Dr.U.P.RathnakarMD.DIH.PGDHM 1

Antiarrhythmic

Drugs

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AP of Pacemaker & Non-pace maker cells

How do antiarrhythmics work?

• Tachyarrhythmias mediated by changes in the cardiac action potential

• Drugs that alter the action potential alter cardiac arrhythmias [By altering ionic fluxes]

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How do antiarrhythmics work?Effect AP

• Change the shape of the cardiac AP.

1. Conduction velocity [CV].

2. Refractory period [RP]

3. Automaticity [AM]

• Antiarrhythmic drugs do this by altering the channels that control the flow of ions across the cardiac cell membrane.

Ca or Na

K

B Blocker

Ca or Na

AntiarrhythmicsClassification [Singh-Vaughn-Williams]

Sodium-channel-blockers

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Beta-blockersPot.channel blockers

•↓ •↑•↓

Calcium channel blockers

•↓• ↑• ↓

•↓•↑•↓

•↓ •↑•↓

Conduction Velocity

Refractory Period

Automaticity

AntiarrhythmicsClassification [Singh-Vaughn-Williams]

Sodium-channel-blockers

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Beta-blockers

• Propranolol

Pot.channel blockers

• Amiodarone

Calcium channel blockers

• Verapamil• Diltiazem

Miscellaneous• Adenosine• Magnesium • Digitalis • Atropine

Procainamide

Sotalol

Na+ Channel blockers Class 1A.Eg. Procainamide

.CV↓RP↑

.Atria & Ventricles

.Oral & i.v.

PK:Acetylation

Uses:AF, Reentrant tachy,VT

.ADEs:

Anticholinergic

SLE

Proarrhythmic- Torse-De

Pointes

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Class 1BEg.LignocaineNa+ ChannelNo action at low HRUser dependentAPD[RP] ↓Only ventriclesi.v[bolus-infusion]Use: Vent.arrhythmiasADEs: CNSProarrhythmic-rare

Class 1CEg. Porpaafenone

↓↓↓ Conduction-V.potent

Oral

-ve inotropic

Uses: atrial & Vent.arrhythmias

ADEs: Visual disturbances

GIT effects

Reserve drug

Na+ Channel blockers Class 1A

Procainamide

Diisopyramide

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Class 1B

Lignocaine

Mexiletine[O]

Class 1C

Propafenone

[Also B-blocker]

Reserve drug

Class II-BetablockersEg.atenolol,propranolol

• Mild, blunt arrhythmogenic effect• SA Node-Phase 4 is blunted-reduces automaticity• AV Node-slows conduction• Protective-Prevents reentrant tachycardias• Uses:• Effective in arrhythmias where SA & AV nodes are involved• AF & AFL-Reduces ventricular response• Not effective in treating ventricular arrhythmias, but effectively

protects.

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Class III-K+ channel blockersEg.Amiodarone

• K+ channel blocker[CL III], Na channel blocker[CL I], betablockade[CL II], Ca channel blockade[CL IV]

• Prolongs APD-ERP• Large volume of dist.-slow action, loading dose• Immediate antiarrhythmic effects are due to

non CL III effects• Oral and i.v. administration

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Class III-K+ channel blockersEg.Amiodarone

• Uses:• Broad spectrum antiarrhythmic• Most effective in recurrent ventricular fibrillation• AF, reentrant tachycardias-AV nodal, WPW

syndrome• Others-Sotalol. Ibutilide, dobutilide

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Class III-K+ channel blockersEg.Amiodarone

• ADEs: 15% to 50% of pts.• Cumulative drug• GIT-nausea, vomiting,esophageal reflux• Reversible elevation of liver transaminases• Pneumonitis, pulmonary fibrosis• Iodine containing compound-prevents peripheral

conversion of T4 to T3• Hypothyroidism or hyperthyroidism• Cutaneous, neurological, ocular symptoms• ADEs:Torsede-de-pointes[Not common] 43

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Class IV-Ca++ channel blockersVerapamil & Diltiazem

• Low BA

• Inhibit Ca ++ dependent depolarization in SA & AV node

• ↓Automaticity, ↓ conduction and RP• Uses:• Control Vent.response in atrial

tachyarrhythmias• AV nodal and bypass reentrant arrhythmias

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Unclassified antiarrhythmics

• Digoxin-In AF to lower vent.response• Adenosine-Short acting, depresses AV

node, used in reentrant tachyarrhythmi s [Adenosine R→K Channels→Hyperpolarization

• Magnesium-Torsades-de-pointes, digitalis toxicity

• Atropine-H.block• Isoprenaline-H.block, Torsede de pointes• Others-Azimilide, Dronedarone, tedisamil,

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Principles in clinical use of antiarrhythmics

• Narrow margin of safety• Proarrhythmics• Non-pharmacological measures [pacing,

cardioversion]

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Principle-1

• Identify and remove precipitating factors

1. Electrolyte disturbances

2. Hypoxia

3. Ischemia

4. Digoxin

5. Other drugs used for non cardiac conditions[Erythromycin, pentamidine, antipsychotics]

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Principle-2

• Establish goals

1. Some should not be treated

Eg. Asymptomatic ventricular ectopics

2. Symptoms- Sensation of irregular beats, Syncope, breathlessness, cardiac failure

3. Choosing therapeutic approaches-• Restoring sinus rhythm-• Reducing ventricular rate 49

Principle-3

• Minimize risks

1. Antiarrhythmics can cause arrhythmia

2. Monitor plasma concentraion

3. Pt.specific contra-indications Eg. Pulmonary disease & Amiodarone

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Principle-4

• Heart is a moving target!

1. Cardiac electrophysiology varies in a highly dynamic fashion

Eg.autonomic tone, ischemia, cardiac stretch, electrolyte variations

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Type of arrhythmia Acute Chronic(PSVT)

AVN reentryAdenosine, B-blockers, Ca channel blockers

B-blockers, Ca channel blockers

PSVT- AV reentry Same as above K or Na channel blockers

Atrial fibrillationAtrial flutter

1. Control ventricular response: AV node block2. Restore sinus rhythm: DC cardioversion

1. AV nodal block2. Maintain normal rhythm: K+ channel block, Na+ channel block

Ventricular tachycardiaVF

Lidocaine, AmiodaroneProcainamide, DC cardioversion, Adenosine

ICDAmiodarone, K+ channel block, Na+ channel block

Torsede de pointes Mg, Isoprenaline Beta blockers, pacing

A-V block Atropine, Isoprenaline