Anti arrhythmic drugs

Dr. S. Parthasarathy MD., DA., DNB, MD (Acu),

Dip. Diab.DCA, Dip. Software statistics, Phd (physio)

Mahatma Gandhi Medical college and research institute , puducherry , India

•What is normal ??

Electrophysiology - resting potential

• A transmembrane electrical gradient (potential) is maintained, with the interior of the cell negative with respect to outside the cell

• Caused by unequal distribution of ions inside vs. outside cell Na+ Ca +– Na+ higher outside– Ca+ much higher– K+ higher inside

• Maintenance by ion selective channels, active pumps and exchangers

K +

Diastole

Na

Phase 2 - plateau phase

sustained by the balance between the inward movement of Ca+

and outward movement of K +

Has a long duration compared to other nerve and muscle tissue

Normally blocks any premature stimulator signals (other muscle

tissue can accept additional stimulation and increase

contractility in a summation effect)

Corresponds to ST segment of the ECG.

Phase 3 – repolarization

K+ channels remain open,

Allows K+ to build up outside the cell, causing the

cell to repolarize

K + channels finally close when membrane potential

reaches certain level

Corresponds to T wave on the ECG

Reminder

Vaughan Williams classification of drugs • Class I --- A – quinidine ,morizicine,

procainamide,disopyramide B- lignocaine,mexilitine tocainide,

phenytoin C-flecainide , propofenone • Class II – beta blockers • Class III – sotalol, Bretylium, Amiodarone,

Acecainide Dofetilide, Ibutilide, Azimilide• Class IV – Verapamil, Diltiazem,Bepridil• Miscellaneous :digoxin, adenosine

Four classes of drugs

Some Block

Potassium Channels

Go into each

BAC

ON PACEMAKER POTENTIAL

Class I A

• Phase 0- decrease velocity and amplitude • APD and ERP increased • Quinidine decreases automaticity in atrial and

ventricular tissue and in the His-Purkinje and pacemaker fibers

• SA node - ? Action due to anticholinergic effects

Class I A

• Quinidine 200 mg six hourly tablets • Digoxin or verapamil – add to decrease

ventricular response • But digoxin toxicity ??

• Diarhoea, thrombocytopenia ,hypotension, arrythmias !!

Indications of quinidine

• conversion of atrial fibrillation, atrial flutter,

• PSVT,

• maintenance of sinus rhythm after conversion.

• In addition, it suppresses ventricular ectopy,

• tachycardia, and fibrillation.

Procainamide

• 1 gm iv bolus – 1 mg /min.• Atrial and ventricular arrhythmias

• Neg.inotropy, CHF?? Puts a hold

• NAPA (N acetyl procainamide)– class III actions

Difficult private question

Disopyramide,procainamide and quinidine

Class I B

Lignocaine

• they shorten APD and ERP and increase the ERP-to-APD ratio in the Purkinje fibers,

• NO effect on the refractory periods in sinus node, atrium, and AV node

• 1 mg/kg – 1 mg/minute infusion – no tapering • Effect on SVT ?? • PVC s !!

Phenytoin

• I B effects – centrally mediated sympatholysis

• Prolonged QT interval + atrial and ventricular arrhythmias

• 1 gm IV bolus + 50 mg/ min.

• Other side effects ??

• Difficult private question

• Marks ??

• Pick low marks • Phenytoin, lignocaine and mexilitine

Class I C

Class I C - flecainide, propofenone • slow AV node, His-Purkinje and ventricular

conduction--ERP unchanged

• Used for ventricular arrhythmias and also WPW

• drugs suppress automaticity of the SA node,• Negative inotropy, arrest, more mortality

Class I –Na+channel blockers

• Class I a : Used most frequently for conversion of atrial flutter/fibrillation and maintenance of sinus rhythm.

• Class I b : Used for ventricular arrhythmias, especially those associated with myocardial infarction/ischemia but not for prophylaxis.

• Class I c : Used for atrial flutter/fibrillation in patients with structurally normal hearts.

• Difficult private question

• Pick low marks

• Final exam proficiency ??• Flecainide , encainide , propofenone

Class II • β–adrenergic blockers– Based on two major actions

1) blockade of myocardial β–adrenergic receptors

2) Direct membrane-stabilizing effects related to Na+ channel blockade

Sinus node !! Rate of spontaneous depolarization

decreased

Beta blockers • β-Adrenergic antagonists are effective for the treatment

of cardiac dysrhythmias related to enhanced activity of

the sympathetic nervous system (perioperative stress,

thyrotoxicosis, pheo)

• Ischemia

• Acebutolol, propranolol, and metoprolol are approved

for the prevention of sudden death following myocardial

infarction.

Class III – amiodarone

Amiodarone

• Blocks potassium channels ,Prolongs repolarization Vasodilator -- Even coronary

SVT and VT Рboth å With intravenous therapy, an initial loading dose of

150 mg is given over 10 minutes. • continuous infusion of 1 mg/min for 6 hours

followed by 0.5 mg/min • 5% dextrose solution• Thyroid – lipophilic – eye – heart block-new VF

Amiodarone - Pulmonary fibrosis

Bretylium

• Class III action , blocks norad release • Chemical sympathectomy • Loading dose 5 mg / kg – • Unresponsive Ventricular arrhythmias • Replaced by amiodarone • Direct( Increased action)and indirect( less

action) vasopressors • Bupi induced arrhythmias

sotalol

• PO: 40–80 mg.( class III + beta blocking)• Ventricular arrhythmias • Ibutilide has been approved for acute termination of

atrial fibrillation or flutter• Intravenous dosage is • 1 mg over 10 minutes

• No action on AV node

Class III

• Dofetilide is approved for acute conversion of atrial

fibrillation and atrial flutter to sinus rhythm, and for

prevention of recurrence of atrial fibrillation.

• It is a very potent K channel blocker

• Problem -- QT prolongation and torsades de pointes

• Class III • IS BAD

• I butilide• S otalol• B retylium• A miodarone• D ofetilide

CALCIUM CHANNEL BLOCKERS

• VERAPAMIL • NIFIDEPINE • DILTIAZEM

• CALCIUM CHANNEL BLOCKERS • VERY NICE DRUGS

Verapamil

• Verapamil inhibit the flux of calcium ions across the

slow channels of smooth muscle and cardiac cells.

• decreased rate of spontaneous phase 4 depolarization.

• Verapamil has a substantial depressant effect on the

atrioventricular node and a negative chronotropic

effect on the sinoatrial node.

Verapamil

• Supraventricular tachydysrhythmias (action on

atrioventricular node)

• Vasospastic angina pectoris (mild vasodilating effects)

• Essential hypertension (mild vasodilating effects)

• Hypertrophic cardiomyopathy

• 40 – 80 mg tds or 100 mic gm / kg IV

• SA node depression is not with dilzem

• Cautious use with digoxin

Adenosine • Adenosine is an endogenous nucleotide natural to all

cells of the body

• In pharmacologic doses, it slows conduction through

the AV node

• Efficacious as acute IV therapy for patients with

paroxysmal supraventricular tachycardia in both

reentry and accessory pathway (Wolff-Parkinson-

White) dysrhythmias.

Adenosine • SVT – re entry or accessory tract

• 6mg IV bolus - --then 12 mg – 92 % conversion

• AF ?? Use

• Blocks and sick sinus – dangerous

• Caffeine – decreases levels

• Wheezing, brady- even asystole • intrathecal adenosine might be effective in the

treatment of acute and chronic pain

Pearls

Start everything but amiodarone in house.

Drugs work best when the EF is high.Drugs have most proarrhythmia when EF is low. Only amiodarone, sotalol, and dofetilide are known

safe in low EF patients.

Pearls

Use amiodarone, quinidine, mexiletine, moricizine, ibutilide, or lidocaine in renal failure.

• Amiodarone’s risk of torsades is poorly related to QT prolongation.

• Classes Ia, Ic, II, IV are negatively inotropic.• Use AV blockers with class Ic drugs for PAF.• Monitor QRS duration with class Ic drugs.

• If you don’t know what arrhythmia is that ??

• Better use amiodarone

In anaesthesia

• Adenosine • Verapamil • Lignocaine • Amiodarone • Beta blockers• Digoxin

• ACLS specialists • Not going into the

details of perioperative arrhythmias

• Beta blockers propofenone • Verapamil

• Digoxin Quinidine• Verapamil amiodarone • Adenosine

• Lignocaine

•Why should we read this topic ??

• The first recorded death during anesthesia, that of

Hannah Greener in 1848, was most likely because of

ventricular fibrillation (VF) resulting from the

“sensitizing” action of chloroform

Thank you all