Antiarrhythmic DrugsAntiarrhythmic Drugs

• Normal heart rate Normal heart rate • Action potentialAction potential• ECGECG

Factors precipitate Factors precipitate arrhythmiasarrhythmias

• May includes :May includes :• Ischemia, hypoxia, electrolytes Ischemia, hypoxia, electrolytes

disturbance, excessive disturbance, excessive catecholamines exposure , catecholamines exposure , drug toxicity.drug toxicity.

Mechanisms of Mechanisms of arrhythmiasarrhythmias

1- 1- Disturbances in impulse formation.Disturbances in impulse formation.

• Vagal stimulation or Vagal stimulation or ββ- receptor blocking - receptor blocking drugs slow normal pacemaker .drugs slow normal pacemaker .

• Acceleration of pacemaker by Acceleration of pacemaker by hypokalemia or hypokalemia or ββ-- adrenoceptor adrenoceptor stimulants.stimulants.

• Development of ectopic pacemakersDevelopment of ectopic pacemakers.. - -• --

2- Disturbances in 2- Disturbances in impulse conductionimpulse conduction

• May result from block ( nodal block or May result from block ( nodal block or bundle branch block .bundle branch block .

• Reentry : Reentry : • circus movementcircus movement In which one impulse reenters and In which one impulse reenters and

excites areas of the heart more excites areas of the heart more than than ones.ones.

• Some forms of reentry are Some forms of reentry are anatomical in shape as in Wolff-anatomical in shape as in Wolff-Parkinson Parkinson ––White syndrome. White syndrome.

Antiarrhythmic DrugsAntiarrhythmic Drugs

• Class 1Class 1 : Na+ channel blockers : Na+ channel blockers• Local anaesthetic effectLocal anaesthetic effect• -ve inotropic action-ve inotropic action• Class 1( A Class 1( A ): prolongs duration of action ): prolongs duration of action

potential & refractory period.potential & refractory period.• Have K+ channel blocking effectHave K+ channel blocking effect• Antimuscarinic & hypotensive effects.Antimuscarinic & hypotensive effects.

. . Class1(B)Class1(B):Shorten the duration of :Shorten the duration of action potential & refractory period action potential & refractory period

– Class1(C)Class1(C) : No effect on the duration : No effect on the duration of action or refractory period.of action or refractory period.

• Class 11Class 11 : : ββ-adrenoceptor blockers.-adrenoceptor blockers.• Class 11Class 111: K+ channel blockers,1: K+ channel blockers,• Prolong duration of action potential Prolong duration of action potential

and refractory period.and refractory period.

• Class1VClass1V : Ca++ channel blockers. : Ca++ channel blockers.• Miscellaneous drugs.Miscellaneous drugs.

Class 1(A) Class 1(A) Quinidine:Quinidine:

• Cinchona plantCinchona plant• Block open & inactivated sodium Block open & inactivated sodium

channelchannel• Block potassium channelBlock potassium channel• -ve inotropic effect-ve inotropic effect• Antimuscarinic effect Antimuscarinic effect duration of action potential & refractory duration of action potential & refractory

periods of atrium & ventricles.periods of atrium & ventricles.• HypotensiveHypotensive

ECG changesECG changes

• Prolong Q-T intervalProlong Q-T interval• Widening QRS complexWidening QRS complex

PhrmacokineticsPhrmacokinetics

• Well absorbed orallyWell absorbed orally• Highly bound to plasma proteinsHighly bound to plasma proteins• Metabolized in liver ( active metabolite)Metabolized in liver ( active metabolite)• 20% excreted unchanged in urine20% excreted unchanged in urine• Usually given as slow release Usually given as slow release

formulationformulation• I.M. painful, I.V(marked hypotension) I.M. painful, I.V(marked hypotension)

Clinical usesClinical uses

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

• Used in treatment of ventricular Used in treatment of ventricular arrhythmia.arrhythmia.

Adverse effects Adverse effects

• 1- Cardiac effects 1- Cardiac effects • A) Due to antimuscarinic effect ,in A.F.or A) Due to antimuscarinic effect ,in A.F.or

A.F. may precipitate ventricular A.F. may precipitate ventricular tachycardiatachycardia

• B) SyncopeB) Syncope• C)Torsade de pointesC)Torsade de pointes• D) Cardiac stand still (asystole) in D) Cardiac stand still (asystole) in

patients with sick sinus syndrome .patients with sick sinus syndrome .

Extracardiac adverse Extracardiac adverse effectseffects

• HypotensionHypotension

• Cinchonism (headache, Cinchonism (headache, dizziness,tinnitus,deafness )dizziness,tinnitus,deafness )

• Hypersensitivity reactions Hypersensitivity reactions (hepatitis,thrombocytopenia)(hepatitis,thrombocytopenia)

• GIT, GIT, diarrheadiarrhea,nausea,vomiting,nausea,vomiting

Drug interactionsDrug interactions

• Quinidine increases the plasma Quinidine increases the plasma level of digoxin by :level of digoxin by :

a) displacement from tissue a) displacement from tissue binding sitesbinding sites

b) decreasing digoxin renal b) decreasing digoxin renal clearanceclearance

ProcainamideProcainamide

• As quinidine but :As quinidine but :• Less hypotensive Less hypotensive • Less antimuscarinic Less antimuscarinic • Less cardiotoxic Less cardiotoxic • Can be given safely by I.M. or I.V. Can be given safely by I.M. or I.V. • Metabolized in liver and give active Metabolized in liver and give active

metabolite which has a class 111 metabolite which has a class 111 activity .activity .

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• Eliminated through kidney .Eliminated through kidney .• More effective in ventricular arrhythmias More effective in ventricular arrhythmias

, it is the , it is the second drug of choice after second drug of choice after lidocaine in treament of ventricular lidocaine in treament of ventricular arrhythmia follow acute M.I.arrhythmia follow acute M.I.

• Effective in A.F. or A.F. due to Wolff Effective in A.F. or A.F. due to Wolff Parkinson White syndromeParkinson White syndrome

Adverse effectsAdverse effects

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

• GIT : Nausea , diarrheaGIT : Nausea , diarrhea• Torsade de pointesTorsade de pointes• HypotensionHypotension

Class 1(B)Class 1(B)

• LidocaineLidocaine• Shorten the duration of A.P.& R.P.Shorten the duration of A.P.& R.P.• Effective in ventricular Effective in ventricular

arrhythmias.arrhythmias.

PharmacokineticsPharmacokinetics

• Well absorbed after oral Well absorbed after oral administration . Only 3% reach administration . Only 3% reach general circulation.general circulation.

• Given only by I.V. routeGiven only by I.V. route• Excreted via kidney .Excreted via kidney .• Half-life 2hrs.Half-life 2hrs.

Therapeutic usesTherapeutic uses

• First drug of choice in treatment of First drug of choice in treatment of ventricular arrhythmias due toventricular arrhythmias due to

• Acute myocardial infarctionAcute myocardial infarction• Digitalis toxicityDigitalis toxicity• AnaesthesiaAnaesthesia• Open heart surgeryOpen heart surgery

Adverse effectsAdverse effects

• Neurological effects :Neurological effects :(contraindicated in epileptic patients ).(contraindicated in epileptic patients ).

• Arrhythmias uncommon Arrhythmias uncommon

• Hypotension Hypotension

MexiletineMexiletine

• Effective orallyEffective orally• Half-life (8-20hrs ).Half-life (8-20hrs ).• Used in chronic treatment of Used in chronic treatment of

ventricular arrhythmias.ventricular arrhythmias.• Effective in relieving chronic pain Effective in relieving chronic pain

due to diabetic neuropathy& nerve due to diabetic neuropathy& nerve injury.injury.

Adverse effectsAdverse effects

• Neurologic side effectsNeurologic side effects

Class1(c)Class1(c)

• FlecainideFlecainideNo effect on the duration of A.P.& No effect on the duration of A.P.&

R.P.R.P.

• Proarrhythmic Proarrhythmic

• Approved for refractory ventricular Approved for refractory ventricular arrhythmias.arrhythmias.

PropafenonePropafenone

• Has a weak Has a weak ββ-blocking effect.-blocking effect.• Used to maintain sinus rhythm in Used to maintain sinus rhythm in

patients with supraventricular patients with supraventricular arrhythmias including AF.arrhythmias including AF.

• Adverse effectsAdverse effects : :Metallic taste, constipation .Metallic taste, constipation .

Class 11Class 11

Beta-Adrenoceptor-Blocking Drugs.Beta-Adrenoceptor-Blocking Drugs.Effective in atrial & ventricular Effective in atrial & ventricular

arrhythmias that associated with arrhythmias that associated with Increase in sympathetic activity .Increase in sympathetic activity .Reduce the incidence of sudden Reduce the incidence of sudden

arrhythmic death after myocardial arrhythmic death after myocardial infarction.infarction.

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• PropranololPropranolol

• Metoprolol ( Metoprolol ( ββ11 selective) selective)

• EsmololEsmolol

Very short acting used for Very short acting used for intraoperative & acute arrhythmiasintraoperative & acute arrhythmias

Class 111Class 111

• Potassium channel blockersPotassium channel blockers• ( Drugs that Prolong duration of ( Drugs that Prolong duration of

action potential & refractory period action potential & refractory period ).).

SotalolSotalol

• Nonselective Nonselective ββ- adrenergic receptor - adrenergic receptor antagonist .antagonist .

• Is used for the treatment of :Is used for the treatment of : Life- threatening ventricular Life- threatening ventricular

arrhythmias.arrhythmias. To maintain sinus rhythm in To maintain sinus rhythm in

patients with atrial fibrillation.patients with atrial fibrillation. For treatment of supra & For treatment of supra &

ventricular arrhythmias in ventricular arrhythmias in pediatric pediatric age group. age group.

Ibutilide Ibutilide

• Given by a rapid I.V. infusion Given by a rapid I.V. infusion • excreted mainly as metabolites by excreted mainly as metabolites by

kidney.kidney.• 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.

• Q-T interval prolongation , so it Q-T interval prolongation , so it precipitates torsade de pointes.precipitates torsade de pointes.

AmiodaroneAmiodarone

• A)A) cardiac effectscardiac effects

Sodium channel blocking Sodium channel blocking

Potassium channel blockingPotassium channel blocking

Calcium channel blocking Calcium channel blocking

β- adrenoceptor blocking β- adrenoceptor blocking

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• B) Extracardiac effect B) Extracardiac effect

Peripheral vasodilationPeripheral vasodilation

PharmacokineticsPharmacokinetics

• Given orally Given orally • Slow onset of actionSlow onset of action• Long half-life(13-103 hrs ).Long half-life(13-103 hrs ).• Cumulative drug Cumulative drug • Is highly lipophilic , is concentrated Is highly lipophilic , is concentrated

in many tissues.in many tissues.• Eliminated by liver mostly as active Eliminated by liver mostly as active

metabolites.metabolites.

Clinical usesClinical uses

• Recurrent & refractory ventricular Recurrent & refractory ventricular & supraventricular arrhythmias .& supraventricular arrhythmias .

• Arrhythmias associated with Wolff Arrhythmias associated with Wolff Parkinson syndrome.Parkinson syndrome.

• In maintaining sinus rhythm in In maintaining sinus rhythm in patients with AF.patients with AF.

Adverse effectsAdverse effects

• Gray- blue skin discoloration & Gray- blue skin discoloration & photodermatitis .photodermatitis .

• Corneal microdeposits Corneal microdeposits corneal corneal opacity ,optic neuritis, blindness opacity ,optic neuritis, blindness

• pulmonary fibrosispulmonary fibrosis

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• hypo or hyperthyroidismhypo or hyperthyroidism• Nausea & constipationNausea & constipation• Hepatic impairmentHepatic impairment• neurological effects neurological effects • A-V block & bradycardiaA-V block & bradycardia• HypotensionHypotension

Drug interactionsDrug interactions

• Oral anticoagulant Oral anticoagulant bleedingbleeding• DigoxinDigoxindigoxin toxicitydigoxin toxicity• β- blockers β- blockers additive effectadditive effect

Class 1VClass 1V

• Calcium channel blockersCalcium channel blockers• e.g. Verapamil, Diltiazeme.g. Verapamil, Diltiazem• Their main site of action is A.V.N & Their main site of action is A.V.N &

S.A.N.S.A.N.• Effective only in atrial arrhythmias Effective only in atrial arrhythmias

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• Second drugs of choice for the Second drugs of choice for the treatment of paroxysmal treatment of paroxysmal supraventricular tachycardia supraventricular tachycardia

• Not effective in Wolff Parkinson Not effective in Wolff Parkinson White syndrome.White syndrome.

Adverse effectsAdverse effects

• -Ve inotropic effect causes H.F.-Ve inotropic effect causes H.F.• A-V blockA-V block

• Constipation , headache , Constipation , headache , peripheral edemaperipheral edema

Miscellenous drugsMiscellenous drugs

• AdenosineAdenosineBinds to specific G protein Binds to specific G protein ––

coupled adenosine receptors coupled adenosine receptors

(A(A11&A&A22))opening K+ opening K+ channelchannelhyperpolarization.hyperpolarization.

• influx of calciuminflux of calcium

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

For the acute termination of For the acute termination of re-entrant supraventricular re-entrant supraventricular tachycardia ( paroxysmal tachycardia ( paroxysmal attack) attack) First choice.First choice.

Adverse effectsAdverse effects

• BronchospasmBronchospasm• Chest painChest pain• Shortness of breathShortness of breath• FlushingFlushing• A-V blockA-V block• HypotensionHypotension

ContraindicationsContraindications

• Bronchial asthmaBronchial asthma• A-V blockA-V block

Drug interactionsDrug interactions

• Less effective with adenosine Less effective with adenosine receptor blockers ( Caffeine or receptor blockers ( Caffeine or theophylline theophylline

• More effective with uptake More effective with uptake inhibitors as dipyridamole inhibitors as dipyridamole

MagnesiumMagnesium

• Used in:Used in:• Digitalis induced arrhythmiasDigitalis induced arrhythmias• Torsade de pointesTorsade de pointes• Sinus tachycardiaSinus tachycardia

PotassiumPotassium

• Used in:Used in:• Digitalis induced arrhythmiasDigitalis induced arrhythmias