Dr. Md.Toufiqur Rahman

MBBS, FCPS, MD, FACC, FESC, FRCPE, FSCAI, FAPSC, FAPSIC, FAHA, FCCP, FRCPG

Associate Professor of Cardiology

National Institute of Cardiovascular Diseases(NICVD),

Sher-e-Bangla Nagar, Dhaka-1207

Consultant, Medinova, Malibagh branchHonorary Consultant, Apollo Hospitals, Dhaka and

STS Life Care Centre, Dhanmondi drtoufiq19711@yahoo.com

Anti Arrhythmic Drugs 1

Class-1 Antiarrhythmic agents

Introduction· Arrhythmias require treatment either for alleviating

significant symptoms or for prolonging survival.

· Arrhythmias should be treated by drugs whose prophylactic

power out weighs the adverse effects. (as may be the case for

B-Blockers and amiodarone)

· Cheifly the class-III and class-I (especially class IC) agents

are proarrhythemic.

Modified Vaughan Williams: based on EP properties According to site of action

Classifications of antiarrhythmic agentsModified Vaughan Williams

Modified Vaughan Williams

I. Membrane-stabilizing,

II. Inhibit sympathetic stimulation

III. Delayed repolarization

IV. Calcium antagonists.

A. Quinidine Disopyramide Procainamide

B. Lidocaine Mexiletine Phenytoin Tocainide

C. Flecainide Lorcainide Encainide Propafenone

Beta-blockers

Amiodarone Bretylium Bethanidine Sotalol

Verapamil

Diltiazem

According to their site of action

Sinus node, atrium

Beta-blockers

Digoxin

Disopyramide

Quinidine

Amiodarone

Procainamide

Verapamil

Atrioventricular nodeDigoxin

Deta-blockers

Verapamil

Diltiazem

Encainide

Flecainide

Lorcainide

Propafenone

Accessory pathwayDisopyramide

Amiodarone

Flecainide

Procainamide

VentricleLidocaine, lignocaine

Procainamide

Disopyramide

Beta-blockers

Amiodarone

Mexiletine

Quinidine

Phenytoin

Tocainide

Drugs

Quinidine

Procainamide

Disopyramide

Antiarrhythmic action

·Act chiefly by

inhibiting the fast

sodium channel with

depression of phase

‘0’ of action potential.

·Prolong the action

potential duration

Pro-arrhythmic

action· High·Prolonging the QT

interval·depressing

conduction·Promoting reentry

·NIL

·NIL

Use Atrial fibrillation/A flutter

Supraventricular /Ventricular arrhythmias

SVT, life threatening ventricular arrhythmia

Summary of class 1 drugs

Lidocaine

Tocainide

Mexiletine

Phenytoin

Flecainide

Propafenone

Moricizine

Inhibit fast Na-channel* Shortening action potential duration in non-diseased fissue* Promote conduction block thereby interrupting reentry circuits selectively on diseased or ischemic tissue.

(1) Powerful inhibitor of fast Na+channel(2) Marked inhibitory effect on His-purkinje conduction with QRS widening.(3) Markedly shorten AP duration of only purkinje fibre

·NIL

High

·Moderate

·Moderate

Drugs Antiarrhythmic

action

Pro-arrhythmic action Use

vent arrhythmia associated with AMI and cardiac surgeryOnly indicated for symptomatic ventricular arrhythmias that refractory to. (quinidine, procainamide, propranolol)

ventricular arrhythmias

(1) In digitalis toxic arrhythmias(2) Ventricular arrhythmias occouring after congenital heart

surgery.(3) Congenetial prolong QT syndrome(4) epilepsy and arrhythmias.

supra ventricular and ventricular arrhythmias For both supra ventricular and ventricular arrhythmias

life threatening ventricular and ventricular arrhythmias

Disopyramide (norpace,Rythmodan)

· Like quinidine· Strong anticholinergic· Half life 8 hours

Dose: loading dose 300mg 100-200 mg/6hrsLong acting 12 hrs dosing

Indication: SVT, life threating venticular arrhythmiaSide effects: Negative ionotnopic effect Anti cholynergric QT Prolongation

ContraindicationCHF , prolonged QT, Hypotension, glucoma.

Class IB Inhibit fast Na-channel

Shortening action potential duration in non-diseased fissue

Promote conduction block thereby interrupting reentry circuits

selectively on diseased or ischemic tissue.

· In effective in atrial arrhythmias (since AP dunation short in atria)

Lidocaine· Standard I/V agent for vent arrhythmia associated with AMI

and cardiac surgery· Prophylactic use to prevent VT, VF in AMI now

outmoded.· No role in chronic recurrent ventricular

arrhythmia.· Act preferentially on ischemic myocardium· More effective in presence of high external

potassium.

Pharmacokinetics· Rapidly deethylated by liver microsomes· By two critical factor

Liver blood flow Enzyme inducers

Rapidly distributed with in minutes, must be a subsequent infusion to maintain blood level.

Dose: Loading dose 75-100 mg I/V

After 30 minute 2nd loading doseThen 2-4 mg/min for 24-30 hours.

Lidocaine

Contraindication· Bradycardia or· Bradycardia & vent, arrhythmia

Side effects

· Free of haemodynamic side effects even Pts with CHF· Numbness, speech disturbence, dizziness.

Lidocaine

Lidocaine failureIf lidocaine apparently fails see for hypokalaemia measure blood level infusion level cautiously till CNS side effects. Class IA agents tried (procainamide) before amiodarone.

· Ist line recommandation for sustained VT· Efficacy of lidocaine low (15 to 20%) [procainamide 80%]

Mexiletine Used chiefly against ventricular arrhythmias. Choices as a firstline agent because.

Efficacy comparable to quinidineLittle/No haemodynamic depressionNo QT prolongationNo vagolytic effects

Dose: Oral looding dose 400mg then 300-1200 mg/day in three divided doses (with food/ antacid)I/V dose 100-250 mg at 12.5 mg/min

Then 2mg/kg/hour for 3.5 hourThen 0.5 mg/kg/hour as long as needed.

Side effects Dizziness, disorientation,

brady cardia, hypotension

Contrainidication: cardiogenic shock, 20

or 30 AV blockCan be given in combination with quinidine.

Mexiletine

In CAP study in 1989 Encainide and flecainide were removed because they had been found to increase mortality rate two to three folds.

In CAST II trail in 1991 it was found that moricizine was also producing similar trend towards harm.

CAST labeled all Na channel blockers as more restrictive groups of drugs.Pro-arrhythmic effects seen in CAST (Flecainide), CAST II (Moricizine) CASH (Propafenone) trial

Mexiletine

Side effects

Pul infiltrateGingivitisMacroytic anenia.

Class IC agentsPro-arrhythmic effects seen in CAST (Flecainide), CAST II (Moricizine) CASH (Propafenone) trial

Three major electro physologic effects (1) Powerful inhibitor of fast Na+channel(2) Marked inhibitory effect on His-purkinje conduction with

QRS widening.(3) Markedly shorten AP duration of only purkinje fibre

Mexiletine

FlecainideFor both supra ventricular and ventricular arrhythmias [including wpw syndrome, paroxysmal AF/A. Flutter]

Dose For VT100 mg twice daily increased every 4

days by 50 mg twice daily to a maximum of 400 mg daily.

For SVT or AF/A Flutter50 mg twice daily up to 300 mg daily.

Contraindication· Patient with structural heart disease· RBBB· Post – infarct state.

Propafenone· For ventricular and supraventricular arrhythmias· Dose 150-300 mg /3 times daily

(max 1200 mg)

Flecainide

Contraindication

Structural heart disease

depressed Left ventricular function

Bronchial Asthma

BBB

Flecainide

Moricizine

Both class IB and class IC properties

In AV nodal reentrant tachycardia slows retrograde

conduction

Tachycardia in WPW syndrome

refractoriness in reentrant limb

Dose 600-900 mg/In 3 divided doses.

Class IA(Quinidine, disopyramide procainamide)

Mechanism of action·Act chiefly by inhibiting the fast sodium channel with depression of

phase ‘O’ of action potential.

·Prolong the action potential duration

·Can cause proarrhythmic complications by:

·Prolonging the QT interval

·depressing conduction

·Promoting reentry

Moricizine

Quinidine· Wide spectrum of activity against reentrant, ectopie atrial

and ventricular tachy arrhythmias· Slows conduction and increases refractoriness in

retrograde fast pathway limb of AV nodal tachycardias and over accessory pathway.· Slows ventricular response to AF in WPW syndrome.· Inhibits peripheral and myocardial & - receptor may cause hypotension

Metabolized by liverMean bioavailability 90%Therapeutic blood level 2.3 – 5 mg/ml

IndicationsPharmacologic conversion of AF/A flutter (Drug of choice class III agents) with verapamil/DigoxinDose 300-400 mg/every 6 hours. (max – 2gm)

Contraindications·QT prolong ation QRS prolongation.·Clinical CHF·SSS·Myasthenia gravis

Quinidine

Side effects ·Diarrhoea, Nauses, headache, diffiness.

Drug Interactions* Digoxin Digoxin level·Other Type I negative ionotropic effect·B-Blocker hypotension·Amiodarone risk of torsades, Quinidine level·Warferin Anticoaglation.

Quinidine

Procainamide·Supraventricular /Ventricular arrhythemias ·May given I/V if lidocaine fails·Prolong QT but not as much as quinidine ·Renal excretion·Half life 3.5 hrs.

· Dose looding dose 1 gm 500 mg/3 hrs· slow release 500 – 1500 mg /6hrs.· I/V 100mg/2min 25 mg/min (max 1 gm in 1 hour)

2-6 mg/min.

* Side effects Arthralgia, rash, lupus syndrome, agranulocytosis· Contraindication RF, shock, myasthenia.

Tocainide·Oral analog of lidocaine, Now limited use.

·Neutropenia, agranulocytosis, severely limit its use

· Only indicated for symptomatic ventricular arrhythmias

that refractory to. (quinidine, procainamide, propranolol)

· Dose 300 - 600 mg/3 times daily.

Phenytoin (Diphenylhydantoin) Has four specific uses(1)In digitalis toxic arrhythmias (maintain AV conduction in the

presence of hypokalaemia)(2) Ventricular arrhythmias occouring after congenital heart

surgery.(3) Congenetial prolong QT syndrome (when B-blocker failed)(4) Patient with epilepsy and arrhythmias.

Dose I/V 10-15 mg/kg over 1 hour then oral 400-600 mg/day

Thank Youdrtoufiq19711@yahoo.com

Asia Pacific Congress of Hypertension, 2014, February

Cebu city, Phillipines

Seminar on Management of Hypertension, Gulshan, Dhaka