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DR.Dr. Endang Isbandiati Soediono, MS, SpFKDept.Pharmacology & Therapy, MedicalFaculty, AIRLANGGA UNIVERSITY

Dept.Clinical Pharmacology, Dr.Soetomo-Teaching HospitalSURABAYA

Class Major action I Na+ channel block II β – blockade III AP prolongation IV Ca2+ channel block

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Subgroup I A. Procainamide . Quinidine. Disopyramide Subgroup I B. Lidocaine. Mexiletine Subgroup IC . Flecainide. Popafenone. Moricizine FKeprwtnUNAIREIS09 3

Procainamide . cardiac : slow AP& conduction, prolong QRS directly depressant actions on SA

and AV nodes . extracardiac : ganglion blocking > reduce

PVR, hypotension Toxicity : cardiac > torsade de pointes

arrhythmia and syncope extracardiac > LE, arthralgia

and arthritis Therapeutic Use atrial and ventricular arryhtmia second choice of sustained VA assoc . MI

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Quinidine cardiac : slows AP&conduction, prolong QRS more antimuscarinic effects toxic conc.Quinidine > Na ch.

Block >> extracardiac : d, n, v, cinchonism,

immunologic r. PK : absorpsi per oral, albumin & α-acid

glycopr. Therapeutic Use : to maintain normal sinus rhytm pts. Atrial

flutter/fibrilation

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DisopyramideCardiac : very similar to Procainamide and

quinidine more antimuscarinicToxicityCardiac : neg. Inotropic > may precipitate HF > not use in pts. HFExtracardiac : Atropine-like activityPK : oral prep. 150 mg /3xd, reduce dose inrenal

impairement No loading dose (HF)Therapeutic UseVentricular arryhtmia

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LidocaineLow toxicity, high effective in arrythmia

assoc. W. Acute MICardiac : blocks activated and inactivated Na

channel > selective depression of conduction in depolarized cells

Toxicity :Cardiac least ;Hi.do. may cause hypotension ExtracardiacLike local anes. > paresthesia, tremor,

nausea, lighheadedness, slurred speechconvulsion most occur > elderly, bolus too

rapidSeizure : tx. Diazepam iv

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PK : first-pass effect >>Adult loading dose 150-200mg over 15 minutes (single infusion or a series of slow boluses) followed by maintenance infusion of 2-4mg/minMDT pl. Lidocaine : great valueMI and acute illness : higher α 1-acid glycoproteinHF : VD< & TBC< loading and maintenance <Liver dis. : usual loading do., increase maintenace do.Propranolol, Cimetidine : reduce clearance LidocaineTherapeutic UseAgent of choice : ventricular tachycardia and px. ventricular fibrillation after cardioversionMost : iv Lidocaine only to pts. w. Arryhtmia.

Mexiletine orally active therapeutic use : ventricular arrythmia daily do. 600-1200mg/d ADR : neurologic (tremor, blurred vision,

lethargy) Efficacy : relieving chronic pain due to

diabetic neuropathy and nerve injury

Flecainide potent blocker Na and K channelsVery effective in suppressing ventricular

contractionMay cause severe exacerbation of arrythmia to

pts. Preexisting ventricular tachyarrythmia and a previous MI and ventricular ectopy

Usual dose : 100-200mg twice a dayFKeprwtnUNAIREIS09 9

MoricizinePhenothyazine derv. : tx.

VentriculararrythmiaPotent Na channel blocker that does not

prolong AP durationMetabolite multiple, some active w. Long HLLike other potent Na channel blocker : can

exacerbate arrythmiaUsual do. 200-300mg by mouth three times

a day

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PropanololAntiarrythmic : β - blocker & direct membrane

effectPx. infarction and sudden death (after acute MI)

EsmololShort acting, antiarrythmic intraoperative and

other acute arrythmia.

SotalolNonselective - blocking that prolong AP (class III)

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Amiodarone po/iv : serious ventricular arrythmia also : supraventricular arrythmia (atrial fibrillation)Cardiac : marked prolong AP (and QT interval)Also blocks inactivated Na channel, weak adrenergic

and Ca channel blocker Slowing HR and AV node

conduction Extracardiac : peripheral vasodilatation Toxicity Cardiac : bradycardia and HB (Sinus or AV node dis.)

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Extracardiac : accumulates in many tissues (hearts 10 – 50 times greater than plasma), lung, liver, skin, tears

Dose-related pulmonary toxicity : fatal pulmonary fibrosis

Abnormal liver function test, photodermatitis, corneal microdeposit , halos

Hypothyroidism or hyperthyroidismPK : bioavailability 35- 65%, effects are maintain for

1-3months after discontinuation.Metabolism CYP3A4 : > by Cimetidine ; < by

RifampinEnzyme inhibitor : Digoxin and Warfarine >Therapeutic use: low do. (100-200mg/d) maintaining N sinus rythm

pts. atrial fibrilationPx. Recurrent ventricular tachycarduiaIncreases the pacing and defibrillation threshold.

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BretyliumLengthens the ventricular AP duration and

effective refractory periode (in ischemic cells)

at the onset of therapy : catecholamine positive inotropic action may precipitate ventricular arrythmia

Sympatophlegic action : postural hypotensionPK : iv use , bolus 5 mg/kg over 10 minutes,

may repeat after 30 minutesMaintenace tx. : every 4-6 hours bolus or

constant infusion of 0,5 – 2 mg/minTherapeutic UseRarely used, only when Lidocaine and

cardioversion failedFKeprwtnUNAIREIS09 14

Sotalol β- adrenergic blocker (class II): l-isomerAP prolonging (class III) : l- and d-isomer Well absorbed orallyRenal excretion, unchanged, HL 12 hoursDose related torsade de pointesTherapeutic UseLife-threatening ventricular arrythmias and

maintenance of sinus rythm (pts. atrial fibrillation)

Supraventricular and ventricular arrythmia in pediatric age group

Decrease threshold for cardiac defibrillationFKeprwtnUNAIREIS09 15

Dofetilide dose-dependent blockade effectBioavailability 100%Verapamil increase peak plasma dofetiliteCimetidine, inhibitor of the renal cation

secretion mechanism, prolong HL. Dosis must be based on the creatinine clearance

Tx. Use : maintenance N sinus rythm (pts. atrial fibrillation)

IbutilideIv for acute conversion of atrial fluuter and

atrial fibrillationADR : excessive QT interval prolongation and

torsade de pointesFKeprwtnUNAIREIS09 16

VerapamilBlocks activated and inactivated L-type Ca channelsActivation depend on the calcium current (SA and AV nodes)Extracardiac : peripheral vasodilatationToxicity Cardiac : dose related cardiotoxic effect; hi.do. AV blocks (pts. AV

nodal disease) > tx. Atropine and β - receptor stimulant Extracerdiac : constipation, lassitude, nervousness, and peripheral

edemaPK: Bioavalability 20% caution in hepatic dysfunctionAdult without HF or SA, or AV nodal dis. parenteral Verapamil

terminate supraventricular tachycardiaUse : initial bolus 5mg over 2-5 minutes, followed by a second 5mg

bolus Therapeutic Use : Supraventricular tachycardia; Reduce ventricular

rate in atrial fibrillation and flutter; Ventricular arrythmiaFKeprwtnUNAIREIS09 17

AdenosineMOA : activation K current and inhibition of

Ca currentDOC : prompt conversion of paroxysmal

supraventricular tachycardia to sinus rhythm

Use : bolus 6mg, followed by 2mg if neededAdenosine receptor blocker : Theophylline or

CaffeinAdenosine uptake inhibitor : Dipyridamole

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