1) Arrhythmia is any deviation from the normal rhythm of the heart and can be caused by abnormalities in impulse generation or conduction. 2) There are several types of cardiac tissue with different electrophysiological properties, including pacemaker and contractile tissues. 3) Mechanisms of arrhythmia include enhanced automaticity, triggered activity, and reentry. 4) Antiarrhythmic drugs are classified based on their effects on ion channels and are used to treat various arrhythmias depending on their properties and side effect profiles.

1. Anti-arrhythmic drugs
Dr. Javed Akhtar
JR
KGMU

2. A-RHYTHM
Def- Arrhythmia is deviation of heart from normal RHYTHM
RHYTHM
1) HR- 60-100
2) Should origin from SA Node
3) Cardiac impulse should propagate through normal conduction
pathway with normal velocity

3. Source: Google Images

4. Types of cardiac tissue
AUTOMATIC/ PACEMAKER/ CONDUCTING FIBRES (Ca++ driven tissues)
• Includes SA node, AV node
• Capable of generating their own impulse
• Normally SA node acts as Pacemaker of heart
NON-AUTOMATIC MYOCARDIAL CONTRACTILE FIBRES (Na+ driven
tissues)
• Can not generate own impulse
• Includes atria and ventricles

5. Non-automatic Myocardial Contractile Fibres
Source: Google Images

6. AUTOMATIC/ PACEMAKER/ CONDUCTING FIBRES
Source: Google Images

7. Action potential in Pacemaker Cells Action potential in Myocardium
•Prepotential :
Slow Na⁺(funny channels)
Ca²⁺ influx (through T-type Ca²⁺
channels)
Decrease in K⁺ efflux
•Action potential :
Depolarization(phase 0): increase
in Ca²⁺ influx through L type Ca²⁺
channel
Repolarization(phase 3): increase
in K⁺ efflux
Phase Name Cause
0 Initial rapid
depolarization
and overshoot
Opening of Na⁺
Channels
1 Initial rapid
repolarization
Efflux of K⁺
Closure of Na⁺
channels
2 Plateau Ca²⁺ influx (L
type)
and K⁺ efflux .
3 Repolarization Closure of Ca²⁺
channels
K⁺ efflux through
various type of K⁺
channels
4 Resting
membrane
potential

8. Mechanism of Arrhythmia

9. 1. Abnormal impulse generation:
• Enhanced automaticity
2. Triggered activity (after depolarization):
• Early after depolarization
• Delayed after depolarization
3. Re-entry phenomenon

10. Enhanced Automaticity
• Cell other than SA node take control as pacemaker
• Results due to pathological increase in phase 4 slope -
accelerated pacemaker rate
• May result from current of Injury
• Ischemia, high sympathetic tone, electrolyte imbalance
• Example: ectopic atrial tachycardia, ventricle tachycardia
following MI

11. Triggered Activity (After Depolarization)
• A normal AP interrupted/followed by
a abnormal depolarization
• Delayed After Depolarization: – due
to Ca++ overload
• After attaining RMP
• Caused by Digoxin toxicity,
Myocardial Ischaemia or Adrenergic
stress or Heart failure
Source: Goodman Gilman 13th edition

12. Early Afterdepolarization
• Interrupting phase 3 repolarization
• Multiple ion channels and transporters can
contribute to EADs
• Membrane potential oscillates
• Frequently associated with long Q-T
interval
Source: Goodman Gilman 13th edition

13. Reentry
• Primarily due to abnormality of conduction
• Impulse may recirculate in the heart
• Repetitive activation without the need for any new impulse
Circus movement reentry (anatomically defined circuit): WPW
syndrome, PSVT
• Permanently cured by radiofrequency catheter ablation

14. Reentry
Functional reentry: ischemia, differences in refractoriness
• Polymorphic ventricular tachycardia
• Atrial/ventricular fibrillation

15. Source: Google Images

16. Important Types of Cardiac Arrhythmias

17. • Extrasystole: premature beats due to abnormal
automaticity/after depolarization
• Paroxysmal Supraventricular Tachycardia (PSVT): Sudden
onset of atrial tachycardia 150-200/minute (1:1), reentry
phenomenon (AV node)
• Atrial Flutter: 200-350/minute (2:1 to 4:1 AV block), reentrant
circuit in right atrium

18. • Atrial Fibrillation: Asynchronous activation of atrial fibers 350-
550/min with irregular 100 to 160 ventricular beats
• Ventricular tachycardia: 4 or more consecutive extrasystole of
ventricles – monomorphic or polymorphic
• Ventricular Fibrillation: rapid irregular contractions – fatal (MI,
electrocution)

19. • Torsades de pointes: polymorphic ventricular tachycardia,
rapid asynchronous complexes, fatal
• A-V Block: vagal influence or ischemia - 1st, 2nd and 3rd
degree – slowed conduction, drop beat and number

20. Source: Goodman Gilman 13th edition

21. Treatment of Arrhythmia

22. Vaugham-Williams classification
K+
Na+
β receptor
Ca++
Class I – Na+ Channel Blockers
Class II – β Blockers
Class III – K+ channel blockers
Class IV – Ca++ channel blockers
Class V – Miscellaneous
Sarcoplasmic reticulum

23. Supraventricular Tachycardia
Aim: prevent propagation to
ventricle
1. Blocking AV node
i. CCB: as depolarization occur
due to calcium
ii. Block sympathetic system
iii. Adenosine
iv. Parasympathomimetic drug:
digoxin
2. Control rhythm
i. Na+ blocker
ii. K+ blocker

24. Treatment of SVT/PSVT
1. Acute attack: short acting drug
• DOC: adenosine(I.V)
1. Prophylaxis: long acting AV node blocking drugs
• β blocker: decrease sympathetic system
• CCB: verapamil/diltiazem
• Digoxin (parasympathomimetic activity)

25. Atrial fibrillation/flutter
1. Acute attack:
• TOC: Cardioversion
• DOC: Ibutelide
2. Long term
1. Rate control
• Block AV node
• DOC: β blocker
2. Rhythm control
• Na+ channel blocker
• K+ channel blocker
Source: Google Images

26. Ventricular tachycardia/ fibrillation
Aim : suppress myocardial tissue
i. Na+ channel blocker (lignocaine)
ii. K+ channel blocker (amiodarone)
iii. β blocker (propranolol)
Source: Google Images

27. Classification And Drugs

28. Classification
Class Actions Drugs
I Membrane stabilizing agents
(Na+ channel blockers)
A. Moderately decrease dv/dt of 0 phase Quinidine, Procainamide
B. Little decrease in dv/dt of 0 phase Lidocaine, Mexiletine
C. Marked decrease in dv/dt of 0 phase Propafenone, Flecainide
II Antiadrenergic agents (β blockers) Propranolol, Esmolol
III Agents widening AP (prolong repolarization and
ERP)
Amiodarone, Dronedarone,
Dofetilide, Ibutilide, Sotalol
IV Calcium channel blockers Verapamil, Diltiazem

29. Class 1a Class 1b Class 1c
Na+ channel Block Block Block
Duration of block 1-10 sec < 1 sec >10 sec
State of Na+
channel
Open Inactivated Open
K+ channel Blocker Opener Blocker (negligible
effect)
Effect on QT
interval
Increased Decreased No effect
Additional property AV Node blocker
Anticholinergic
effects
AV Node blocker

30. Class I Effect On Action Potiential

31. • Block Na+ channel in open state
• Moderately delay channel recovery
• Suppress A-V conduction
• Prolong refractoriness (normal as well as accessory pathways)
• K+ channel blocker (QT prolongation )
• Anticholinergic effects
• α blocking property
SUBCLASS I A

32. Quinidine
Therapeutic Uses:
 Atrial flutter & fibrillation
 Ventricular tachycardia & fibrillation
Drug Interaction:
 Increases digoxin plasma levels
 Risk of torsades de pointes is increased with diuretics
 Synergistic cardiac depression with β –blockers, Verapamil

33. Toxicity:
• Cinchonism (dizziness, tinnitus, vertigo)
• Diarrhea
• Arrhythmia or asystole (torsade de pointes)
• Anticholinergic actions → inhibit vagal effects
• Depress contractility
• ↓ BP(α-blocking)
• Rare: rashes, fever, hepatitis, thrombocytopenia, etc

34. • Derivative of procaine
• No anticholinergic action
• No α-blocking action unlike quinidine
• Action similar to quinidine
Adverse effects:
• SLE
• Higher doses can cause hypotension (due to ganglion block)
• Heart block and QT prolongation
Procainamide

35. • Block Na+ channel in open state
• Most potent sodium channel blocking effects
• Marked delay channel recovery
• Markedly block A-V conduction
• Prolong refractoriness (normal as well as accessory pathways)
• Negligible effect on K+ channels
SUBCLASS I C

36. • Maximum proarrhythmic property
• Drugs: Flecainide, Propafenone
Used: only for refractory and life threating condition
• Atrial flutter & fibrillation
• Ventricular tachycardia & fibrillation
• Flecainide: DOC for acute therapy of WPW syndrome
SUBCLASS I C

37. • Block Na+ channels
• More in the inactivated than in the open state
• Do not delay channel recovery (channel recovery time < 1S)
• K+ channel opener (↓ QT)
• No effect on AV node
• Lidocaine (Lignocaine) and Mexiletine
• Mexiletine is an orally active lignocaine derivative with all the
properties of lignocaine
SUBCLASS IB

38. • Most prominent action is suppression of automaticity in ectopic foci
• Useful in acute ischemic ventricular arrhythmias
• Depolarized/damaged fibers are significantly depressed
• Lidocaine is inactive orally
• High first pass metabolism (so loading dose given)
• Main toxicity is dose related neurological effects
lignocaine

39. Dose and preparation
• Lidocaine is given only by i.v. route
• 50–100 mg bolus followed by 20–40 mg every 10– 20 min or 1–3
mg/min infusion
• XYLOCARD, GESICARD 20 mg/ml inj

40. • Local anaesthetic
• Inactive orally
• Given IV for antiarrhythmic action
• Na+ channel blockade which occurs
• Only in inactive state of Na+ channels
• CNS side effects in high doses
• Action lasts only for 15 min
• Inhibits purkinje fibres and ventricles but
• No action on AVN and SAN
• Effective in Ventricular arrhythmias only

41. CLASS II
• Suppress adrenergic mediated ectopic activity
• Impedes A-V conduction
• Increase PR interval
• Prolong AV refractoriness
• Marked decrease in the slope of phase-4 depolarization
• Decrease automaticity occurs in SA node
• Propranolol, Esmolol, Metoprolol

42. Uses
• Idiopathic ventricular tachycardia
• Ventricular premature beats
• Congenital long QT syndrome(long term management)
• Cathecholamine induce arrhythmia
• Pheochromocytoma
• Exercise
• Emotional
• Rate control in atrial flutter and atrial fibrillation
• Termination of acute attack PSVT: Esmolol IV

43. Dose
Propranolol
• For rapid action, propranolol may be injected i.v. 1 mg/min
(max. 5 mg) under close monitoring
• Maintenance dose is 40–80 mg 2–4 times a day
Esmolol (for acute attack only)
0.5 mg/kg in 1 min followed by 0.05–0.2 mg/kg/min i.v. infusion

44. Class III drugs
• K+ channel blocker
• Delay in repolarization
• ERP increases
• Increase QT interval
• Causes torsade de pointes
• Maximum: ibutilide
• Minimum: amiodarone
• No effect: vernakalant
Source: Katzung & trevors 11th edition

45. • Amiodarone
• Dronedarone
• Ibutilide
• Dofetilide
• Sotalol
• Vernakalant

46. Amiodarone
• Widest spectrum anti arrhythmic drug
• Block: K+, Na+, Ca++, alpha and β receptor
• Least risk of QT prolongation
• High volume of distribution(loading dose given)
• Long duration of action: t1/2: 3-8 weeks
• Uses: VT, VF, AF, Atrial flutter

47. Dose
• Amiodarone is mainly used orally 400–600 mg/day for few
weeks, followed by 100–200 mg OD for maintenance therapy
• 100–300 mg (5 mg/kg) slow i.v. injection over 30–60 min
• Preparation: CORDARONE, ALDARONE, EURYTHMIC 100, 200
mg tabs, 150 mg/3 ml inj.

48. Side effects of amiodarone:
• Dose-related and increase with duration of therapy
• Pulmonary fibrosis
• Goitre, hypothyroidism and rarely hyperthyroidism
• Fall in BP, bradycardia
• Myocardial depression
• Liver damage
• Photosensitivity
• Corneal microdeposits

49. Dronedarone
• Noniodinated congener of amiodarone
• Less toxic
• Also less effective
• Used only as a substitute to amiodarone
• T1/2= around 24 hours
• Food increases absorption

50. Sotalol
• Nonselective β blocker having prominent Class III action
• It is a racemic mixture; the d-isomer has pure class III property,
while the I-isomer is a β blocker
• Used:
• Polymorphic VT
• WPW arrhythmias
• Maintaining sinus rhythm in AF/AFI

51. Ibutilide
• Structural analog of sotalol (but no β blocking property)
• Shortest acting K+ blocker
• Used for acute treatment of atrial fibrillation or atrial flutter
• I.V. route
• Only antiarrhythmic agent currently approved by FDA for acute
conversion of atrial fibrillation to sinus rhythm
• Other drugs used in atrial fibrillation are for controlling ventricular
rate

52. Dofetilide
• Pure class III antiarrhythmic
• A potential K+ channel blocker
• Uses: Atrial flutter & fibrillation
Vernakalant
• Multiple ion channel (Na+, K+, Ca++ blocker)
• Does not cause QT prolongation
• Use: Atrial fibrillation

53. Class IV drugs
• Calcium channel blocker
• Major effect on nodal tissue
• Verapamil and diltiazem is used
• No reflex tachycardia(as in Dihydropyridines)
• Cause AV nodal delay
• Suppresses automaticity and re-entry dependent on slow
channel response
• Suppress both early & delayed afterdepolarizations

54. • Effects in a calcium-dependent
cardiac cell in the AV node
• Reduce inward calcium current
during the AP and during phase 4
• Conduction velocity is slowed in
the AV node
• Refractoriness is prolonged
Source: Katzung & trevors 11th edition

55. Uses:
• Terminate PSVT
• Acute attack: verapamil 5 mg i.v. over 2–3 min is effective
• For preventing recurrences of PSVT, verapamil 60 to 120 mg
TDS may be given orally
• Control ventricular rate in atrial flutter or fibrillation

56. Adenosine
Receptor
• A1R(Gi Type) present on
 AV Node: block
 Bronchus: bronchoconstriction
• A2R (GS Type)
 Blood vessel: vasodilation
• M.O.A: stimulate adenosine receptor

57. Route: IV rapid infusion/ close to heart(jugular vein)
• Rapidly taken by cellular adenosine uptake protein
• Shortest action
Side effect:
• Vasodilation: flushing
• Bronchoconstriction: dyspnea
• So contraindicated in asthma and COPD

58. Drug interaction
1. Theophylline cause failure (adenosine receptor antagonist)
2. Dipyramidole causes toxicity (blocking cellular uptake)
Uses
• PSVT: Administered by rapid i.v. injection (over 1–3 sec) either as
the free base (6–12 mg) or as ATP (10–20 mg)
• Diagnosis of tachycardias dependent on A-V node

59. Magnesium
Mechanism of action is unknown but calcium channel blocking
property is possible mechanism
Use
• Acute treatment of long QT syndrome(both congenital and
acquired)
• As Calcium channel block trigger K+ opening which cause
repolarization

60. Atropine
• Stimulate heart
• SA node: increase heart rate
• AV node: increase conduction
Uses
• Sinus arrest
• Sinus bradycardia
• Inferior wall MI (vagal irritation Parasympathetic activity)
• AV nodal block reversal (digoxin toxicity)

61. Digoxin
• M.O.A: parasympathomimetic activity
• Block AV node
• Slow onset of action(not for acute condition)
Use
• Controlling ventricular rate in atrial flutter and atrial fibrillation

62. THANK YOU