Antiarrhythmic Drugs and its side effect.pptx

It is very important and 3rd and fourth semester pharmacology students

1. Antiarrhythmic Drugs By: Muhammad Aurangzeb Lecturer-INS/KMU

2. By the end of this unit learners, will be able to: Discuss pharmacological management of arrhythmias. Discuss nursing implication in relation to antiarrhythmic drugs. Calculate the drug dosage accurately while administering oral and parenteral medication Objectives

3. Arrhythmia Arrhythmia is deviation of heart from normal rhythm. Normal Rhythm 1)HR- 60-100 Should origin from SA Node Cardiac impulse should propagate through normal conduction pathway with normal velocity.

4. 100 60 Normal range 150 Simple tachyarrythmia 200 Paroxysmal TA . 500 Atrial fibrillation 350 Atrial flutter 40 Mild bradyarrhythmias 20 moderate BA Severe BA Classification o f Arrhythmias

5. Arrhythmias Sinus arrythmia Atrial arrhythmia Nodal arrhythmia (junctional) Ventricular arrhytmia Supra V entricular Tachycardia

6. Types of cardiac tissue (on the basis of impulse generation) Automatic/ pacemaker/ conducting fibers (Ca++ driven tissues) Includes SA node, AV node, bundle of his, purkinje fibers Capable of generating their own impulse Normally SA node acts as pacemaker of heart Non-automatic myocardial contractile fibers ( N a+ driven tissues) Cannot generate own impulse Includes atria and ventricles

7. Electrophysiology of cardiac tissue Impulse generation and transmission Myocardial action potential Depolarization and repolarization waves as seen in ECG

8. Impulse generation and transmission

9. Myocardial action potential In automatic tissues In non-automatic tissues (See video for it) https://www.youtube.com/watch?v=9xSqezCMHnw

10. Arrhythmia Definition: Disturbances in the heart rate, rhythm, impulse generation or conduction of electrical impulses responsible for membrane depolarization These disturbances can lead to alterations in overall cardiac function that can be life threatening. Antiarrhythmic drugs: Compounds used to prevent or treat cardiac arrhythmias

11. Mechanism of arrhythmias Disturbances in impulse generation may be due to Abnormal automaticity Delayed after depolarization Disturbances of impulse conduction The impulse may recirculate in heart causing repeated activation (re-entry) Conduction blocks

12. Re-entry phenomenon

13. Phases of action potential of cardiac cells Phase rapid depolarisation (inflow of Na +) Phase 1 partial repolarisation (inward Na + current deactivated , outflow of K + ) Phase 2 plateau (slow inward calcium current) Phase 3 repolarisation (calcium current inactivates, K + outflow) Phase 4 pacemaker potential (Slow Na + inflow, slowing of K + outflow) ‘autorhythmicity’ Refractory period (phases 1-3) Phase 4 II Phase Phase 1 Phase 3 mV - 80 mV I III IV Phase 2

14. Cont … Phase 0: Fast sodium channels are responsible for initial rapid  depolarization Phase 1: Early fast repolarization (K + efflux) Phase 2: Prolonged depolarization “plateau” due to slow calcium influx Phase 3: Repolarization due to closing of the calcium channels and potassium efflux Phase 4: Resting membrane potential is restored

15. Goals of Treatment The goal of treatment for patients with arrhythmias is preferably to return the heart to sinus rhythm, or failing that, at least to stabilize the rate. Treatment options are pharmacological ( eg , amiodarone, lidocaine, atenolol), ablative (destruction of the malfunctioning tissue) or electrical to correct the rhythm.

16. Drug therapy Anti-arrhythmic drug therapy is used to control the frequency and severity of arrhythmias, with the aim of maintaining sinus rhythm where possible. The drugs can be grouped according to their electrophysiological effects at a cellular level, using a system known as the Vaughan Williams classification . Alternatively , drug therapies can be divided according to their main sites of action within the heart.

17. Vaughan Williams classification All anti-arrhythmic drugs act by altering the movement of electrolytes within the electrical conduction pathways of the myocardium. The Vaughan Williams classification system groups drugs according to their ability to block the movement of one or more of these ions across the myocardial cell membrane.

18. Vaughan Williams Classification of antiarrhythmic drugs Class I: Sodium channel blockers Class II: β- Adrenergic blockers Propranolol, acebutolol, esmolol Class III: Potassium channel blockers Amiodarone, bretylium, sotalol Class IV: calcium channel blockers Verapamil, diltiazem Miscellaneous Adenosine, Digoxin Atropine

19. Class I: Sodium channel blockers Class I drugs act by blocking the fast sodium channels and therefore delay the rise in phase 0 of the action potential . Can be subdivided into: IA : Prolong repolarization, increase the duration of the action potential Quinidine , procainamide, disopyramide IB : Shorten repolarization, shorten the action potential Lignocaine , mexiletine , phenytoin IC : Little effect on repolarization, no effect on action potential duration Encainide , flecainide , propafenone

20. Class I: Sodium channel blockers IA: Prolong repolarization Quinidine , procainamide, disopyramide IB : Shorten repolarization Lignocaine , mexiletine , phenytoin IC : Little effect on repolarization Encainide , flecainide , propafenone

21. Class IA

22. Quinidine D- isomer of quinine obtained from cinchona bark MOA: blocks sodium channels ↓ automaticity , conduction velocity and prolongs repolarization ↓phase depolarization , ↑ APD & ↑ERP Uses: Atrial and ventricular arrhythmias Adverse effects: Arrhythmias and heart block , hypotension, QT prolongation GIT , thrombocytopenia, hepatitis , idiosyncratic reactions High doses – cinchonism like quinine

23. Procainamide: Derivative of procaine No vagolytic or α-blocking action unlike quinidine Better tolerated Adverse effects: Nausea, vomiting and hypersensitivity reactions Higher doses can cause hypotension, heart block and QT prolongation Disopyramide: Significant anticholinergic properties: Dry mouth, blurred vision, constipation, urinary retention

24. Class IB drugs Lignocaine, phenytoin , mexiletine Block sodium channels also shorten repolarization

25. Ligno c aine Local anesthetic Raises threshold for action potential, ↓automaticity Suppress electrical activity of arrhythmogenic tissues, normal tissues less effected High first pass metabolism so given parenterally Use: ventricular arrhythmias Adverse effects: – Drowsiness, hypotension, blurred vision, confusion and convulsions

26. Phenytoin: Antiepileptic also useful in ventricular arrhythmias (not preferred) and digitalis induced arrhythmias Mexiletine: Can be used orally causes dose related neurological adverse events like tremors and blurred vision Nausea is common Used as alternative to lignocaine in ventricular arrhythmias

27. Class I C drugs Encainide, Flecainide, Propafenone Have minimal effect on repolarization Are most potent sodium channel blockers Risk of cardiac arrest , sudden death so not used commonly May be used in severe ventricular arrhythmias

28. Class I drugs and their primary indications Class of drug Drug Primary indication Class 1A Quinidine Procainamide Disopyramide  Atrial fibrillation Ventricular arrhythmias   Class 1B Lidocaine Mexilitene Phenytoin Ventricular arrhythmias Class 1C Flecainide Propafenone  AV nodal re-entry Wolff-Parkinson White syndrome-related arrhythmias Ventricular arrhythmias (but increased risk of mortality

29. Class II drugs Suppress adrenergically mediated ectopic activity Antiarrhythmic action due to of β blockade Depress myocardial contractility, automaticity and conduction velocity Propranolol: Treatment & prevention of supraventricular arrhythmias especially associated with exercise, emotion or hyperthyroidism Esmolol: IV short acting can be used to treat arrhythmias during surgery , following MI & other emergencies

30. ↑APD & ↑RP by blocking the K + channels Class III drugs

31. Amiodarone Iodine containing long acting drug Mechanism of action: (Multiple actions) Prolongs APD by blocking K + channels blocks inactivated sodium channels β blocking action , Blocks Ca 2+ channels ↓ Conduction, ↓ectopic automaticity Pharmacokinetics: Variable absorption 35-65% Slow onset 2days to several weeks Duration of action : weeks to months Many drug interactions

32. Amiodarone Uses: Can be used for both supraventricular and ventricular tachycardia Adverse effects: Cardiac: heart block , QT prolongation, bradycardia , cardiac failure, hypotension Pulmonary: pneumonitis leading to pulmonary fibrosis Bluish discoloration of skin GIT disturbances, hepatotoxicity Blocks peripheral conversion of T4 to T3 can cause hypothyroidism or hyperthyroidism

33. Other Class III Drugs Bretylium: Adrenergic neuron blocker used in resistant ventricular arrhythmias Sotalol: Beta blocker Dofetilide : Selective K + channel blocker, less adverse events Oral use in AF to convert or maintain sinus rhythm Ibutilide : K + channel blocker used as IV infusion in AF or flutter can cause QT prolongation

34. Calcium channel blockers (Class IV) Inhibit the inward movement of calcium ↓ contractility, autom at icity , and AV conduction. Verapamil & diltiazem

35. Verapamil Uses: Terminate PSVT control ventricular rate in atrial flutter or fibrillation Drug interactions: Displaces digoxin from binding sites ↓ renal clearance of digoxin

36. Other antiarrhythmics Adenosine : Purine nucleotide having short and rapid action Mechanism of action: Acetylcholine sensitive K+ channels and causes membrane hyperpolarization through interaction with A 1 type of adenosine GPCRs on SA node IV suppresses automaticity, AV conduction and dilates coronaries Drug of choice for PSVT Adverse events: Nausea, dyspnoea , flushing, headache Atropine: Used in sinus bradycardia , AV block Digitalis: Atrial fibrillation and atrial flutter Magnesium SO 4 : digitalis induced arrhythmias

37. Classification of drug according to principal site of action  Site of action  Anti-arrhythmic drug Action  AV node Verapamil, dilatiazem, adenosine, digoxin, beta-blockers  Delay AV nodal conduction Useful for control of supra-ventricular tachycardias  Ventricles Lignocaine, mexelitine, phenytoin  Control of ventricular arrhythmias  Atria, ventricles and accessory pathways  Quinidine, disopyramide, amiodarone, flecainide, procainamide, propafenone Effective in both supra-ventricular tachycardia and ventricular arrhythmias 

38. Nursing Considerations for Antiarrhythmic drugs Assess for the mentioned contraindications to this drug (e.g. renal dysfunction, heart blocks, hypersensitivity, etc.) to prevent potential adverse effects. Conduct thorough physical assessment before beginning drug therapy to establish baseline status, and to evaluate potential adverse effects. Assess cardiac status closely (e.g. blood pressure, heart rate and rhythm, heart sounds, ec. ) to determine whether change in drug dose is imperative. Monitor laboratory test results including complete blood count, renal and liver function tests to determine the need for possible change in dose and identify toxic effects.

39. N ursing Intervention These are vital nursing interventions done in patients who are taking antiarrhythmic drugs: Titrate the dose to the smallest amount enough to manage arrhythmia to decrease the risk of drug toxicity. Monitor cardiac rhythm closely to detect potentially serious adverse effects and to evaluate drug effectiveness. Ensure maintenance of emergency drugs and equipment at bedside to promote prompt treatment in cases of severe toxicity. Educate patient on drug therapy including drug name, its indication, and adverse effects to watch out for to enhance patient understanding on drug therapy and thereby promote adherence to drug regimen.

40. References Karch , A. M., & Karch . (2011).  Focus on nursing pharmacology . Wolters Kluwer Health/Lippincott Williams & Wilkins. [ Link ] Katzung , B. G. (2017).  Basic and clinical pharmacology . McGraw-Hill Education. Lehne , R. A., Moore, L. A., Crosby, L. J., & Hamilton, D. B. (2004). Pharmacology for nursing care. Smeltzer , S. C., & Bare, B. G. (1992).  Brunner & Suddarth’s textbook of medical-surgical nursing . Philadelphia: JB Lippincott