anti arrhythmic drugs 1 toufiqur rahman
TRANSCRIPT
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 [email protected]
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 [email protected]
Asia Pacific Congress of Hypertension, 2014, February
Cebu city, Phillipines
Seminar on Management of Hypertension, Gulshan, Dhaka