Circus MovementCircus Movement

Classification of Classification of antiarrhythmic drugsantiarrhythmic drugs

According to Vaughn-Williams According to Vaughn-Williams Classification:Classification:

• ClassClass 11: Sodium channel blockers: Sodium channel blockers• Class11Class11: : ββ- adrenoceptor blockers - adrenoceptor blockers • ClassClass 111111: Potassium channel : Potassium channel

blockersblockers

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• ClassClass 1V1V : Calcium channel : Calcium channel blockersblockers

Miscellaneous antiarrhythmic Miscellaneous antiarrhythmic agentsagents

Antiarrhythmic DrugsAntiarrhythmic Drugs

• Act on open or inactivated channelsAct on open or inactivated channels

( ( Use -dependence or State –Use -dependence or State –dependence)dependence)

• Have better effect in tissues that are Have better effect in tissues that are depolarized depolarized

Sodium channel blocking Sodium channel blocking drugsdrugs

• Classified into 3 classes according Classified into 3 classes according to interaction with sodium channels to interaction with sodium channels ::

• ClassClass 1A1A : intermediate interaction: intermediate interaction• Class1BClass1B : rapid interaction : rapid interaction• Class1CClass1C: slow interaction : slow interaction

Drugs of Class 1 A Drugs of Class 1 A

• QuinidineQuinidine is the prototype of this is the prototype of this classclass

• ProcainamideProcainamide

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• They possess intermediate rate of They possess intermediate rate of association and dissociation with association and dissociation with sodium channelssodium channels

• Having K+ channel blocking effect. Having K+ channel blocking effect. • Are used in treatment of atrial & Are used in treatment of atrial &

ventricular arrhythmiasventricular arrhythmias

Effect on action potentialEffect on action potential

• Slow phase 0Slow phase 0• Prolong phase 3Prolong phase 3• Result in :Result in :• Prolong the duration of action Prolong the duration of action

potential & effective refractory period potential & effective refractory period for both atria & ventriclesfor both atria & ventricles

• Decrease the slope of phase 4Decrease the slope of phase 4

QuinidineQuinidine

• Given only orallyGiven only orally• Has :Has :Atropine like actionAtropine like actionαα- adrenergic blocking effect- adrenergic blocking effect

Clinical usesClinical uses

• Atrial flutter & Atrial fibrillation it Atrial flutter & Atrial fibrillation it returns the rhythm back to normal returns the rhythm back to normal sinus rhythm.sinus rhythm.

• Used in treatment of ventricular Used in treatment of ventricular arrhythmias.arrhythmias.

Cardiac adverse effectsCardiac adverse effects A)A) Paradoxical ventricular tachycardiaParadoxical ventricular tachycardia

in atrial flutter or fibrillationin atrial flutter or fibrillation

* Quinidine shorten A-V refractory period * Quinidine shorten A-V refractory period by its atropine- like effectby its atropine- like effect

(So, Digoxin is given before quinidine)(So, Digoxin is given before quinidine)

B) A-V block at high plasma levelB) A-V block at high plasma level

C) Torsade de pointesC) Torsade de pointes

Extracardiac adverse Extracardiac adverse effectseffects

• HypotensionHypotension

• CinchonismCinchonism (headache, tinnitus, (headache, tinnitus, blurred visionblurred vision

• GIT( diarrhea, nausea,vomiting)GIT( diarrhea, nausea,vomiting)

Drug interactionsDrug interactions

Quinidine Quinidine increase increase the plasma level the plasma level of digoxin by displacing digoxin of digoxin by displacing digoxin from plasma protein binding sites from plasma protein binding sites and decreased digoxin renal and decreased digoxin renal clearance.clearance.

ProcainamideProcainamide

• Given safely by I.M. or I.V. routes .Given safely by I.M. or I.V. routes .• Metabolized in liver , giving an active Metabolized in liver , giving an active

metabolite (NAPA) has potassium metabolite (NAPA) has potassium channel blocking effect.channel blocking effect.

Procainamide(cont.)Procainamide(cont.)

• More effective in ventricular arrhythmias More effective in ventricular arrhythmias ..

• It is the second drug of choice after It is the second drug of choice after lidocaine in the treatment of acute lidocaine in the treatment of acute ventricular tachycardia associated with ventricular tachycardia associated with an acute myocardial infarctionan acute myocardial infarction

Adverse effectsAdverse effects

• Systemic lupus erythematosus like Systemic lupus erythematosus like syndrome.syndrome.

• Torsade de pointesTorsade de pointes

Class 1BClass 1B

• Shorten phase 3 repolarization Shorten phase 3 repolarization &duration of action potential &duration of action potential

• Suppress arrhythmias mainly due Suppress arrhythmias mainly due to ectopic focusto ectopic focus

• Show rapid association & Show rapid association & dissociation with Na dissociation with Na ++ channels. channels.

Drugs of Class 1BDrugs of Class 1B

• LidocaineLidocaine• Given only by intravenous routeGiven only by intravenous route

Therapeutic usesTherapeutic uses

First drug of choice in the treatment of First drug of choice in the treatment of acute ventricular tachycardia associated acute ventricular tachycardia associated with acute myocardial infarctionwith acute myocardial infarction

Adverse effectsAdverse effects

• Neurological effects :Neurological effects :

Tremors , nausea of central origin, Tremors , nausea of central origin, convulsions.convulsions.

MexiletineMexiletine

• Effective orallyEffective orally• Long half-lifeLong half-life• Mexiletine is used in chronic Mexiletine is used in chronic

treatment of ventricular treatment of ventricular arrhythmias.arrhythmias.

Adverse effectsAdverse effects

• Neurologic effects as lidocaineNeurologic effects as lidocaine

Class1CClass1C

• Interact slowly with sodium channelsInteract slowly with sodium channels• Markedly slow phase 0Markedly slow phase 0

• No effect on the duration of action No effect on the duration of action potential& refractory period.potential& refractory period.

Uses of Class 1C DrugsUses of Class 1C Drugs

• Flecainide Flecainide Only approved for refractory ventricular Only approved for refractory ventricular

arrhythmias.arrhythmias.

• Propafenone Propafenone Has weak Has weak ββ-blocking activity-blocking activityUsed in atrial flutter or fibrillation return Used in atrial flutter or fibrillation return

rhythm to normal sinus rhythmrhythm to normal sinus rhythm

Toxicity of Class 1 CToxicity of Class 1 C

• Severe proarrhythmic drugsSevere proarrhythmic drugs• Life- threatening ventricular Life- threatening ventricular

tachycardiatachycardia• FlecainideFlecainide increase the mortality increase the mortality

rate in patients with premature rate in patients with premature ventricular contractions following ventricular contractions following myocardial infarction.myocardial infarction.

Class 11: Class 11: ββ-drenoceptor -drenoceptor blocking drugsblocking drugs

• Decrease heart rate & cardiac Decrease heart rate & cardiac contractilitycontractility

• Suppress abnormal automaticity & Suppress abnormal automaticity & prolong A-V conductionprolong A-V conduction

Uses of Class 11 DrugsUses of Class 11 Drugs

1- Effective in atrial & ventricular 1- Effective in atrial & ventricular arrhythmias that associated with arrhythmias that associated with

Increased sympathetic activity Increased sympathetic activity ( ( High catecholamine states High catecholamine states )) 2-With quinidine in A.F.& A.F.2-With quinidine in A.F.& A.F. 3- Effective in preventing post infarct 3- Effective in preventing post infarct

arrhythmias as premature ventricular arrhythmias as premature ventricular contraction ,they increase survival ratecontraction ,they increase survival rate

Class 11 DrugsClass 11 Drugs

o PropranololPropranolol – Is used to reduce the sudden arrhythmic Is used to reduce the sudden arrhythmic

death following myocardial infarction death following myocardial infarction

o Metoprolol Metoprolol

Selective Selective ββ11 blocker , used in blocker , used in asthmatic patients . Reduce the rate asthmatic patients . Reduce the rate of mortality due to post infarct of mortality due to post infarct arrhythmias.arrhythmias.

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• EsmololEsmolol• Is a short acting Is a short acting ββ1 blocking drug.1 blocking drug.• Used mainly for intraoperative Used mainly for intraoperative

acute arrhythmiasacute arrhythmias

Class 111:KClass 111:K++ channel channel blockersblockers

• Prolong the action potential Prolong the action potential duration & refractory period .duration & refractory period .

• Prolong phase 3 . Prolong phase 3 .

Drugs of class 111Drugs of class 111

• SotalolSotalol• AmiodaroneAmiodarone• IbutilideIbutilide

SotalolSotalol

• Nonselective Nonselective ββ- adrenergic receptor - adrenergic receptor blocker .blocker .

• Is used for the treatment of :Is used for the treatment of :1- Life- threatening ventricular arrhythmias.1- Life- threatening ventricular arrhythmias. 2-To maintain sinus rhythm in patients 2-To maintain sinus rhythm in patients with atrial fibrillation.with atrial fibrillation.3- For treatment of supra & ventricular 3- For treatment of supra & ventricular arrhythmias in pediatric age group. arrhythmias in pediatric age group.

• May induce torsade de pointesMay induce torsade de pointes

Ibutilide Ibutilide

• Given by a rapid I.V. infusion Given by a rapid I.V. infusion

• Used for the acute conversion of Used for the acute conversion of atrial flutter or atrial fibrillation to atrial flutter or atrial fibrillation to normal sinus rhythm.normal sinus rhythm.

• QT interval prolongation , so it QT interval prolongation , so it precipitates torsade de pointes.precipitates torsade de pointes.

AmiodaroneAmiodarone

• A) cardiac effectsA) cardiac effects• Has a broad actions :Has a broad actions :• Sodium channel blocking Sodium channel blocking • Potassium channel blockingPotassium channel blocking• Calcium channel blocking Calcium channel blocking • β- adrenoceptor blocking β- adrenoceptor blocking

Amiodarone(cont.)Amiodarone(cont.)

• B) Extracardiac effect B) Extracardiac effect

Peripheral vasodilataionPeripheral vasodilataion

PharmacokineticsPharmacokinetics

• Given orally Given orally • Slow onset of actionSlow onset of action• Long half-life(60 days ).Long half-life(60 days ). • Concentrated in many tissues.Concentrated in many tissues.• Eliminated by liver mostly as active Eliminated by liver mostly as active

metabolites.metabolites.

Clinical usesClinical uses

• Recurrent ventricular arrhythmias Recurrent ventricular arrhythmias resistant to other drugs.resistant to other drugs.

• In maintaining sinus rhythm in In maintaining sinus rhythm in patients with atrial fibrillation.patients with atrial fibrillation.

Adverse effectsAdverse effects

• Gray- blue skin discoloration Gray- blue skin discoloration • Corneal microdeposits Corneal microdeposits corneal corneal

opacity ,optic neuritis, blindnessopacity ,optic neuritis, blindness• pulmonary fibrosispulmonary fibrosis

Adverse effects (cont.)Adverse effects (cont.)

• Hypo or hyperthyroidismHypo or hyperthyroidism• Gastrointestinal upsetGastrointestinal upset• Hepatic toxicityHepatic toxicity

• ArrhythmiasArrhythmias• HypotensionHypotension

Class 1V: Calcium channel Class 1V: Calcium channel blockersblockers

Verapamil, Diltiazem Verapamil, Diltiazem • Their main site of action is A.V.N & Their main site of action is A.V.N &

S.A.N( slow conduction & prolong S.A.N( slow conduction & prolong effective refractory period ).effective refractory period ).

Class 1V (cont.)Class 1V (cont.)

• They are used in treatment of They are used in treatment of atrial flutter & fibrillation.atrial flutter & fibrillation.

• They are the second drugs of They are the second drugs of choice for the treatment of choice for the treatment of paroxysmal supra-ventricular paroxysmal supra-ventricular tachycardia tachycardia

Miscellaneous DrugsMiscellaneous Drugs

• AdenosineAdenosine• Binds to specific adenosine receptors Binds to specific adenosine receptors

( A( A11- purinergic receptors)- purinergic receptors)

• decreasing SA & AV nodal automaticity , decreasing SA & AV nodal automaticity , conduction velocity & prolong effective conduction velocity & prolong effective refractory period refractory period

Pharmacokinetics & UsesPharmacokinetics & Uses

• Very rapid onset of action .Very rapid onset of action .• Short half- life (seconds)Short half- life (seconds)• Given as a Given as a rapidrapid I.V. bolus injection I.V. bolus injection• First choice for the treatment of First choice for the treatment of

paroxysmal supraventricular paroxysmal supraventricular tachycardiatachycardia

Adverse effectsAdverse effects

• BronchospasmBronchospasm• Shortness of breathShortness of breath• Chest pain or burningChest pain or burning• FlushingFlushing• Hypotension.Hypotension.

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• Less effective in the presence of Less effective in the presence of adenosine receptors blockers such adenosine receptors blockers such as theophylline or caffeineas theophylline or caffeine

DigoxinDigoxin

• Treatment of atrial flutter and Treatment of atrial flutter and fibrillation , but not return the atrial fibrillation , but not return the atrial rhythm back to normal sinus rhythm back to normal sinus rhythmrhythm