Antiarrythmic drugs

Antiarrhythmic drugs by Dr. Md. Saiduzzaman

1. Anti-arrhythmic Drugs and updates

2. Speaker: Dr. Md. Saiduzzaman MD Resident (Neurology), Mymensingh Medical College Hospital.

3. What is an Arrhythmia? The arrhythmias are altered cardiac rhythm caused by abnormalities in- impulse formation (abnormal automaticity) conduction in the myocardium (reentry), or combination of both. However, in the cardiology ward, arrhythmias present as a complex family of disorders that show a variety of symptoms.

4. Why should we treat arrhythmia? Arrhythmias can cause serious complications like- Heart failure. Sudden cardiac death Syncope. Stroke.

5. Factors that precipitate arrhythmia: − Cardiac ischemia, Structural heart disease, Hypoxia, Acidosis, alkalosis Electrolyte disturbances Excessive catecholamine exposure Exposure to toxic substances Unknown etiology

6. The heart cavity from which the arrhythmia originates gives the name to the arrhythmia 1. Supraventricular Ectopic (atrial or AV nodal) Multifocal Atrial Tachycardia(MAT) Atrial fibrillation and flutter 2 . Ventricular Ectopic ( Extrasystole or PVC) Tachycardia Ventricular fibrillation

7. ARRHYTHMIAS Sinus arrythmia Atrial arrhythmia Nodal arrhythmia ( junctional ) Ventricular arrhytmia SVT

8. +30 mV 0 mV -80 mV -90 mV OUTSIDE MEMBRANE INSIDE Na+ 4 3 2 1 K + C a ++ K + Atp K + Na+ K + Ca ++ Na+ K + Na+ Resting open Inactivated Phase zero depolarization Early repolarization Plateau phase Rapid Repolarization phase Phase 4 depolarization

9. Antiarrhythmic drugs

10. Vaughn william Classification:

11. Class I – blocker’s of fast Na + channels Subclass IA Cause moderate Phase 0 depression Prolong repolarization Increased duration of action potential Includes Quinidine – 1 st antiarrhythmic used, treat both atrial and ventricular arrhythmias, increases refractory period Procainamide - increases refractory period but side effects Disopyramide – extended duration of action, used only for treating ventricular arrhythmias

12. Quinidine -indications and MOA Indication: both VA and SVA Blocks activated Na + channel: ↓slope of phase 0 and 4 Inhibit K + current: ↑phase 3 Both above effects  ↑ Action potential  ↑ QT interval α -blocking  vasodilation reflex tachycardia Antimuscarinic effect

13. Quinidine -adverse effects Cardiac Adverse effects: torsade depoints ( ↑ QT interval) twisting of peak in ECG Proarrhythmogenic effects, AV block or asystole (toxic dose) Extracardiac Adverse effects: GIT: Diarrhoea,Nausea,Vomiting Cinchonism : headache, dizziness, confusion, tinnitus, deafness, blurring of vision Quinidine syncope because of VA ( ↑QT ); light headedness and fainting

14. Shortens depolarization. Decreased action potential duration Lidocaine (also acts as local anesthetic) – blocks Na + channels mostly in ventricular cells, also good for digitalis-associated arrhythmias. Mexiletine - oral lidocaine derivative, similar activity. Phenytoin – anticonvulsant that also works as antiarrhythmic similar to lidocaine . Subclass IB: Lidocaine , mexiletine , tocainide , phenytoin

15. Class IB- Lidocaine t 1/2 1-1.5 hr given by I.V loading dose followed by I.V infusion Block both activated & inactivated Na + channel ↓ The slope of phase 0 & 4 Main uses: Ventricular Arrhythmia following MI.

16. Dose : IV 75-200 mg flushing, then 2-4 mg/min for 24-30 hrs. Flushing dose is given to saturate hepatic enzymes. Dose reduction by half is required in conditions where hepatic blood flow is reduced. ( shock,beta-blocker,hepatic cirrhosis, severe heart failure)

17. Lidocaine adverse effects CNS: drowsiness, numbness, parathesia, slurred speeches, difficulty of swallowing, convulsions, nystagmus, tremor, Diplopia Heart: AV block ↓ contractility

18. Strong Phase 0 depression No effect of depolarization No effect on action potential duration Flecainide (initially developed as a local anesthetic) Potent blocker of Na + shorten AP Potent blocker of K + prolong AP Net result no change Slows conduction in all parts of heart, Also inhibits abnormal automaticity Proarrhytmogenic : reserved for life threatening SVA & VA in pts without myocardial structural abnormalities Subclass IC: flecainide , propafenone , moricizine

19. Class IC- Flecainide , Propafenone & Moricizine Propafenone Has some structural similarities to propranolol Weak β – blocker Also some Ca 2+ channel blockade Also slows conduction VA & SVA: its spectrum of action similar to that flecainide AE: metallic taste & constipation Moricizine Derivative of phenothiazine Mechanism of action similar to flecainide -VA Proarrhythmogenic

20. Class II – β –adrenergic blockers Based on two major actions blockade of myocardial β –adrenergic receptors  ↓ cAMP  ↓ both Na+ & Ca+ current 2) Direct membrane-stabilizing effects related to Na + channel blockade  ↓both automaticity & HR and suppression of abnormal pacemaker activity The AV node is particularly sensitive to β -blockers The PR interval is usually prolonged by β -blockers

21. Class II- β –adrenergic blockers Propranolol Slows SA node and ectopic pacemaker Can block arrhythmias induced by exercise or apprehension Other β –adrenergic blockers have similar therapeutic effect Metoprolol , Nadolol , Atenolol , Acebutolol , Pindolol , Sotalol , Timolol ; prophylactic in MI Esmolol (very short acting; I.V exclusively for acute surgical arrhythmia)

22. Class III – K + channel blockers Cause delay in repolarization and prolonged refractory period Includes: Amiodarone – markedly prolongs action potential by delaying K + efflux. Ibutilide – slows inward movement of Na + in addition to delaying K + influx. Bretylium – is an older drug that combines general sympathoplegic actions & a K + channel blocking effects in ischemic tissues. Dofetilide - is a newer K + channel blocker prolongs action potential by delaying K + efflux.

23. Class III- Amiodarone Structurally related to thyroid hormone. Effective in most types of arrhythmias & is most efficacious of all antiarrhythmic, because of toxicities, mainly used in arrhythmias that are resistant to other drugs. Blocks Na + , Ca +2 & K + channels and α -& β - receptors Marked prolongs the QT interval & QRS duration, it increases Atrial, AV and Ventricular refractory period.

24. Amiodarone: main clinical use It’s a unique wide spectrum anti-arrhythmic drug. Pts with AF where rapid rhythm control is needed. Recurrent ventricular fibrillation. Recurrent haemodynamically unstable ventricular tachycardia.

25. Dose: Oral loading dose 600-1200mg; maintenance dose 200-400mg. IV 150 mg over 10 mins ; then 350 mg over 6 hrs; then 540 mg over 24 hrs. Hepatic metabolism; lipid soluble with extensive distribution in body.

26. Amiodarone : contraindications Cardiogenic shock Severe sinus node dysfunction 2 nd or 3 rd degree AV block. Bradycardia associated with syncope.

27. Amiodarone-adverse effects Toxicity due to accumulation Hepatic, cardiac, pulmonary fibrosis. Thyroid hypo- or hyperthyroidism Skin discoloration Peripheral neuropathy Corneal deposits ↑ Digoxin level Development of new arrhythmia.

28. Class IV – Ca 2+ channel blockers Verapamil & Diltiazem slows AV-conduction rate in patients with atrial fibrillation. ↑PR interval Verapamil – blocks Na + channels in addition to Ca 2+; also slows SA node in tachycardia Suppression of SA node; bradycardia Slowing of AV node: abolish AV reentry Diltiazem Class IV: Drug of choice for SVA: flutter and fibrillation ?

29. Miscellaneous Adenosine I.V bolus (6-12 mg), short t 1/2 15 secs Markedly slows or completely blocks conduction in AV node. Acts by hyperpolarizing AV node through ↑ K + (Ach-sensitive K + channel in SA & AV node) and ↓ Ca +2 currents. Adverse Effects : flushing, hypotension, dyspnea, chest pain, bronchospasm .

30. Drugs of choices S. No Arrhythmia Drug 1 Sinus tachycardia Propranolol 2 Atrial extrasystole Propranolol , 3 AF/Flutter Esmolol , verapamil , digoxin 4 PSVT Adenosine , esmolol , amiodarone 5 Ventricular Tachycardia Lignocaine , procainamide , Amiodarone 6 Ventricular fibrillation Lignocaine , amiodarone 7 A-V block Atropine , isoprenaline