1 / 66

Chapter 30 Antiarrhythmic Drugs

Chapter 30 Antiarrhythmic Drugs. arrhythmias. A. Electrophysiological basis of arrhythmias. 1. Normal cardiac electrophysiology Excitability: ability to produce action potentials maximal diastolic potentials (MDP)

allysonf
Download Presentation

Chapter 30 Antiarrhythmic Drugs

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Chapter 30Antiarrhythmic Drugs

  2. arrhythmias

  3. A. Electrophysiological basis of arrhythmias • 1. Normal cardiac electrophysiology • Excitability: ability to produce action potentials • maximal diastolic potentials (MDP) • thresold levels • Automaticity: pacemaker • phase 4 slope • Conductivity: conduction pathways, • phase 0 amplitude

  4. Action potential and ion transport Fast response cell

  5. Action potential and effective refractory period

  6. Pacemaker and conduction systems in the heart

  7. Impulse generation and conduction in the heart

  8. A. Electrophysiological basis of arrhythmias • 2. Slow and fast response cells • Slow response cells：pacemaker cells • fast response cells：conduction and contraction cells Fast response Slow response phase 4 potential －90 mV －70 mV depolarizationNa+, 120 mV, 1-2 ms Ca2+, 70 mV, 7 ms automaticitylow（0.02 V/s） high（0.1 V/s） conductionfast（200-1000 V/s） slow（10 V/s） effects conductionpacemaker

  9. Slow response Action potentials of slow and fast response cells Fast response ECG

  10. A. Electrophysiological basis of arrhythmias • 3. Abnormal generation of impulse • (1) Augmented automaticity • Augmented automaticity in the myocardial cells other than the sinoatrial node cells will produce arrhythmias • Maximal diastolic potential (MDP) in phase 4:ischemia, digitalis, sympathetic excitation, imbalance of electrolytes • Fast spontaneous depolarization in phase 4：fast response cells  slow response cells

  11. a.increased phase 4 slope Slow response cells b.decreased thresold levels

  12. A. Electrophysiological basis of arrhythmias • (2) Afterdepolarization and triggered activity • early afterdepolarization (EAD)： • phases2, 3; • longer Q-T interval (Torsades de Pointes); • Ca2+ inward flow increases • induced by drugs, plasma K+ • delayedafterdepolarization (DAD)： • phase4; • Ca2+ inward flow leads to transient Na+ inward flow • induced by digitalis intoxication, plasma Ca2+, K+

  13. Triggered beat Triggered beat A.early afterdepolarization (EAD) B.delayed afterdepolarization (DAD)

  14. A. Electrophysiological basis of arrhythmias • 4. Abnormal conduction of impulse • (1) Simple conduction block • slow and small depolarization in phase 0, reduced MDP level in phase 4 • MDP  in ischemia, inflammation, metabolic disorders； • Usually occurred in atrioventricular regions

  15. A. Electrophysiological basis of arrhythmias • (2) Reentrant reexcitation (reentry) • Circuits (especially in enlarged ventricles) • ( Wolff-Parkinson-White syndrome) • Unidirectional (one-way) block • (myocardial injury) • Slow conduction • Heterogeneity in ERP

  16. Abnormal conduction pathway of Wolff-Parkinson-White syndrome

  17. B. Electrophysiological effects and classification of antiarrhythmic drugs • 1.Electrophysiological effects of antiarrhythmic drugs • (1) Reducing abnormal automaticity • decreasing phase 4 slope • increasing thresold levels • increasingMDP levels in phase 4 • increasing action potential duration（APD）

  18. A.decreasing phase 4 slope • B.increasing thresold levels • C. increasing MDP levels in phase 4 • D.increasing action potential duration（APD） fast response cells

  19. b.decreasing phase 4 slope Slow response cells c.increasing thresold levels；d.increasing MDP

  20. B. Electrophysiological effects and classification of antiarrhythmic drugs • class IV drugs decrease automaticity of slow response cells • class I drugs decrease automaticity of fast response cells • class II drugs decrease the augmented automaticity caused by sympathetic excitation

  21. B. Electrophysiological effects and classification of antiarrhythmic drugs • (2) inhibiting afterdepolarization and triggered activity • EAD：repolarization  (class IB), • inward current  (class I, IV) • DAD：class IV, I • Sympathetic excitation or digitalis：class II

  22. B. Electrophysiological effects and classification of antiarrhythmic drugs • (3) Modulating conduction • Accelerating conduction • Abolishing reentry • one-way block  two-way block • abolishing one-way block

  23. One-way blockreentry normal Two-way block abolishing block

  24. B. Electrophysiological effects and classification of antiarrhythmic drugs • (4) Modulating effective refractory period (ERP) • prolonged ERP • prolonged ERP/APD • homogeneity of ERP

  25. Reducing membrane responsiveness increasing APD and ERP

  26. B. Electrophysiological effects and classification of antiarrhythmic drugs • 2.Classification of antiarrhythmic drugs Prolongation of repolarization

  27. (1) Class I • (Na+ channel blockers) • Class IA： • moderately block Na+ channels, • conduction , • APD and ERP  • quinidine 奎尼丁 • procainamide 普鲁卡因胺

  28. Class IB： • mildly block Na+ channels, • no markedly inhibition on conduction, • K+ outward flow  • shorten repolarization • lidocaine 利多卡因 • phenytoin 苯妥英

  29. Class IC： • markedly block Na+ channels, • depolarizaton verosity in phse 0  • conduction  • no marked effect on repolarization • propafenone 普罗帕酮 • flecainide 氟卡尼

  30. B. Electrophysiological effects and classification of antiarrhythmic drugs • (2) Class II ( receptor blockers) • propranolol 普萘洛尔 • (3) Class III (prolongation of repolarization) • amiodarone 胺碘酮, sotalol 索他洛尔 • (4) Class IV (Ca2+ channel blockers) • verapamil 维拉帕米

  31. B. Electrophysiological effects and classification of antiarrhythmic drugs • Class I（Na+ channel blockers） • IA SV, V • IB V • IC SV, V • Class II（ receptor blockers）SV*, V • Class III（prolongation of repolarization）SV, V • Class IV（Ca2+ channel blockers）SV*, V * primary action sites

  32. Effects of antiarrhythmic drugs on mortality

  33. C. Antiarrhythmic drugs • Class I drugs:Na+ channel blockers • Class IA drugs Quinidine 奎尼丁

  34. C. Antiarrhythmic drugs • 1. Pharmacological effects • Na+ channel block • muscarinic receptor block • (1) Automaticity： • depolarization slope in phase 4  • abnormal automaticity  • (2) Conduction : direct action, one-way  two-way block • atrioventricular conduction  because of M receptor block • (3) ERP and APD： ERP , APD , ERP/APD  • (4) Other effects: hypotension: α receptor block

  35. C. Antiarrhythmic drugs • 2. Clinical uses • (1) Atrial fibrillation and flutter, pre- and post-cardioversion • conversion to sinus rhythm (pretreated with digitalis) • maintaining sinus rhythm • (2) Other arrhythmias • ventricular and supraventricular arrhythmias

  36. C. Antiarrhythmic drugs • 3. Adverse effects • (1) Extracardiac effects:GI reactions, • hypotension, • Chichonism, • allergy • (2) Cardiac toxicity:prolongedQRS and QT intervals, • quinidine syncope, • paradoxical ventricular tachycardia • (3) Arterial embolism:after cardioversion

  37. C. Antiarrhythmic drugs • 4. Drug interactions • (1) Hepatic enzyme inducers (barbiturates, phenytoin, etc.):increase the metabolism of quinidine • (2) Hepatic enzyme inhibitors (cimitidine, verapamil, etc.):decrease the metabolism of quinidine • (3) Combined with digoxin:reducing the dose of digoxin

  38. C. Antiarrhythmic drugs Procainamide 普鲁卡因胺 Effects and uses are similar to quinidine, but weak to atrial fibrillation and flutter induces GI reactions, hypotesion, allergy, occasionally systemic erythematosus lupus (long-term use)

  39. C. Antiarrhythmic drugs • Class IB drugs Lidocaine 利多卡因

  40. C. Antiarrhythmic drugs • 1. ADME • Low bioavailability after oral administration • Rapid elimination after i.v. injection • Given by i.v. infusion ( i.v. gtt )

  41. C. Antiarrhythmic drugs • 2. Pharmacological effects • (1) Automaticity：reducing spontaneous depolarization in phase 4 of Purkinje fibers • (2) Conduction: • therapeutic dose: no remarkable effects • larger doses, K+, pH  : decrease • MDP , K+ : increase • (3) APD and ERP：Na+ inward flow  in phase 2 • K+ outward flow  in phase 3 • ERP , APD  , ERP/APD 

  42. C. Antiarrhythmic drugs • 3. Clinical uses • Ventricular arrhythmias: • acute myocardial infarction • intoxication of digitalis • general anesthetics, etc.

  43. C. Antiarrhythmic drugs • 4. Adverse effects • (1) CNS depression • (2) Hypotension • (3) Arrhythmias:bradycardia, A-V block

  44. C. Antiarrhythmic drugs Phenytoin Sodium 苯妥英钠 Effects and uses are similar to lidocaine More effective on digitalis toxicity because of competition to Na+-K+-ATPase

  45. C. Antiarrhythmic drugs • Class IC drugs Propafenone 普罗帕酮

  46. C. Antiarrhythmic drugs • 1. Pharmacological effects • Reducing automaticity and conduction of fast response cells in atrium and Purkinje fibers • 2. Clinical uses • Supraventricular and ventricular arrhythmias • 3. Adverse effects • GI reactions, postural hypotension, arrhythmias

  47. C. Antiarrhythmic drugs Flecainide 氟卡尼

More Related