PHARMACOLOGY OF ANTI-ARRHYTHMICS

1. PHARMACOLOGY OF ANTI-ARRHYTHMICS

2. Arrhythmia (a-rhythm) means no rhythm,whereas dysrhythmia (dys-rhythm) means an abnormal heart rhythm. In practice,both terms are used interchangeably to mean an abnormal of irregular heart beat. Arrhythmia

3. Cardiac arrhythmias 25% with digitalis 50% Aneathetized patients over 80% with acute myocardial infarction

4. Genesis of Normal Heart Rhythm Genesis of Tachyarrhythmia HeartRhythm Managing Tachyarrhythmias Antiarrhythmic Drugs

5. Genesis of Normal Heart Rhythm: The Myocardial Action Potential

6. (1) pacemaker activity(2) absence of fast Na+ current in SA and AV nodes, where slow inward Ca2+ current initiates action potentials. (3) long action potential ('plateau') and refractory period (4) influx of Ca2+ during the plateau. Electrophysiological Features

7. Phase-4 Depolarizationresults in automaticity of the cardiac action potential, in normal SA nodal cells.

11. The Effective Refractory Period(ERP)

12. Genesis of Normal Heart Rhythm : Ion Channel

13. 1 Classification of Arrhythmias 2 Enhanced Automaticity 3 Reentry 4 Afterpotentials Genesis of Tachyarrhythmia

14. Classification of Arrhythmias Bradyarrhythmias Tachyarrhythmias

16. Unidirectional Block and Reentry

17. Late After Depolarization

18. Managing Tachyarrhythmias: Strategies Sufficient Preparation Suppress enhancedautomaticity Prolong Effective Refractory Period Slow conduction in tissue • Depress resting membrane • potential

24. Na+ Channel Blockers • β-adrenergic Blockers • Prolong ERP • Ca2+ Channel Blockers • Adenosine • Digoxin Class III Class I Class II Class IV Classification of Antiarrhythmic Drugs (Vaughan-Williams)

25. Classification of antiarrhythmic drugs

26. Class I: Na+ Channel Blockers

27. Class I: Na+ Channel Blockers Guinidine

29. Class II Antiarrhythmic Drugs: β1-adrenoceptor blockers

30. How Sympathetic Stimulation Increases Heart Rate and Accelerates Conduction:

31. Non-pacemaker Tissue:Sympathetic activity→Accelerated Conduction

32. Pacemaker:β- adrenoceptor stimulation:→ ↑ automaticity

33. Class II: β-adrenergic Blockers: Oppose effects of sympathetic tone • Reduce automaticity (including physiological) • Slow conduction • Mainly active in atrial & atrioventricular tissue • Reduce risk of sudden death after heart attack

34. Class II: Examples •Propranolol • Metoprolol • many other -olol’s • Other aspects of pharmacology: look up autonomic pharmacology notes

35. Class III: Drugs that Prolong Action Potential Duration & ERP

38. Class III: Examples • Amiodarone 胺碘酮 • Sotalol 索他洛尔 (also β-blocker)

39. Class IV Calcium Channel Blockers (also active in angina and hypertension)

40. Adenosine • Adenosine receptors on atrial myocardium and atrioventricular conducting tissue • K+ channels are adenosine receptor-linked

43. Adenosine: Pharmacology • Very rapid hydrolysis in blood – only IV use – rapid IV bolus • For supraventricular tachycardias (may help diagnosis)

44. Effects of antidysrhythmic drugs on the different phases of the cardiac action potential

45. Thank you!!