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 – both √ 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