CLASS 1 ANTI-ARRHYTHMIC DRUGS

A short review by Dr. SWETHA
YOUTUBE LINK FOR AUDIO AND VIDEO-https://youtu.be/cj0bCwx4A_Y

1. CLASS 1 ANTI - ARRHYTHMIC DRUGS Dr . SWETHA

2. INTRODUCTION: CLASS -1 ANTI-ARRHYTHMIC DRUGS are also known as Sodium Channel Blockers.

3. CLASSIFICATION Class-1 Anti- Arrhythmic drugs are further classified as 1a, 1b, 1c based on their mechanism of action, effect on Action Potential Duration, binding and dissociation from sodium channels.

4. Quinidine Disopyramide Procainamide Lignocaine Mexiletine Phenytoin Tocainide Propafenone Moricizine Encainide Flecainide Queen D P L. M. P. Test PM’s EF Class 1a Class 1b Class 1c DRUGS

5. P QRS T NORMAL PHYSIOLOGY P-0:Na + entry into the cell P-1: some K + leaving the cell P-2: Ca +2 entry into the cell P-3: K + leaving the cell rapidly P-0:Rapid depolarization P-1: Early Repolarization P-2: Plateau Phase P-3:Rapid Repolarization P-4:Resting membrane state QRS Complex :ventricular contraction, P-0 T wave : ventricular relaxation, P-3 QT interval-Beginning of depolarization to end of repolarization QT interval = Action Potential Duration Q R S QT interval

6. MECHANISM OF ACTION CLASS 1a ANTI- ARRHYTHMIC DRUGS Membrane potential Time Class 1a - Moderate depression of slope of depolarization Normal ERP APD P Q R S T Widened QRS complex and Prolonged QT interval

7. CLASS-1b ANTI- ARRHYTHMIC DRUGS MECHANISM OF ACTION Cont ….d Membrane potential Time Class 1b-slight depression of slope of depolarization Normal ERP APD P Q R S T QT interval Widened QRS complex and shortened QT interval

8. CLASS 1c ANTI- ARRHYTHMIC DRUGS MECHANISM OF ACTION Cont ….d Membrane potential Time Normal Normal ERP Normal APD P Q R S T QT interval Widened QRS complex and normal QT interval Class 1c Markedly depressed slope of depolarization

9. DIFFERENCES AMONG CLASS 1 ANTI-ARRHYTHMIC DRUGS PROPERTY CLASS 1a CLASS 1b CLASS 1c Na + channel blockade Moderate Weak Powerful Effect on K + channels Block Open No effect Action Potential Action Potential Duration (APD) & Effective Refractory Period(EFP) Increases Decreases Normal Na + channel blockade - 1 c > 1a > 1b Action Potential Duration &Effective Refractory Period-1a > 1c > 1b

10. COMMON PROPERTIES OF CLASS 1 ANTI-ARRHYTHMIC DRUGS

11. QUINIDINE (1a) Isomer of quinine derived from Cinchona bark. PHARMACOKINETICS: Absorbed orally short acting highly plasma protein bound undergoes glucuronidation high 1 st pass metabolism Eliminated by kidneys ATRIAL FLUTTER ATRIAL FIBRILLATIONS VENTRICULAR FIBRILLATIONS CARDIAC USES EXTRA-CARDIAC USES Exhibits anti-malarial, anticholinergic, α - blocking, uterine stimulant and antipyretic properties.

12. QUINIDINE (1a) Cont ….d Torsade's de pointes Thrombocytopenia Hypotension Cinchonism Diarrhea(GI upset) DRUG INTERACTIONS: Reduces D igoxin clearance. E nzyme inhibitor, inhibits CYP2D6, drug like Warfarin, C odeine. Induced by P henytoin, P henobarbitone Plasma quinidine concentration is increased by C imetidine and V erapamil TH,CD D E VIL P C ADVERSE EFFECTS:

13. PROCAINAMIDE (1a) Analogue of Procaine PHARMACOKINETICS: Administered by IV route or oral. Metabolized by Acetylation, Metabolite is N-acetyl procainamide, Metabolism shows genetic variations. Eliminated by kidneys Administered as a loading dose of 10mg/kg at a rate of 20mg/min followed by maintenance dose of 2mg/min. Hypotension Torsade’s de pointes SLE Bone marrow depression Acute Supra ventricular and Ventricular tachyarrhythmias CLINICAL USES: ADVERSE EFFECTS:

14. DISOPYRAMIDE (1a) PHARMACOKINETICS: Absorbed orally. Shows plasma concentration dependent plasma protein binding. Metabolized in liver. Eliminated by kidneys. Also possess anticholinergic activity Useful in reducing muscle mass HOCM ADVERSE EFFECTS: T orsade’s de pointes A nti cholinergic side effects A T Cardiac uses- Extra cardiac uses-

15. LIGNOCAINE (1b) Local anesthetic with anti arrhythmic property. Selectively acts on diseased or ischemic myocardium. PHARMACOKINETICS: Has a rapid onset but short duration of action. IV route is preferred. Metabolized in liver. DRUG OF CHOICE Ventricular Tachycardia Ventricular Fibrillations Digoxin induced arrhythmias Anesthesia induced arrhythmias Arrhythmias in ICU AMI induced arrhythmias ADVERSE EFFECTS: Nystagmus. Drowsiness. Dysarthria Tremors Muscle twitching Convulsions CLINICAL USES:

16. PHENYTOIN (1b) Anti epileptic with anti arrhythmic property. Used as alternative to Lignocaine. Was used previously as drug of choice for digoxin induced arrhythmias. ADVERSE EFFECTS: Potent enzyme inducer. Follows zero-order kinetics at therapeutic concentration. A taxia Nystagmus Mental confusion Hypotension PHARMACOKINETICS:

17. MEXILETINE(1b) Analogue of Lignocaine. TOCAINIDE (1b) Analogue of Lignocaine. Adverse effects include nausea, vomiting, hypotension and neurological such as ataxia, tremors, dizziness, blurred vision. These can be minimized by taking the drug with food Mainly useful in post-MI Ventricular arrhythmias. Other use is phantom limb Adverse effects include bone marrow depression and pulmonary fibrosis. This drug is not used presently. Used in Ventricular arrhythmias. Mexiletine or Tocainide can be used in combination with Quinidine or Sotalol to increase efficacy and reduce toxicity of individual agent.

18. PROPAFENONE (1c) Possess mild β - blocking and calcium channel blocking properties. PHARMACOKINETICS: Well absorbed orally. Metabolism generates 2 metabolites.1)5-hydroxy propafenone(CYP2D6 mediated) 2)N- desalkyl propafenone(weak Na + , β -blocker) Eliminated by liver and kidney. Supra ventricular arrhythmias. Ventricular arrhythmias. Refractory arrhythmias. CLINICAL USES:

19. PROPAFENONE (1c) Cont ….d ADVERSE EFFECTS: Cardiac heart failure. Sinus bradycardia and bronchospasm( β - blocking action) . DRUG INTERACTIONS: Quinidine and Fluoxetine inhibit CYP2D6 mediated metabolism of propafenone in fast metabolizers. Dose should be Hepatic disease . MORICIZINE (1c) Phenothiazine analogue. Useful for chronic treatment of ventricular arrhythmias. Contra-indicated in patients immediately after MI. Not preferred currently.

20. FLECAINIDE (1c) Analogue of Procainamide. Used for re-entrant atrio-ventricular tachycardia(Nodal tachycardia, WPW Syndrome) or any tachycardia due accessory/aberrant pathways from atria/ventricle. Adverse effects: nausea, abdominal discomfort, blurred vision, tremors, dizziness. Contra-indications: Cardiac failure, Sick sinus syndrome and in patients with past history of MI or recovering MI. ENCAINIDE (1c) It is no more used.