Antiarrhythmic Drugs

30-1-14 [2nd class] Dr.U.P.Rathnakar www.scribd.com

23

MD.DIH.PGDHM

Ito Pot.
channels
Ca 3 0 4 4 AP in pacemaker tissue K Na Ca & K+

IK

Pot.

channels

AP in non-pacemaker tissue

22

Pathogenesis of arrhythmias
Abnormalities of spontaneous automaticity Abnormalities of impulse generation Abnormalities of triggered automaticity

Impulse block Abnormalities of impulse propagation Re-entry phenomenon Anatomically defined Functionally defined

AVN

AV

21

Pathogenesis of arrhythmia
[Mechanisms of arrhythmias]

Triggered automaticity
[Abnormality of impulse generation]

Re-entry phenomenon [Circus movement]

[Abnormality of impulse conduction]

20

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]
19

 Change the shape of the cardiac AP.

How do antiarrhythmics work? Effect AP

Ca or Na

B Blocker

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.
18

Antiarrhythmics Classification [Singh-Vaughn-Williams]

Sodium-channelBeta-blockers blockers
Pot.channel blockers Calcium channel blockers

Conduction Velocity

Refractory Period

Automaticity

17

How do antiarrhythmics work? Effect on AP

CV decreased Increase RP[APD]

Decrease RP[APD]

16

Antiarrhythmics Classification [Singh-Vaughan-Williams]

Sodium-channelblockers [Cl ass I]
Procainamide

Beta-blockers [Class II]

Calcium channel Pot.channel blockers[Class III] blockers [Class IV]

Propranolol Amiodarone Verapamil Diltiazem Sotalol

Miscellaneous Adenosine Magnesium Digitalis Atropine

15

Na+ Channel blockers

Class 1A[Mod]
.Eg. Procainamide .CVRP .Atria & Ventricles .Oral & i.v. PK:Acetylation Uses:AF, Reentrant tachy,VT .ADEs: Anticholinergic SLE Proarrhythmic- Torse-De Pointes
Na+ * K+

Class 1B[Weak]
Eg.Lignocaine Na+ Channel No action at low HR [User dependent] APD[RP] Only ventricles i.v[bolus-infusion] Use: Vent.arrhythmias ADEs: CNS Proarrhythmic-rare

Class 1C[Profound]
Eg. Porpafenone Conduction- profound Oral -ve inotropic Uses: atrial & Vent.arrhythmias ADEs: Visual disturbances GIT effects Reserve drug

Na+ only

Na+ & some K+ 14

Na+ Channel blockers

Class 1A Class 1B Class 1C

Procainamide Lignocaine Diisopyramide Mexiletine[O]

Propafenone [Also B-blocker] Flecanide

11

Class II-Betablockers
Eg.atenolol,propranolol, esmolol
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.

12

Class III-K+ channel blockers

Eg.Amiodarone, Dronedarone, Dofetilide, Ibutilide

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
11

Class III-K+ channel blockers

Eg.Amiodarone

Uses: Broad spectrum antiarrhythmic Most effective in recurrent ventricular fibrillation AF, reentrant tachycardias-AV nodal, WPW syndrome Others-Sotalol. Ibutilide, dobutilide

10

Class III-K+ channel blockers

Eg.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]

Class IV-Ca++ channel blockers

Verapamil & 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
8

Unclassified antiarrhythmics
Digoxin-In AF to lower vent.response Adenosine-Short acting, depresses AV node, used in reentrant tachyarrhythmi s [Adenosine RK ChannelsHyperpolarization Magnesium-Torsades-de-pointes, digitalis toxicity Atropine-H.block Isoprenaline-H.block, Torsede de pointes
7

Principles in clinical use of antiarrhythmics

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

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]
5

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

Principle-3
Minimize risks 1. Antiarrhythmics can cause arrhythmia 2. Monitor plasma concentraion 3. Pt.specific contra-indications Eg. Pulmonary disease & Amiodarone

Principle-4
Heart is a moving target! 1. Cardiac electrophysiology varies in a highly dynamic fashion Eg.autonomic tone, ischemia, cardiac stretch, electrolyte variations

Type of arrhythmia Paroxysmal supraventricular tachycardias (PSVT) Atrial fibrillation Atrial flutter

Drugs used
Adenosine Verapamil Digoxin
Esmolol Verapamil Amiodarone Esmolol Verapamil Digoxin Amiodarone Lignocaine Procainamide Amiodarone Lignocaine Amiodarone Atropine Isoprenaline

Ventricular tachycardia

Ventricular fibrillation
A-V block

23