1. Dept. of Pharmacology Faculty of Medicine AIMST
Antiarrhythmic Drugs
Dept. of Pharmacology
Faculty of Medicine
AIMST

2. Antiarrhythmic Drugs Lecture Objectives
Cardiac Arrhythmias-What are they?
Antiarrhythmic Drugs-Classification (Vaughan Williams/Sicilian Gambit/Miscellaneous agents)
Pharmacology & uses of :
Class I agents (Quinidine/Lidocaine/Phenytoin)
Class II agents (Propranolol/Esmolol)
Class III agents (Amiodarone)
Class IV agents (Verapamil)
Miscellaneous agents (Digoxin/Adenosine)

3. Cardiac Arrhythmias Definition Disorders of within the heart
Rate
Rhythm
Impulse generation or
Impulse conduction
within the heart
Arrhythmias disruption of normal sequence of
myocardial activation
seriously compromising cardiac mechanical efficiency
reducing cardiac output

4. Antiarrhythmic Drugs Vaughan Williams Classification
Class I (Na+ channel blockers)
Ia (blocks conduction, ↑ERP)
Quinidine
Procainamide
Disopyramide
Ib (blocks conduction, ↓ERP)
Lidocaine
Mexiletine
Phenytoin
Ic (blocks conduction, no effect/↑ERP)
Encainide
Flecainide
Propafenone
Moricizine

5. Antiarrhythmic Drugs Vaughan Williams Classification
Class II (β-adrenoceptor blockers)
Propranolol
l -Sotalol
Esmolol
Class III (K+ channel blockers)
Amiodarone
Bretylium
d -Sotalol
N-acetyl-procainamide(Acecainide)
Dofetilide
Ibutilide

6. Antiarrhythmic Drugs Vaughan Williams Classification
Class IV (Ca2+ channel blockers)
Verapamil
Diltiazem
Bepridil

7. Antiarrhythmic Drugs Miscellaneous
Adenosine
Digoxin
Magnesium, etc.

8. Antiarrhythmic Drugs-Major Pharmacological & Electrophysiological Actions
Class I
Slowing/blocking conduction
Class II
↓ SA nodal automaticity
Sympatholytic activity
Class III
No effect on conduction
Delay repolarization
Class IV
Slows conduction velocity in AV node

9. Antiarrhythmic Drugs (Class Ia) Quinidine
Chemistry
Dextro isomer of the alkaloid quinine
Pharmacological Actions
Cardiac
Blocks Na+ channels
↓Phase 0 slope (atria/ventricles/Purkinje fibres)
↓Conduction velocity
↑ ERP → ↑ APD

10. Antiarrhythmic Drugs (Class Ia) Quinidine
Pharmacological Actions
Extracardiac
Quinidine → α-blockade→ Vasodilation
↑ SA node rate ↓ PVR
Quinidine
↓ conc. ↑ conc.
Indirect Direct effect
anticholinergic on cardiac myocytes
effects predominate

11. Antiarrhythmic Drugs (Class Ia) Quinidine
Pharmacokinetics
Rapidly absorbed from GIT
80% PPB
Hepatic metabolism
Renal excretion
Therapeutic Uses
Atrial Fibrillation
Atrial Flutter
PSVT
Premature Ventricular Contractions VT

12. Antiarrhythmic Drugs (Class Ia) Quinidine
Adverse Effects
Cardiac
AV block
↓ myocardial contractility
↑ cardiac ERP ↑ APD
↑ QT interval
↑ Ventricular tachyarrhythmias
(Torsades de pointes)
Quinidine Syncope

13. Antiarrhythmic Drugs (Class Ia) Quinidine
Adverse Effects
Cardiac
-ve inotropic action
↓ BP Cardiac failure
GIT
Nausea/Vomiting/Diarrhea
Cinchonism
Tinnitus/Headache

14. Antiarrhythmic Drugs (Class Ia) Quinidine
Drug Interactions
Quinidine increases plasma Digoxin concentrations (due to displacement from tissue binding + impairment of renal excretion)
DOSE OF DIGOXIN SHOULD BE DECREASED WHEN THE DRUGS ARE USED TOGETHER

15. Antiarrhythmic Drugs (Class I b) Lidocaine
Used principally for ventricular arrhythmias
Kinetics makes it unsuitable for oral administration (the drug undergoes extensive presystemic (first-pass) hepatic elimination)
Used by the i.v., or occasionally the i.m. route
Adverse reactions uncommon unless there is significant cardiac failure or infusion is rapid
Adverse effects include hypotension, dizziness, blurred sight, sleepiness, slurred speech, numbness, sweating, confusion and convulsions

16. Antiarrhythmic Drugs (Class Ib) Phenytoin
Orally active anticonvulsant
Antiarrhythmic properties similar to those of lidocaine
Used to treat ventricular arrhythmias, digitalis overdose-induced arrhythmias, and torsades de pointes

17. Antiarrhythmic Drugs (Class II) Propranolol
Pharmacological Actions
β-adrenergic receptor blocker
↓ myocardial contractility (-ve inotropic action)
↓ heart rate (-ve chronotropic action)
↓ Automaticity
↓ Phase 4 slope of diastolic depolarization
↓ AV conduction

18. Antiarrhythmic Drugs (Class II) Propranolol
Therapeutic Uses
Supraventricular arrhythmias
Re-entry arrhythmias
Digoxin-induced arrhythmias
Adverse Effects
Sedation/Sleep disturbances/Depression
Worsening of pre-existing asthma & other forms of airway obstruction
Severe hypotension/bradycardia/Heart block or cardiac arrest (from over dosage)
Heart failure

19. Antiarrhythmic Drugs (Class II) Esmolol
Pharmacological Actions
Very short-acting β1-selective blocker (half-life ~ 9 min)
Solely used in cardiac arrhythmias (for intraoperative & other acute arrhythmias)
Concomitant IV administration of calcium channel blockers that affect cardiac conduction (e.g. Verapamil, Diltiazem) may lead to intense bradycardia and risk of AV block

20. Antiarrhythmic Drugs (Class II & III) Sotalol
Pharmacological Effects
l-Sotalol β-adrenergic blocking activity
d-Sotalol Block K+ channels
↓ K+ outward current during repolarization
Prolong repolarization
↑ cardiac APD & ERP

21. Antiarrhythmic Drugs Sotalol (Class II & III)
Therapeutic Uses
Life-threatening ventricular arrhythmias
Maintenance of sinus rhythm in patients with atrial fibrillation
Treatment of supraventricular and ventricular arrhythmias in pediatric age group
Adverse Effects
Extension of its pharmacologic actions
Torsade de pointes (dose-dependent)

22. Antiarrhythmic Drugs (Class III) Amiodarone
Pharmacological Actions
Possess Class I, II, III & IV actions (broad spectrum)
Blocks K+ channels
Prolong repolarization
↑ ↑ cardiac APD & ERP

23. Antiarrhythmic Drugs (Class III) Amiodarone
Therapeutic Uses
Used in management of severe refractory atrial & ventricular tachyarrhythmias
Maintaining normal sinus rhythm in patients with atrial fibrillation (in low doses: mg/d)
Prevention of recurrent VT

24. Antiarrhythmic Drugs (Class III) Amiodarone
Side Effects
Symptomatic bradycardia/Heart block/Polymorphic VT
Reversible pulmonary fibrosis
Hepatitis
Corneal micro deposits (asymptomatic)/Optic neuritis/Blurred vision
Skin deposits/photodermatitis/gray-blue discoloration
Thyroid abnormalities

25. Antiarrhythmic Drugs (Class IV) Verapamil
Chemistry
Phenylalkylamine L-type Ca2+ channel blocker
Pharmacological Actions
↓ Ca2+ entry in pacemaker cells (SA & AV nodes)
↓ automaticity

26. Antiarrhythmic Drugs (Class IV) Verapamil
Pharmacological Actions (contd.)
↓ Ca2+ entry via L-type channels into cardiac myocytes
↓ myocardial contractility(-ve inotropic action)
↓ AV node ↓ Re-entry

27. Antiarrhythmic Drugs (Class IV) Verapamil
Therapeutic Uses
Supraventricular arrhythmias
Re-entrant supraventricular tachycardia
Reducing ventricular rate in Atrial Flutter/Atrial Fibrillation
Less effective in ventricular arrhythmias
Adverse Effects
Nausea/Constipation/Headache/Lassitude/
Hypotension/Bradycardia/Heart block

28. Antiarrhythmic Drugs- Digoxin
Therapeutic Uses
Atrial Fibrillation/Atrio-ventricular Nodal
Tachycardia
Digoxin ↑ ERP of AV node
↓ Cond. velo. at AV node
↓ ventricular rate
↓ fatal VF/VT
Paroxysmal Atrial Tachycardia

29. Antiarrhythmic Drugs- Adenosine
Chemical Nature
Endogenous purine nucleoside
Rapidly metabolized by circulating adenosine deaminase
Mechanism of Action
Activation of an inward rectifier K+ current
Hyperpolarization
Inhibition of Ca2+ current
Suppression of Ca2+ dependent action potentials

30. Antiarrhythmic Drugs Adenosine (contd.)
Pharmacological Actions
Brief residence in plasma (several seconds)
Slows/Inhibits AV nodal conduction
Increases AV nodal refractory period
Therapeutic Use
Prompt conversion of Paroxysmal Supraventricular Tachycardia to sinus rhythm (90-95% efficacy)
A-V Nodal Reentrant Tachycardia & A-V Reciprocating Tachycardia

31. Antiarrhythmic Drugs Adenosine (contd.)
Adverse Effects
Flushing (~ 20% patients)/Shortness of breath/Chest burning (perhaps related to bronchospasm)/High-grade AV block/ Headache/Hypotension/Nausea/Paresthesias
Drug Interactions
Adenosine less effective in presence of adenosine receptor blockers (e.g., Caffeine, Theophylline)
Potentiation of action in the presence of adenosine uptake inhibitors (e.g., Dipyridamole)

32. Antiarrhythmic Drugs Lecture Summary
Cardiac Arrhythmias-What are they ?
Antiarrhythmic Drugs-Classification
Vaughan Williams
Sicilian Gambit
Miscellaneous agents
Class I agents-Quinidine/Lidocaine/ Phenytoin
Class II agents-Propranolol/Esmolol
Class III agents-Amiodarone
Class IV agents-Verapamil
Miscellaneous- Digoxin/Adenosine

33. For Further Reading!..
Basic & Clinical Pharmacology by Bertram G. Katzung (9th Edition)(Chapter 14)
Clinical Pharmacology by D. R. Laurence, P. N. Bennett & M. J. Brown (9th Edition) (Chapter 24)
Goodman & Gilman’s The Pharmacologic Basis of Therapeutics (10th Edition)(Chapter 35)
Drugs for the Heart by Lionel H Opie & Bernard J Gersh (6th Edition)(Chapter 8)
Modern Pharmacology with Clinical Applications by Charles R Craig & Robert E Stitzel (6th Edition) (Chapter 16)