Pharmacotherapy of Cardiac arrhythmias

1. Pharmacotherapy of Cardiac
Arrhythmia
Presenter – Dr. Sneha Dange, JR3
Dept. of Pharmacology,
GMC, Nagpur

2. Overview
 Electrophysiology of heart
 Cardiac arrhythmias
 Classification of antiarrhythmic drugs
 Miscellaneous antiarrhythmic drugs
 Drugs for bradyarrhythmias
 Recent advances
 Summary

3. Normal Conduction Pathway
SA node
Generates action
potential
AV node
Delivers the impulse to
bundle of His
Bundle of His
Purkinje fibres

4. -100
-80
-60
-40
-20
0
20
Phase 0
Phase 1
Phase 2
Phase 3
Phase 4
Na+
ca++
ATPase
mv Cardiac Action
Potential (non nodal
tissue)
Resting
membrane
Potential
Na+
m
Na+
Na+
Na+
Na+
Na+
h
K+
ca++
K+
K+
K+
ca++
ca++
(Plateau Phase)
K+
K+
K+ Na+
K+
Depolarization
30

5. Action Potential In Cardiac Nodal Tissues
 Resting membrane potential - 60 mV
 Excitation threshold potential - 40 mV
 Phase 0, 1, 2 & 3 are indistinguishable
 Conduction velocity is slower and ERP is longer
 Ca+2 influx (not Na+) dominates the upstroke (Depolarization)
 Steeper the diastolic depolarization (phase IV) – higher is the pacemaker rate
 SA Node has steepest and fastest phase IV over-rides other pacemaker tissue
 Outward K+ current in phase IV is smaller in all pacemaker tissues- RMP is less
– ve (-60mV)

6. -60
-40
-20
0
20
Phase 0
Phase 1
Phase 2
Phase 3
Phase 4
mv
Cardiac Action Potential (nodal tissue)
Resting
membrane
Potential
(Plateau Phase)
Depolarization
30

7. Effective Refractory Period (ERP)
 Absolute refractory period (ARP):
Phase 0 – mid-Phase III
Cell does not respond to any stimulus
 Relative refractory period (RRP):
Mid-Phase III – end of phase III
Cell can respond to a strong stimulus
 ARP + RRP = ERP
Depicts minimum interval between 2 propagated
responses

8. CARDIAC ARRHYTHMIA
Deviations from normal pattern of cardiac rhythm, due to
 Abnormalities in impulse formation (site/rate/rhythm)
 Abnormalities in impulse conduction
MI
Hypoxia
Acidosis / alkalosis
Electrolyte abnormalities
Excessive catecholamine exposure
Autonomic influences
Drug toxicities

9. MECHANISMS OF ARRHYTHMOGENESIS
1- Abnormal Impulse formation
Automaticity
Enhanced
Sinus
tachycardia
Depressed
Bradycardia
Ectopic focus
AP arises from sites
other than SA node
Triggered
activity
Delayed after
depolarization
Early after
depolarization
Torsades de
pointes

10. 2-Abnormal conduction
Conduction block
Complete
Idio-ventricular
rhythm
Incomplete
Dropped beats
Re-entry
Circus
movement
Accessory
tract pathways
Mechanisms Of Arrhythmogenesis
Premature beat,
paroxysmal
supraventricular
tachycardia (PSVT),
atrial flutter (AFL) &
ventricular fibrillation
(VF)

11. Mechanisms Of Arrhythmogenesis 2-Abnormal conduction

12. Bundle of Kent
•Present only in small populations
• Lead to re-excitation  Wolf-
Parkinson-White Syndrome (WPW)
Mechanisms Of Arrhythmogenesis
Accessory Tract Pathway
2-Abnormal conduction

13. ARRHYTHMIA
HEART RATE
(BPM)
OTHER CHARACTERISTIC FEATURES
Extrasystoles (ES): atrial,
nodal and ventricular
Due to abnormal automaticity/ after depolarization (AES,
VED, nodal ES)
QRS complex in VES is wide
PSVT 150 – 200
•Sudden onset atrial tachycardia with 1:1 AV conduction
•Seen in Re-entry / WPW syndrome
Atrial flutter (AFl)
350 – 550 •2:1 / 4:1 / higher AV block
• re-entry circuit in RA (main) / atrial ectopic foci
Atrial fibrillation (AF) Irregularly irregular
•Grossly irregular and often fast ventricular rate (~100-
160/min)
•Atria remain dilated (asynchronous atrial stimulation)
Ventricular tachycardia
(VT)
100 – 200
•Widened QRS complex
•≥ 4 consecutive ventricular extrasystoles
•Sustained / non-sustained
•Ectopic foci/after depolarizations/ re-entry
Ventricular fibrillation
•Irregular, rapid, fractionated activation of ventricles –
uncoordinated contractions
•Thus loss of pumping function
•Fatal unless reverted within 2-5 mins
•Most common cause of sudden cardiac death

14. Management of Arrhythmia
Pharmacological therapy (Anti-arrhythmic drugs)
Cardioversion
Pacemaker therapy
Surgical therapy e.g. aneurysmal excision
Interventional therapy – cathetor ablation

15. Classification of antiarrhythmic drugs
CLAS
S
MECHANISM ACTION NOTES
I
Na+ channel
blocker
Change the slope of phase 0
(reduce the rate of depolarisation)
Can abolish
tachyarrhythmia
caused by reentry
circuit
II β blocker
↓heart rate and conduction
velocity
III
K+ channel
blocker
• ↑action potential duration
(APD) & ↑ Effective Refractory
Period (ERP).
• Delay repolarization.
Inhibit reentry
tachycardia
IV
Ca+2 channel
blocker
Slowing the rate of rise in phase
IV AP of SA node
↓conduction velocity
in SA and AV node

16. Phase 0
Phase 1
Phase 2
Phase 3
Phase 4
R.M.P
(Plateau Phase)
Class I:
Na + channel blockers.
- Pacemaker potential
-
-
-
Class III:
K + channel blockers
-
Class IV:
Ca ++ channel blockers
Class II:
Beta blockers
Classification of Anti-Arrhythmic
Drugs

17. Vaughan Williams classification :
Classification of antiarrhythmic drugs
Class I
(Na+ channel blockers)
Membrane stabilizing agents
Class I A
Quinidine
Procainamide
Disopyramide
Class I B
Lidocaine
Mexiletine
Tocainide
Phenytoin
Class I C
Propafenone
Flecainide
Moricizine
Class II
(β blockers)
Antiadrenergic
agents
Metoprolol
Esmolol
Propranolol
Class III
(K+ Channel
blockers)
Widening action
potential
Amiodarone
Dofetilide
Ibutilide
Dronedarone
Sotalol
Class IV
(CCBs)
Verapamil
Diltiazem
Miscellaneous agents
Adenosine
Digoxin
Magnesium
Potassium

19. Class I (Na+ channel blockers)
Block Na+ channels  Reduce the rate of phase 0 depolarization
 Suppress automaticity
 Inhibitory activity shows ‘use dependence’
 More the frequency of Na+ channel activation, more is the block by these drugs
 prolong the ERP
Property of use dependence - block only high frequency Na+ channels in
myocardium

20. Class IA
Mechanism of action :
 Suppress ectopic pacemaker & abolish re-entry by
converting unidirectional block into bidirectional block
Blocks activated Na+ channels > inactivated
channel & slow rate of dissociation
(recovery time 1-10 sec)

21. Quinidine
 Has anti-vagal action
 Depresses myocardial contractility
 ECG - ↑ PR & QT interval & broaden QRS complex
 Side effect –
 Rise in blood levels & toxicity of digoxin
 Dose – 200-400 mg TDS orally
Class IA
Diarrhoea (MC)
Quinidine syncope
Cinchonism

22. Procainamide
 Cardiac electrophysiological action is almost identical to that of quinidine
 Differences are:
 Long term high dose therapy – SLE
Class IA
•Less effective in suppressing ectopic automaticity
•Less marked depression of contractility & AV conduction
•No anti-vagal action
•No α blocking activity
•Doesn’t alter plasma levels of digoxin

23. Procainamide
Class IA
Abolition of arrhythmia:
500 mg iv loading dose (25 mg/min inj.) f/b 2 mg/kg/hr
Or
500 mg oral / im f/b 250-500 mg every 2 hrs
Maintenance dose:
500 mg every 4-6 hrs
To terminate VT & some supraventricular arrhythmia
WPW & to prevent recurrence of VF

24. Disopyramide
 Prominent cardiac depressant & anti-cholinergic action
 No α-blocking activity, ↑ PR & broaden QRS complex less marked
 No interaction with digoxin
 Longer T1/2 (6-8 hrs)
 Side effects – anti-cholinergic are most prominent
 Dose – 100-150 mg 6-8 hrly oral
 Uses – 2nd line drug for prevention of recurrence of ventricular arrhythmia
 Contraindication- sick sinus, cardiac failure, prostate hypertrophy
Class IA

25.  Mechanism of action :
 Like quinidine, also abolish ventricular re-entry tachycardia
Class IB
• Block inactivated > activated Na+ channels
• Do not delay channel recovery (recovery time < 1 sec)

26.  Most prominent action –
 Inactive orally due to high first pass metabolism
 Action of IV bolus lasts only 10-20 mins due to redistribution
Class IB
I. Suppression of automaticity in ectopic foci but not of SA node
II. Rate of Phase 0 depolarization & conduction velocity in AV bundle, ventricles
is not decreased
III. ↓ APD in Purkinje Fibres (PF) & ventricular muscles, no effect on atrial fibres
IV. Suppresses re-entrant ventricular arrhythmia either by abolishing 1 way block
or producing 2 way block
Lidocaine

27.  T1/2:
Early distribution phase – 8 mins
Later elimination phase – 2 hrs
 Dose: 50-100 mg iv bolus f/b 20-40 mg every 10-20 min (Max
300 mg in 1 hr) f/b maintenance dose 1-3 mg/min infusion
 Side effects: Dose related neurological effects
 No proarrhythmic potential & least cardiotoxic
 Uses: termination of VT, Prevention of Ventricular arrhythmia
after cardioversion in MI , Digitalis induced arrhythmia
Class IB
Lidocaine

28.  Local anaesthetic & orally active
 Tremors – early sign of toxicity, Bradycardia, hypotension & accentuation of
AV block – iv
 T1/2 – 9-12 hrs
 Dose: 100-250 mg iv over 10 mins, 1mg/min infusion, Oral 150-200 mg TDS
with meals
 Use: Post MI ventricular arrhythmia as alternative to lidocaine
Class IB
Mexiletine
 Automaticity in PF is ↓ by both ↓ phase 4 & ↑ threshold voltage
 By ↓ rate of 0 phase depolarisation in ischemic PF, converts 1 way block
into 2 way block

29.  Blood dyscrasias, pulmonary fibrosis, agranulocytosis, thrombocytopenia,
nausea, paresthesia, tremors
Class IB
Tocainide
 Doesn’t aggravate AV block
 Doesn’t produce hypotension
 Use : Terminate digitalis induced arrhythmia
Phenytoin

30.  Mechanism of action:
 High proarrhythmic potential when administered chronically
 Markedly ↓ rate of phase 0 depolarisation in Purkinje & ventricular
myocardial fibres
 ↓ automaticity, ↓ AV conduction & contractility
 Retard re-entry of retrograde & anterograde impulses
 Prominent depressant action on normal heart as well
Class IC
Most potent Na+ channel blocker with more prominent
action on open state & longest recovery time (> 10 sec)

31.  Prototype drug which markedly delays Na+ channel recovery
 No consistent effect on APD & no β blocking activity
 CAST study, ↑ mortality in patients recovering from MI
 Highest proarrhythmic potential
 Reserved for resistant cases of paroxysmal AF & for life-threatening
sustained VT in patients not having CHF
 T1/2 is 20 hours Dose- 100-200 mg twice daily
Class IC
Flecainide

32.  By blocking Na+ channels, depresses impulse transmission & has profound
effect on His-Purkinje as well as accessory pathway conduction
 Anterograde & retrograde conduction in WPW syndrome is retarded
 Prolongs APD & has β blocking property – can precipitate CHF &
bronchospasm
 Bioavailability & T1/2 differ considerably among individuals
Class IC
Propafenone

33.  Side effects:
Proarrhythmic
 Dose: 150 mg BD – 300 mg TDS
 Use: Prophylaxis & treatment of PSVT involving AV node / accessory
pathway & to maintain sinus rhythm in AF
 allows 1:1 AV transmission by slowing atrial rate in AF
Class IC
Propafenone

34.  Potent Na+ channel blocker
 Has properties of class IA, IB and IC antiarrhythmics
 Use: limited to life-threatening ventricular arrhythmias
 Advantage: Lower incidence of proarrhythmogenic effects
 Dose: 200-400mg TDS, oral
 Adverse effect: GI distress, dizziness
Class IC
Moricizine

35. Class II Drugs (β blockers)
Mechanism of action
Slows sinus & AV nodal conduction which result in ↓ in HR & prolongation in
PR interval
QT & QRS complex are not altered significantly
β blockers that competitively block catecholamine induced
stimulation of cardiac β receptors & depress phase 4
depolarisation of pacemaker cells

36.  Marked ↓ in slope of phase 4 depolarization & automaticity in SA node, PF
& other ectopic foci when same has ↑ due to adrenergic influence
 Prolong ERP of AV node
 ECG: Prolonged PR interval
 Dose: Rapid action: Slow iv infusion 1-3 mg/min in 50 ml of 5% glucose
solution (max 5 mg) Oral: 40-80 mg
Class II
Propranolol
 Inappropriate sinus tachycardia
 AES / VES, especially provoked by emotion or exercise
 Prevent recurrences of PSVT (less effective than Adenosine & Verapamil )
 Control VT in AF/AFI
 Terminate torsades de pointes

37.  Quick & short acting β1 blocker administered IV for emergency control of
ventricular rate in AF / AFL
 Terminate supraventricular tachycardia
 Mainly used for arrhythmias seen in pheochromocytoma & anesthesia
where rapid b-blockade is required
 Dose: Loading dose of 0.5 mg/kg in 1 min followed by 0.05–0.2 mg/kg/min
i.v. infusion
Class II
Esmolol

38. Class III Drugs (K+ Channel blockers))
Mechanism of action:
Prolong ERP
QT & PR interval are prolonged
Tissue remains refractory even after full repolarization
Re-entrant arrhythmias are terminated
Prolongation of repolarisation by blocking outward
K+ channel during phase 3 of AP

39.  Iodine containing, highly lipophilic, long acting
 Conduction is slowed & ectopic automaticity is markedly depressed, but that
of SA node is only slightly affected
 Despite prolongation of APD, arrhythmia provoking potential of amiodarone
is low
Class III
Amiodarone
 Blocks Na+ channels
 Block delayed rectifier K+
channel
 Mild β blocking activity
 Ca2+ blocking action

40.  Incompletely & slowly absorbed from GIT
On daily oral ingestion, action develops over several days
On IV injection, action develops rapidly
 Volume of distribution is large & t1/2 – 3-8 weeks
 Side effects:
 Pulmonary alveolitis & fibrosis – most serious
 Hypotension, bradycardia & myocardial depression
– on IV injection & after drug accumulation
 Corneal microdeposits
 Photosensitization & sun burn like pigmentation
 Interferes with thyroid function
Class III
Amiodarone

41.  Orally 400–600 mg/day for few weeks, followed by 100–200 mg OD for
maintenance therapy
 Loading dose – 150 mg IV rapid infusion over 10min f/b slow infusion of 1
mg/min for 6 hrs then maintenance infusion of 0.5 mg/min for 24 hrs
 Uses –
 Resistant VT & recurrent VF
 Maintain sinus rhythm in AF
 Rapid termination of VT & VF and supraventricular arrhythmia – IV injection
 WPW tachyarrhythmia is terminated by suppression of both normal &
aberrant pathway
Class III
Amiodarone

42. Dronedarone
 Amiodarone like drug without iodine atoms
 Shorter t1/2 – 1-2 days
 More b-blocking action, increases myocardial APD,ERP & slows AV
conduction
 Dose: 400 mg BD orally
 Contraindicated – mod-severe CHF, 2nd 3rd Block, permanent AF
 Use: Prevent recurrence in patients with persistent AF
Class III

43. Ibutilide
Dofetilide
 Block rapid inward rectifier K+
channel
 Conversion of AF and AFl to
normal sinus rhythm
 Efficacy is higher in recent onset
cases & in AFI than AF
 T1/2 is 6 hours
Class III
 Pure Class III drug
 Prolongs APD & ERP by selectively
blocking rapid components of
delayed rectifier K+ current
 Converts AF / AFL to sinus rhythm in
~30% but more effective in
maintaining sinus rhythm in
converted patients
 Dose: 0.5 mg BD orally

44.  Prominent class III action of prolonging repolarisation by blocking cardiac
inward rectifier K+ channel
 Non-selective β blocker & effect is exhibited at doses below than that
required for prolongation of APD
 Limitation: Prolongation of APD & QT, risk of dose dependent torsade de
pointes
 Dose: 80 mg BD orally
 Used in polymorphic VT, maintainance of sinus rhythm in AF/AFL
Class III
Sotalol

45. Class IV Drugs (Ca2+Channel blockers))
Blocks both activated & inactivated L-type Ca2+ channels in myocardium
↓ in rate of depolarisation (phase 4) in SA & AV node & slowed
conduction through AV node
↑ in PR interval & ERP
Mechanism of action:

46.  Most prominent cardiac electrophysiological action
 Depress Ca2+ mediated depolarization
 This suppresses automaticity and re-entry dependent on slow channel
response
 Most consistent action - prolongation of A-V nodal ERP results in AV node
conduction is markedly slowed & re-entry through AV node is terminated
Class IV
Verapamil
Uses:
1 PSVT –
Terminate attack:- 5 mg IV over 2-3 min
Prevent recurrence:- 60-120 mg TDS orally
2. To control ventricular rate in AF or AFL:
First line drug - Dose dependent (40–120 mg TDS oral) reduction in ventricular rate
in AF & Afl
Injected i.v. for emergency control of ventricular rate in AF and AFL (5-10 mg/hr IV
infusion)
3. Re-entrant supraventricular and nodal arrhythmias are susceptible to
verapamil, but it is contraindicated in broad QRS complex WPW tachycardia

47.  Alternative to verapamil – termination & prophylaxis of PSVT
 For rapid control of ventricular rate in AF or AFI -
i.v. diltiazem is preferred over verapamil, because
 Dose: 5-15 mg/hour continuous infusion till adequate response
Class IV
Diltiazem
1. More easily titrated to the target heart rate
2. Causes less hypotension or myocardial depression
3. Used even in the presence of mild-to-moderate CHF

48. Miscellaneous agents
Stimulates adenosine receptors (A1)
Opens G-protein coupled K+ channel & inhibits SA
nodal, atrial & AV nodal conduction
Terminates re-entrant circuit through AV node & restores normal sinus rhythm in
PSVT
Administered by rapid i.v. injection (over 1–3 sec) free base 6–12 mg
or ATP(10-20mg)
terminates within 30 sec. >90% episodes of PSVT
Adenosine

49. Miscellaneous agents
Very short t½ in blood (~10 sec)
Advantages of adenosine for termination of PSVT are:
 Efficacy equivalent to or better than verapamil.
 Action lasts < 1 min, adverse effects are transient.
 No hemodynamic deterioration- can be given to patients with hypotension,
CHF or on β blockers
 Safe in wide QRS tachycardia
Side effects: Facial flushing, shortness of breath, bronchospasm, nausea,
metallic taste
Adenosine

50.  Mode of action:
 Na-K ATPase inhibition
 Positive inotrope
 Vagomimetic
 Uses: Supraventricular Tachycardia
 Digoxin Toxicity:
 Proarrhythmic
 Causes nausea/vomiting, lethargy, visual changes
Digoxin
Miscellaneous agents

51. Magnesium Potassium
Both / of K+ potentially
arrhythmogenic
Normal K+ :
impulse conduction velocity
automaticity in purkinje fibres
refractory period
Hypokalemia :
EAD
DAD
Ectopics
Hyperkalemia : Supress AV node & slows
conduction
 As MgSO4 – effective in terminating
refractory ventricular tachyarrhythmias,
in torsades de pointes
 In the past, to treat digitalis induced
arrhythmias in hypomagnesemic
patients
 MOA: blocking of Na+-K+ATPase, Na+
channels, K+ channels, Ca+2 channels
 Dose: 1g over 20mins, i.v, repeated
once if needed
Miscellaneous agents

52. Bradyarrhythmias
 Results from failure of impulse generation within SA node or failure of impulse
conduction through AV node
 Atrio-ventricular (A-V) block is due to depression of impulse conduction
through A-V node and bundle of His, mostly due to vagal influence or
ischaemia
 First degree A-V block: Slowed conduction resulting in prolonged P-R interval
 Second degree A-V block: Some supraventricular complexes are not
conducted: drop beats
 Third degree A-V block: No supraventricular complexes are conducted;
ventricle generates its own impulse; complete heart block

53. Bradyarrhythmias
 Definitive treatment - cardiac pacemaker
 Drugs are of value only for acute/transient A-V block
 Atropine: When A-V block is due to vagal overactivity, it can be improved by
atropine 0.6–1.2 mg i.m
 Sympathomimetics (isoprenaline): Overcome partial heart block by facilitating
A-V conduction and shortening ERP of conducting tissues
Also used in complete (3rd degree) heart block to maintain a sufficient
idioventricular rate till external pacemaker can be implanted

54. Choice & Use of Anti-arrhythmic Drugs
 Vigorous therapy is indicated when:
 Arrhythmia is life-threatening, e.g. sustained VT, torsades de pointes, VF.
 Arrhythmia is causing hypotension, breathlessness, activity limitation, CHF
 Palpitation is marked, e.g. in PSVT, sustained VT, AF, torsades de pointes.
 When simple arrhythmia may lead to more serious ones, e.g. after Ml
Therapy with class I and class IV antiarrhythmics – no survival benefit
Only propranolol and to some extent amiodarone reduce cardiovascular
mortality

55. Choice & Use of Anti-arrhythmic Drugs
 The selection of an antiarrhythmic in a patient depends on:
 ECG diagnosis
 Possible mechanism underlying the arrhythmia
 Mechanism of action and range of antiarrhythmic activity of the drug
 Pharmacokinetic profile of the drug
 Haemodynamic effects of the drug
 Aim - To improve cardiovascular function
 Restoring sinus rhythm
 Controlling ventricular rate
 Conversion to a more desirable pattern of electrical and mechanical activity

56. Atrial / Ventricular
extrasystole
Asymptomatic – no
treatment required
Symptomatic - β blocker
Atrial fibrillation
Definition:
Fast ectopic, irregular atrial
activity (350-600 bpm)
Ventricular rate ~ 100-150 bpm
Treatment:
1. Underlying heart disease – find
out cause
2. Rate control – 70-100 bpm
Acute therapy
β blocker:- esmolol
CCB:- verapamil
Acute AF (> 48 hours)
Transesophageal
echocardiogram
Don’t cardiovert immediately,
Warfarin for 3 weeks
Cardioversion
Warfarin for 4 weeks
Chronic AF (>6 months)
a. Rate control with β
blocker, CCB
b. ↓ Risk of ischemic
stroke
Aspirin / Warfarin based
on CHADS 2 score
If score ≥2 – warfarin
<2 – aspirin

57. Rhythm control

58. Wolf-Parkinson-White
Syndrome
Termination:
Cardioversion, Radiofrequency
ablation
Maintenance:
1. Narrow QRS -
Propafenone/procainamide
2. Wide QRS - Propafenone +
verapamil / propranolol or
Amiodarone / sotalol
PSVT
An attack of PSVT can be terminated by reflex vagal
stimulation through
1. Valsalva maneuver,
2. Splashing ice cold water on face,
3. Hyperflexion (head between knees), etc.
The drug of choice is adenosine (i.v.). Other
alternatives are i.v. verapamil / diltiazem / esmolol &
IV amiodarone
Prevent recurrences - oral therapy with verapamil,
diltiazem or propranolol
TOC – Radiofrequency ablation

59. Ventricular tachycardia :
Definition:
≥ 4 consecutive ventricular
extrasystole of > 100 bpm
Unstable VT:
Immediate DC shock f/b
Amiodarone (DOC) / Lidocaine /
procainamide (IV)
Prevention of recurrence /
sudden cardiac death:
Best method – Intracardiac
defibrillator
Alternative – Amiodarone /
Propranolol / Propafenone
Chronic Ventricular
tachycardia
Nonsustained VT:
Suppression -
Propranolol/amiodarone (oral)
Sustained VT:
Abolition - i.v. Amiodarone +
propranolol/ cardioversion/
propafenone / lidocaine (i.v.)
Maintenance therapy -
Amiodarone/sotalol
Ventricular fibrillation
Termination:
Defibrillation + amiodarone
(i.v.)
Recurrence prevention:
Amiodarone (oral) /
propranolol

60. Modernized Classification :
Class Subclass Pharmacological
Targets
Drug Clinical Application
0 Inhibition of If reducing
SA Node, phase 4 pacemaker
depolarization rate
Ivabradine Stable angina and
chronic
heart failure
I Ia,Ib,Ic
Id Reduction in late Na+ current Ranolazine Stable angina, ventricular
tachycardia
II IIa Nonselective
β inhibitors
IIb Isoproterenol
IIc Atropine, Sinus bradycardia
IId Carbachol,
pilocarpine,
IIe Adenosine

61. Modernized Classification :
Class Subclass Pharmacological
Targets
Drug Clinical Application
III IIIa ultrarapid K+ current
Blockers
Vernakalant Prolonged atrial AP
recovery, Increased
ERP, conversion of
atrial fibrillation
IIIb Opening of ATP-
sensitive K+ channels
Nicorandil,
pinacidil
IIIc BMS 914392
IV IVa Nonselective surface
membrane Ca2+
channel blockers
Bepridil Angina pectoris,
supraventricular
tachyarrhythmias
IVb-e

62. Modernized Classification :
Class Subclass Pharmacological
Targets
Drug Clinical Application
V Mechanosensitive
channel blockers
N-(p amylcinnamoyl)
anthranilic acid
Reduction in EAD-/
DAD-induced
triggered activity
VI Gap junction channel
blockers
carbenoxolone Reduction in
ventricular/atrial
Conduction, accessory
pathway
Conduction, AV node
conduction
VII Upstream target
modulators
ACE inhibitors, ARBs,
omega-3 FA, Statins
Reduction of
structural and
electrophysiological
remodeling changes
that compromise
AP conduction and
increase re-entrant
tendancy

63. Conclusion :
 Abnormal automaticity or impaired conduction or both is the cause of
cardiac arrhythmia
 Anti-arrhythmic drugs used to prevent or treat irregularities, themselves
may cause arrhythmias
 Asymptomatic atrial / ventricular extrasystole need not be treated
 Ventricular arrhythmias are most important cause of sudden cardiac death.
Therefore, should be monitored & treated in intensive coronary care unit

64. References :
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of Medical Physiology.1st edition.UP India,Elsevier;2009.p255-60
 HL Sharma & KK Sharma. Drug Therapy of Cardiac Arrhythmias. Sharma and
Sharma’s principles of Pharmacology. 4th edition. Hyderabad,Paras Medical
Publisher;2017.p296-314
 Robert D. Harvey, PhD, & Augustus O. Grant, MD, PhD. Agents Used in Cardiac
Arrhythmias. Basic & Clinical Pharmacology Bertram G. Katzung,14th edition.
McGraw-Hill Education; 2018. p228-254
 Nicholas A. Boon, Nicki R. Colledge & Brian A. Walker.Disorders of heart rate
rhythm & conduction.Davidson’s Principles & Practice of Medicine.23th
edition.Philadelphia,Chuhill Livingstone;2018.p441-75
 Circulation. 2018;138:1879–1896.DOI: 10.1161/CIRCULATIONAHA.118.035455