Duration of action -3-4hrs.
Administration at 1 minute intervals is intended to minimize the
likelihood of excessive pharmacological effects on the conduction of
cardiac impulses.

49. Propanolol and esmolol are effective for controlling the rate of
ventricular response in pts with atrial fibrillation and atrial flutter.
Esmolol IV loading dose 500mcg/kg over 1 min followed by
maintenance of 50mcg/kg/min is effective
Comparable doses of metaprolol 5-15 mg IV over 20min,which lasts 5-7
hrs produces antiarrhytmic effects similar to propranolol‘.
Acetabulol is effective in treatment of frequent premature ventricular
contractions.

50. Adverse effects:
Bradycardia
Hypotension
Myocardial depression
Bronchospasm
Fatigue
Insomnia

51. CLASS III ANTIARRHYTHMIC DRUGS

52. POTASSIUM CHANNEL BLOCKERs
Potassium-channel blockers comprise the Class III
antiarrhythmic compounds according to the Vaughan-
Williams classification scheme.
These drugs bind to and block the potassium channels that
are responsible for phase 3 repolarization.
Therefore, blocking these channels slows (delays)
repolarization, which leads to an increase in action potential
duration and an increase in the effective refractory period
(ERP).

53. On the electrocardiogram, this increases the Q-T
interval.
This is the common effect of all Class III
antiarrhythmic drugs.
The electrophysiological changes prolong the
period of time that the cell is unexcitable
(refractory) and therefore make the cell less
excitable.

54. By increasing the ERP, these drugs are
very useful in suppressing
tachyarrhythmia's caused by reentry
mechanisms.
Reentry occurs when an action
potential reemerges into normal tissue
when that tissue is no longer refractory.
 When this happens, a new action
potential is generated prematurely
(before normal activation) and a
circular, repeating pattern of early
activation can develop, which leads to a
tachycardia.
If the ERP of the normal tissue is
lengthened, then the reemerging action
potential may find the normal tissue
refractory and premature activation will
not occur.

55. CLASS III ANTIARYTHMIC DRUGS
BRETYLIUM
AMIODARONE
SOTALOL

56. BRETYLIUM
Bretylium blocks the release of noradrenaline from
nerve terminals.
 In effect, it decreases output from the peripheral
sympathetic nervous system.
It also acts by blocking K+channels and is considered a
class III antiarrhythmic
Is no longer recommended for treatment of ventricular
fibrillation during cardiopulmonary resuscitation nd
removed from ACLS support algorithm.

57. Amiodarone a benzofurane derivative used for various
types of cardiac dysrhythmias, both ventricular and
atrial.
Mechanism of action:
Amiodarone is categorized as a class III antiarrhythmic
agent, and prolongs phase 3 of the cardiac action
potential, the repolarization phase where there is
normally decreased calcium permeability and
increased potassium permeability.
It prolongs the effective refractory period in all cardiac
tissues.
AMIODARONE

58. Amiodarone shows beta blocker-like and potassium
channel blocker-like actions on the SA and AV nodes,
increases the refractory period via sodium- and
potassium-channel effects, and slows intra-cardiac
conduction of the cardiac action potential, via sodium-
channel effects

59. After initiation of oral therapy,a decrease in ventricular
tachyarrhythmias occurs within 72hrs.
Amiodarone oral dose 100-400 four times daily
Maintenance dose is decreased to 400mg daily for VT &
200mg daily for SVT.
Administered IV loading dose 15mg/min for 10
min,1mg/min for 6hrs followed by maintenance dose of
0.5-1mg/min.
Amiodarone 300 mg IV is recommended in presence of
ventricular tachycardia or fibrillation that is resistant to
electrical fibrillation.

60. Contraindications:
Individuals who are pregnant or may become pregnant are
strongly advised to not take amiodarone.
It is contraindicated in individuals with sinus nodal
bradycardia, atrioventricular block, and second or third
degree heart block who do not have an artificial pacemaker
Individuals with baseline depressed lung function should be
monitored closely if amiodarone therapy is to be initiated.

61. Adverse effects:
Most common side effects are:
Pulmonary alveolitis
Dizziness, lightheadedness, or fainting
Fever (slight)
numbness or tingling in the fingers or toes
painful breathing
trouble with walking

62. Less common side effects are:
Blue-gray coloring of the skin on the face, neck, and
arms
Blurred vision or blue-green halos seen around objects
Dry eyes
Fast or irregular heartbeat
Nervousness
Sensitivity of the eyes to light
Slow heartbeat
Sweating
Swelling of the feet or lower legs trouble with sleeping

63. SOTALOL
Sotalol is a drug used in individuals with rhythm
disturbances (cardiac arrhythmias) of the heart, and to
treat hypertension in some individuals.
It is a non-selective competitive β-adrenergic receptor
blocker that also exhibits Class III antiarrhythmic
properties by its inhibition of potassium channels.
Because of this dual action, Sotalol prolongs both the PR
interval and the QT interval.

64. Indicated in ventricular arrhythmias .
Daily oral dose is 240-320mg administered twice daily
The dosing intervals should be lengthened in pts with renal dysfunction
Most dangerous side effect of sotalol is torsades de pointes,reflecting
prolongation of the QTc interval on ECG.

65. CLASS IV ANTIARRHYTHMIC
DRUGS:

66. CLASS IV ANTIARRHYTHMIC DRUGS:
•Class IV drugs are calcium channel blockers.
•They decrease the inward current carried by
ca+2 resulting in a decreased rate of phase 4
spontaneous depolarization.
•Also slow conduction in tissues that depend
on calcium currents , such as av node.
•Major effect of ccbs is on vascular smooth
muscles & on heart.

67. VERAPAMIL:
•Verapamil is a prototype drug.
•Shows greater action on heart than on vascular smooth
muscle.
Cardiac effects:
 It usually slows the sinoatrial node by its direct
action.
 But its hypotensive action may occasionally result in
a small reflex increase of sinoatrial nodal rate.
 It can suppress both early & delayed after
depolarizations & may antagonize slow responses
arising in severly depolarized tissue. Verapamil
blocks both activated & inactivated L-type calcium
channels.

68. Extra-cardiac effects:
•Verapamil cause peripheral vasodilation ,which may
be beneficial in HTN & peripheral vasospastic
disorders.
•Its effects on smooth muscle produce a no. Of cardiac
effects.
•Supra ventricular tachycardia is the major arrhythmia
indication for verapamil.
•Usual dose is 5-10mg IV(75 to 150 mcg/kg) over 1 to 3
min followed by continuous infusion of abt 5mcg/kg/min.
•Chronic treatment with oral verapamil,80-120mg every
6-8hrs may be useful for prevention of PSVT.
Therapeutic uses:

69. Adverse effects:
•Also reduce ventricular rate in atrial fibrillation or
flutter.
•Occasionally useful in ventricular arrhythmia.
•Iv verapamil in a patient with sustained ventricular
tachycardia can cause hemodynamic collapse.
• Verapamil have –ve inotropic properties.
•May be contraindicated in patients with preexisting
depressed cardiac function.
• Verapamil can produce a decrease in BP b/c of
peripheral vasodilation –an effect that is actually
beneficial in treating HTN.

70. DILTIAZEM
It is a class III antianginal drug, and a class IV antiarrythmic.
Mechanism of action:
Diltiazem is a potent vasodilator, increasing blood flow and variably
decreasing the heart rate via strong depression of AV node conduction.
 Its pharmacological activity is somewhat similar to verapamil.
It is a potent vasodilator of coronary and peripheral vessels, which
reduces peripheral resistance and afterload.

71. Because of its negative inotropic effect, diltiazem causes a modest
decrease in heart muscle contractility and reduces myocardium oxygen
consumption.
 Its negative chronotropic effect results in a modest lowering of heart
rate, due to slowing of the sinoatrial node. It results in reduced
myocardium oxygen consumption.
Because of its negative dromotropic effect, conduction through the AV
(atrioventricular) node is slowed, which increases the time needed for
each beat. This results in reduced myocardium oxygen consumption.
Diltiazem,20mg IV,produces antiarrythmic effects similar to those of
diazepam.

72. OTHER DRUGS

73.  DIGOXIN
Mechanism of action:
 Digoxin shortens the refractory period in atrial & ventricular
myocardial cells while prolonging the ERF & diminishing conduction
velocity in the AV node.
It is used to control the ventricular response rate in atrial fibrillation &
flutter.
Miscellaneous :

74. Usual oral dose is 0.5 to 1.0mg in divided doses over 12 to 24hrs.
Digoxin toxicity:
At toxic conc. it causes ectopic ventricular beats that may result in
ventricular tachycardia & fibrillation.
[note: this arrhythmia is usually treated with Lidocaine].

75. Indications:
CHF
Atrial arrhythmia
Heart failure
Adverse effects:
 GI upset
 Yellow vision
 ECG will show increased PR interval
 ST scooping
 T-WAVE inversion

76. ADENOSINE
It is a naturally occurring nucleoside, but at high doses it decreases
conduction velocity, prolongs the refractory period, & decreases
automaticity in the AV node.
Used for acute treatment of PSVT,including that due to conduction
through accessory pathways in pts with WPW syndrome.
Usual dose is 6mg IV followed,if necessary,by a repeat injection 12mg IV
about 3 min later.
Toxicity:
 It has low toxicity, but causes flushing, chest pain, & hypotension.

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

78. To prevent intraop arrhythmias one must be careful with:
Adequate depth of anaesthesia
Analgesia
Hypercarbia
hypoxaemia etc.

79. Drugs of choices
S.
No
Arrhythmia Drug
1 Sinus tachycardia Propranolol
2 Atrial extrasystole Propranolol,
3 AF/Flutter Esmolol, verapamil ,digoxin
4 PSVT Adenosine ,esmolol
5 Ventricular Tachycardia Lignocaine , procainamide ,
Amiodarone
6 Ventricular fibrillation Lignocaine, amiodarone
7 A-V block Atropine , isoprenaline

80. THANK YOU! 