This document discusses antiarrhythmic drugs and their mechanisms and classifications. It begins by defining arrhythmias as abnormalities in impulse formation or conduction in the heart muscle. It then discusses the cardiac action potential and the five phases. Antiarrhythmic drugs are classified based on their mechanisms of action on sodium, potassium, calcium, or beta receptor channels. Examples from each class (Class I-IV) are provided along with their indications, mechanisms, metabolism, dosing and side effects.

1. ANTI ARRYTHMIC DRUGS
Presented by: Dr Nayak Rakshat
Guided by: Dr Naresh Tyagi

2. What is an Arrhythmia?
• The arrhythmias are conceptually simple-
dysfunctions cause abnormalities in
– impulse formation (abnormal automaticity)
– conduction in the myocardium (reentry),
– or combination of both

3. Factors that precipitate arrhythmia
– Cardiac ischemia,
– Hypoxia,
– Acidosis, alkalosis
– Electrolyte disturbances
– Excessive catecholamine exposure
– Exposure to toxic substances
– Unknown etiology

5. 0 mV
-80 mV
-90 mV
OUTSIDE
MEMBRANE
INSIDE
Na+ K+
4
3
1
Ca++ K+
Atp
K+
Na+
K+
Ca++
Na+
K+
Na+
Resting
open
Phase zero
depolarization0
Early
+r3e0pmoVlarization
Inactivated
Plateau phase
2
Rapid
Repolarization
phase
Phase 4
depolarization

6. Cardiac Action Potential
• Divided into five phases (0,1,2,3,4)
– Phase 4 - Diastole depolarization
the resting membrane potential is maintain
by K+ efflux and slow Na+ & Ca2+ influx
• Except for the SA node.

7. • Addition of current into cardiac muscle
(stimulation) causes
– Phase 0 – rapid depolarization- opening of
fast Na+ channels
• Drives Na+ into cell (inward current),
changing membrane potential
• Transient outward current due to
movement of Ca+ and K+
Cardiac Action Potential

8. Cardiac Action Potentialn’t)
Phase 1 – initial rapid repolarization
• Closure of the fast Na+ channels
• it is followed by a brief and incomplete period
of repolarization.
• K+ efflux: This period is mediated by a
temporary movement of K+ from the
intracellular to the extracellular space.
• Ca+ influx.
• Phase 0 and 1 together correspond to the R
and S waves of the ECG

9. • Phase 2 - plateau phase
– sustained by the balance between Ca+ influx and K +
efflux
– Unique to the cardiac action potential
– Normally blocks any premature stimulator signals
(other muscle tissue can accept additional
stimulation and increase contractility in a
summation effect)
– This initiates a slow repolarization, and creates a
plateau in the action potential. Cardiac contraction
is mediated by phase 2.
– Corresponds to ST segment of the ECG.

10. • Phase 3 – rapid repolarization
– The calcium channels close. The process of
repolarization is accelerated.
– K+ channels remain open,
– Allows K+ to build up outside the cell, causing the
cell to repolarize
– K + channels finally close when membrane
potential reaches certain level
– Corresponds to T wave on the ECG

11. 
Classification of Cardiac antiarrhythmic drugs
Class I Class II Class III Class IV
Class 1A:
1. Quinidine
2. Procainamide
3. Disopyramide
4. Moricizine
Esmolol Amiodarone Verapamil
Class 1B:
1. Lidocaine
2. Tocainide
3. Mexiletine
Propranolol Sotalol Diltiazem
Class iC:
1. Flecainide
2. Propafenone
Acebutanol Ibutilide
Dofetilide
Bretylium

12. Classification of antiarrhythmics
(based on mechanisms of action)
• Class I – blocker’s of fast Na+ channels
– Subclass IA
• Cause moderate Phase 0 depression
• Prolong repolarization
• Increased duration of action potential
• Includes
– Quinidine – 1st antiarrhythmic used, treat both atrial and
ventricular arrhythmias, increases refractory period
– Procainamide - increases refractory period but side effects
– Disopyramide – extended duration of action, used only for
treating ventricular arrthymias
– Moricizine

13. Class IA Drugs
Quinidine
• It has antimalarial and antipyretic effects.
• But it has intense effects on the heart.
• It decreases the slope of phase 4
depolarization,which explains its effectiveness
in suppressing cardiac arrhythmias caused by
enhanced automaticity.

14. Metabolism and Excretion
• It is hydroxylated in the liver to inactive metabolites,
which are excreted in the urine.
• About 20% of quinidine is excreted unchanged in the
urine.
• The concurrent administration of phenytoin,
phenobarbital, or rifampin may lower blood levels of
quinidine by enhancing liver clearance.
• Because of its dependence on renal excretion and
hepatic metabolism for clearance from the body,
accumulation of quinidine or its metabolites may occur
in the presence of impaired function of these organs.

15. Adverse Effects
• Non cardiac – diarrhea
- Thrombocytopenia
-bone marrow depperesion
-lupus syndrome
Cardiac – QT interval prolongation
torsades de pointes

16. • Lesser vagolytic action , depression of
contractility & fall in BP
• Metabolized by acetylation to N-acetyl
procainamide which can block K+ channels
• Doesn’t alter plasma digoxin levels
• Use: Monomorphic VT, WPW Syndrome
procainamide

17. • Side Effects
– Cardiac- ventricular asystole or fibrillation in
patients with heart block
– Systemic lupus erythematosus like syndrome –
• usually arthralgia and arthritis.
• pleuritis, pericarditis or parenchymal
pulmonary disease may occur in some.
– GIT : Nausea , diarrhea
– Torsade de pointes
– Hypotension
– Drug fever or allergic rash

18. • Dosage –
– Oral: 50 mg/kg/d in Three divided doses ;
– IM: 0.5—1.0 g 8hrly
– IV: 500–600 mg over 25–30 min then 2–6 mg/min

19. Disopyramide
• Both VA & SVA (Treatment and Prophylaxis)
• Orally & I.V
• Very similar to Quinidine EXCEPT more
Negative inotropic and antimuscarinic effects
• Less side effects & allergy than Quinidine

20. adverse effects
• Cardiac toxicity similar to quinidine
• Torsade de points
• HF because of negative inotropic effects
• Antimuscarinic effects: dry mouth, urinary retention,
constipation,
• Contraindications: glaucoma, BPH,

21. Classification of antiarrhythmics
(based on mechanisms of action)
– Subclass IB
• Weak Phase 0 depression
• Shortened repolarization
• Decreased action potential duration
• Includes
– Lidocaine (also acts as local anesthetic) – blocks Na+ channels
mostly in ventricular cells, also good for digitalis-associated
arrhythmias
– Mexiletine - oral lidocaine derivative, similar activity
– Phenytoin – anticonvulsant that also works as antiarrhythmic
similar to lidocaine
– Tocainide

22. CLASS IB
LIDOCAINE
• Pharmacokinetics
– very extensive first-pass hepatic metabolism, only
3% of orally administered drug appears in the
plasma
– Given only by I.V. route
– Excreted via kidney .
– Half-life 2hrs.

23. LIDOCAINE
• Side Effects
– Cardiac - one of the least cardiotoxic of the currently used
sodium channel blockers. Arrhythmias are uncommon
– Neurologic - parasthesias, tremor, nausea of central origin,
light-headedness, hearing disturbances, slurred speech,
and convulsions.

24. -
• Therapeutic Use
– Mainly used for suppression of ventricular arrhythmias
– Drug of choice for management of ventricular arrhythmias,
particularly those induced by myocardial infarction or
cardiac surgery
– no value in the treatment of atrial arrhythmias
– Dose- loading dose of 150–200 mg administered over
about 15 minutes followed by a maintenance infusion of
2–4 mg/min
– Dose should be decreased in heart failure and liver disease

25. Mexiletine
• Oral analogue of lidocaine
• No first pass metabolism in liver
• Use:
– chronic treatment of ventricular arrhythmias
associated with previous MI
– Unlabelled use in diabetic neuropathy
• Tremor is early sign of mexiletine toxicity
• Hypotension, bradycardia, widened QRS ,
dizziness, nystagmus may occur

26. Tocainide
• Orally effective amine analogue of lidocaine
• Used for chronic suppression of ventricular cardiac
tachyarrhythmias.
• Adult dose is 400-800mg administered every 8hours.
• Side effects resemble those of mexiletine
• In rare patients, tocainide has caused severe bone
marrow depression ( leukopenia, anemia,
thrombocytopenia) and pulmonary fibrosis
• As with mexiletine, the combination of tocainide with a
beta-adrenergic blocker or another antidysrhythmic drug
has a synergistic effect

27. Classification of antiarrhythmics
(based on mechanisms of action)
– Subclass IC
• Strong Phase 0 depression
• No effect of depolarization
• No effect on action potential duration
• Includes
– Flecainide (initially developed as a local anaesthetic)
» Slows conduction in all parts of heart,
» Also inhibits abnormal automaticity
– Propafenone
» Also slows conduction
» Weak β – blocker
» Also some Ca2+ channel blockade

28. flecainide
• Dose:
– Oral 100-400 mg 2 times daily.
• Pharmacokinetics and Metabolism:
T ½ 13-19 h.
Hepatic renal excretion unchanged
• Indications:
• very effective in suppressing premature ventricular
contractions
• currently used for patients with normal hearts who
have supraventricular arrhythmias
• Chronic treatment not recommended as increased
incidence of sudden death
• Reserved for treatment of life threatening arrhythmias
Subclass IC

29. • Contraindications:
– Patients with structural heart disease
– Patients with right bundle branch block and left
anterior hemiblock
– In the sick sinus syndrome, when the left ventricle is
depressed, and in the postinfarct state
• Side effects:
– QRS prolongation.
– Proarrhythmia.

30. Propafenone
• Dose:
– Oral 150-300 mg 3 times daily.
Pharmacokinetics and Metabolism:
– T ½ variable 2-10 h, up to 32 h in nonmetabolizers.
– Level 0.2-3 mcg/mL.
Indications:
– Life-threatening ventricular arrhythmias
– Suppression of supraventricular arrhythmias,
including those of WPW syndrome and recurrent
atrial flutter or fibrillation.
•
•

31. •
Contraindications:
– preexisting sinus, AV or bundle branch
abnormalities
– depressed left ventricular (LV) function.
– Patients with asthma and bronchospastic disease
including chronic bronchitis
Side effects:
– QRS prolongation.
– Modest negative inotropic effect.
– Proarrhythmia.
•

32. Class II – β–adrenergic blockers
– Based on two major actions
1) blockade of myocardial β–adrenergic
receptors↓cAMP  ↓ both Na+ & Ca+ current
2)Direct membrane-stabilizing effects related to Na+
channel blockade
↓both automaticity & HR and suppression of abnormal
pacemaker activity
• TheA
V node is particularly sensitive to β-blockers
• The PR interval is usually prolonged by β-blockers

33. M.O.A Beta blocker
4

34. Beta adrenergic blockers-
• Effective for cardiac arrhythmias , enhanced activity of
Sympathatic nervous system.
• For controlling ventricular rate in AF and AFL.
• Multifocal atrial tachycardia may respond to esmolol or
metoprolol (but best treated by amiodarone)
• Acebutolol for the t/t of frequent PVC.
• Propranolol is effective in controlling torsades de
pointes for pts with prolonged QTc
• Acebutolol,propranolol,metoprolol approved for
prevention of sudden cardiac death following MI.

35. Metabolism and excretion-
• Oral propranolol metabolised in liver
• Propranolol readily crosses BBB.
• Elimination t ½ propranolol= 2-4 hrs
• Antiarrhythmic activity persists for 6-8 hrs.

36. Dose-
• Propranolol 10-80 mg every 6-8 hrs
• Effective beta blockade when resting heart
rate is 55-60 bpm
• Propranolol IV 1 mg/min (3-6 mg)
• Onset of action-within 2-5 min,peak effect at
AV Node in 10-15 min,duration of action= 3-4
hrs.

37. Side effect
• Bradycardia, myocardial depression, hypotension, and
bronchospasm
• nausea, drug fever, allergic rash, increase oesophageal
reflux, cold extremities, worsening of Raynaud’s ds.
• Not to be used in pts with pre existing AV heart block.
• Hypoglycaemia in DM pts.
• CNS= mental depression and fatigue.

38. Classification of antiarrhythmics
(based on mechanisms of action)
• Class III – K+ channel blockers
– Developed because some patients negatively sensitive to
Na channel blockers (they died!)
– Cause delay in repolarization and prolonged refractory
period
– Includes
• Amiodarone – prolongs action potential by delaying K+ efflux but
many other effects characteristic of other classes
• Ibutilide – slows inward movement of Na+ in addition to delaying K
+ influx.
• Bretylium – first developed to treat hypertension but found to also
suppress ventricular fibrillation associated with myocardial
infarction
• Dofetilide - prolongs action potential by delaying K+ efflux with no
other effects
• Sotalol

39. Amiodarone
• Iodine containing long acting drug
• Mechanism of action: (Multiple actions)
–Prolongs APD by blocking K+ channels
–blocks inactivated sodium channels
–β blocking action , Blocks Ca2+ channels
–↓ Conduction, ↓ectopic automaticity

40. Dose
• Oral loading dose 1200-1600 mg daily; maintenance
200-400 mg daily
IV 150 mg over 10 min, then 360 mg over 6 h, then 540
mg over remaining 24 h, then 0.5 mg/min.
After cardiac surgery, 5 mg/kg over 20 minutes, 500 to
1000 mg over 24 hours, and then 0.5 mg/minute
Caution: Be aware of the risk of hypotension with
intravenous amiodarone.
Generally, intravenous amiodarone is used for 48 to 96
hours while oral amiodarone is instituted.
•
•
•
•

41. Pharmacokinetics
• T ½ 25-110 days (up to 6 months)
• The therapeutic range 1-2.5 mcg/mL.
• Hepatic metabolism.
• Lipid soluble with extensive distribution in body.
Because of this, amiodarone must fill an
enormous peripheral-tissue depot to achieve
adequate blood and cardiac concentrations.
• Excretion by skin, biliary tract, lachrymal glands.

42. Indications
• VT
• VF
• AF, Atrial flutter: Amiodarone is probably the
most effective of the available drugs to prevent
recurrences of paroxysmal AF or flutter and
reasonable choice for patients with structural
cardiac disease or CHF
• Other SVTs

43. Contraindications
• Severe sinus node dysfunction with
marked sinus bradycardia or syncope
• Second- or third-degree heart block
• Known hypersensitivity
• Cardiogenic shock
• Severe chronic lung disease.

44. Side effects
•
•
•
•
•
Sinus bradycardia (in older adults)
QT prolongation
Hypothyroidism
Hyperthyroidism
Pulmonary toxicity (very rarely occurs
with the low doses of about 200 mg
daily)
Hepatotoxicity (elevated enzyme levels,
hepatitis and cirrhosis)
Optic neuropathy/neuritis
Blue-gray skin discoloration
Photosensitivity
Peripheral neuropathy
Testicular dysfunction
•
•
•
•
•
•

45. Recommended preventative
actions
• baseline and 6-monthly thyroid function
tests and liver enzymes
• baseline and yearly ECG and chest
radiography
• physical examination of skin, eyes, and
peripheral nerves if symptoms develop

46. Sotalol
• Racemic mixture of D and L-Sotalol.
• At low doses= Non selective beta adr antagonist
• At high doses= prolongs cardiac action potential in
atria,ventricles and accessory bypass tracts.
• All beta blocking prop. d/t L isomer.
• Action potential prolongation d/t both D and L
isomers.
Pharmacokinetics-
• Excreted by the kidneys,dosing intervals
lengthened in pts with renal dysfunction.
• Doesn’t bind to plasma protein, doesn’t cross BBB
• Dose= 240-320 mg twice daily.

47. Side effect:
• Most dangerous s/e-torsades de pointes; dose
related.
• Dec.myocardialcontractility,bradycardia,
delayed conduction of cardiac impulses
through AV node
• Fatigue,dyspnoea,vertigo,nausea.

48. Calcium channel blockers (Class IV)
• Inhibit the inward movement of calcium
↓ contractility, automaticity , and AV conduction.
• Verapamil & diltiazem
• slow rate of AV-conduction in patients with atrial
fibrillation
• Verapamil – blocks Na+ channels in addition to Ca2+; also
slows SA node in tachycardia
Suppression of SA node; bradycardia
Slowing of AV node: abolish AV reentry
• Diltiazem
Class IV: Drug of choice for : A flutter and fibrillation

49. M.O.A calcium channel blocker
4
4

50. Verapamil
VERAPAMIL
synthetic derivative of papaverine.
Verapamil blocks both activated and inactivated type
calcium channels
Mechanism-
• Inhibit the flux of calcium ions across the slow
channels of vascular smooth muscle and cardiac
cells.
• Decrease rate of spontaneous phase 4
depolarization.
• Substantial depressant effect on AV node and a
negative inotropic effect on cardiac muscles
• Moderate degree of vasodilation of coronary
arteries and systemic arteries.

51. Metabolism and excretion-
70 % verapamil eliminated by kidneys, 15 % in bile
Large oral dose is needed bcoz of extensive hepatic 1st
pass metabolism after oral administration.
Dose-
For PSVT- 5 – 10 mg IV (75-150 mcg/kg) over 1- 3 min.
Followed by continuous infusion at the rate of 5
mcg/kg/min.
Ca gluconate 1 g IV,5 min before verapamil dec
verapamil induced hypotension.

52. Diltiazem-
Pharmacokinetics-
Oral bioavailability- 25-50 %
Peak concentrations achieved between- 30-60 min.
Elimination t ½- 2-6 hrs.
Hepatic metabolism; hepatic ds may require decreased dosing,
while renal failure does not affect dosing.
Dose-
IV-0.25 mg/kg bolus f/b 0.15 mg/kg/hr
Oral- 30-90 mg tid or qid.

53. Other drugs

55. Adenosine
• It is a first-line agent for terminating narrow complex
PSVTs
Dose:
– For paroxysmal SVT, initial dose 6 mg by rapid IV. If the dose is
ineffective within 1 to 2 minutes, 12 mg may be given and if
necessary, 12 mg after a further 1 to 2 minutes.
– The initial dose needs to be reduced to 3 mg or less in patients
taking verapamil, diltiazem, or b-blockers or dipyridamole or in
older adults at risk of sick sinus syndrome
T ½: 10-30 seconds.
•
•

56. • Indications:
– Paroxysmal narrow complex SVT (usually AV nodal
reentry or AV reentry such as in the WPW syndrome
or in patients with a concealed accessory pathway).
– In wide-complex tachycardia of uncertain origin,
adenosine can help the management by
differentiating between VT or SVT (with aberrant
conduction)
• Contraindication
– In asthmatic,
– Second- or third-degree AV block,
– Sick sinus syndrome.

57. • Side effects:
– nausea
– light-headedness
– headache
– flushing
– bronchospasm
– provocation of chest pain
– sinus or AV nodal inhibition
– bradycardia
– and with large dose infusion rare side effects
hypotension, tachycardia

58. Magnesium-
Originally used for pts with digitalis induced arrhythmias who
were hypomagnesemic
Influences Na-K ATPase, Na channels, certain K channels,
Calcium channels.
Use-
Indicated in pts with digitalis induced arrhythmias if
hypomagnesemia is present
Indicated in pts with torsades de pointes even if serum Mg is
normal.
Dose-
1g Magnesium sulphate IV over 20 min.

59. Digitalis
Used for stabilization of atrial tachydysrhythmias.
Vagolytic= slow conduction of cardiac impulses through AV
Node= slowing of ventricular response rate in pts with AF.
Enhance conduction of cardiac impulses through accessory
bypass tracts; so it can inc. the ventricular response rate in pts
with WPW Syndrome.
Dose-
Oral dose 0.5-1 mg in divided doses over 12-24 hrs.
Toxicity-
Any cardiac dysrhythmia may occur (m/c atrial tachycardia with
block)

60. 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

61. Thank you