3. Circus Movement

4. Classification of antiarrhythmic drugs According to Vaughn-Williams Classification: Class 1: Sodium channel blockersClass 1: Sodium channel blockers Class11: β- adrenoceptor blockersClass11: β- adrenoceptor blockers Class 111: Potassium channel blockers Class 111: Potassium channel blockers

5. Continue Class 1V : Calcium channel blockersClass 1V : Calcium channel blockers  Miscellaneous antiarrhythmic agents

6. Antiarrhythmic Drugs Act on open or inactivated channels Act on open or inactivated channels ( Use -dependence or State – dependence) Have better effect in tissues that are depolarizedHave better effect in tissues that are depolarized

7. Sodium channel blocking drugs Classified into 3 classes according to interaction with sodium channels :Classified into 3 classes according to interaction with sodium channels : Class 1A : intermediate interactionClass 1A : intermediate interaction Class1B : rapid interactionClass1B : rapid interaction Class1C: slow interactionClass1C: slow interaction

8. Drugs of Class 1 A Quinidine is the prototype of this classQuinidine is the prototype of this class ProcainamideProcainamide

9. Continue They possess intermediate rate of association and dissociation with sodium channelsThey possess intermediate rate of association and dissociation with sodium channels Having K+ channel blocking effect.Having K+ channel blocking effect. Are used in treatment of atrial & ventricular arrhythmiasAre used in treatment of atrial & ventricular arrhythmias

10. Effect on action potential Slow phase 0Slow phase 0 Prolong phase 3Prolong phase 3 Result in :Result in : Prolong the duration of action potential & effective refractory period for both atria & ventriclesProlong the duration of action potential & effective refractory period for both atria & ventricles Decrease the slope of phase 4Decrease the slope of phase 4

12. Quinidine Given only orallyGiven only orally Has :Has :  Atropine like action  α- adrenergic blocking effect

13. Clinical uses Atrial flutter & Atrial fibrillation it returns the rhythm back to normal sinus rhythm.Atrial flutter & Atrial fibrillation it returns the rhythm back to normal sinus rhythm. Used in treatment of ventricular arrhythmias.Used in treatment of ventricular arrhythmias.

14. Cardiac adverse effects Cardiac adverse effects A)Paradoxical ventricular tachycardia in atrial flutter or fibrillation in atrial flutter or fibrillation * Quinidine shorten A-V refractory period by its atropine- like effect * Quinidine shorten A-V refractory period by its atropine- like effect (So, Digoxin is given before quinidine) B) A-V block at high plasma level C) Torsade de pointes

16. Extracardiac adverse effects HypotensionHypotension Cinchonism (headache, tinnitus, blurred visionCinchonism (headache, tinnitus, blurred vision GIT( diarrhea, nausea,vomiting)GIT( diarrhea, nausea,vomiting)

17. Drug interactions Quinidine increase the plasma level of digoxin by displacing digoxin from plasma protein binding sites and decreased digoxin renal clearance.

18. Procainamide Given safely by I.M. or I.V. routes.Given safely by I.M. or I.V. routes. Metabolized in liver, giving an active metabolite (NAPA) has potassium channel blocking effect.Metabolized in liver, giving an active metabolite (NAPA) has potassium channel blocking effect.

19. Procainamide(cont.) More effective in ventricular arrhythmias.More effective in ventricular arrhythmias. It is the second drug of choice after lidocaine in the treatment of acute ventricular tachycardia associated with an acute myocardial infarctionIt is the second drug of choice after lidocaine in the treatment of acute ventricular tachycardia associated with an acute myocardial infarction

20. Adverse effects Systemic lupus erythematosus like syndrome.Systemic lupus erythematosus like syndrome. Torsade de pointes Torsade de pointes

21. Class 1B Shorten phase 3 repolarization &duration of action potentialShorten phase 3 repolarization &duration of action potential Suppress arrhythmias mainly due to ectopic focusSuppress arrhythmias mainly due to ectopic focus Show rapid association & dissociation with Na + channels.Show rapid association & dissociation with Na + channels.

23. Drugs of Class 1B LidocaineLidocaine Given only by intravenous routeGiven only by intravenous route

24. Therapeutic uses First drug of choice in the treatment of acute ventricular tachycardia associated with acute myocardial infarction

25. Adverse effects Neurological effects :Neurological effects : Tremors, nausea of central origin, convulsions.

26. Mexiletine Effective orallyEffective orally Long half-lifeLong half-life Mexiletine is used in chronic treatment of ventricular arrhythmias.Mexiletine is used in chronic treatment of ventricular arrhythmias.

27. Adverse effects Neurologic effects as lidocaineNeurologic effects as lidocaine

28. Class1C Interact slowly with sodium channelsInteract slowly with sodium channels Markedly slow phase 0Markedly slow phase 0 No effect on the duration of action potential& refractory period.No effect on the duration of action potential& refractory period.

30. Uses of Class 1C Drugs FlecainideFlecainide  Only approved for refractory ventricular arrhythmias. PropafenonePropafenone  Has weak β-blocking activity  Used in atrial flutter or fibrillation return rhythm to normal sinus rhythm

31. Toxicity of Class 1 C Severe proarrhythmic drugsSevere proarrhythmic drugs Life- threatening ventricular tachycardiaLife- threatening ventricular tachycardia Flecainide increase the mortality rate in patients with premature ventricular contractions following myocardial infarction.Flecainide increase the mortality rate in patients with premature ventricular contractions following myocardial infarction.

33. Class 11: β-drenoceptor blocking drugs Decrease heart rate & cardiac contractilityDecrease heart rate & cardiac contractility Suppress abnormal automaticity & prolong A-V conductionSuppress abnormal automaticity & prolong A-V conduction

34. Uses of Class 11 Drugs 1- Effective in atrial & ventricular arrhythmias that associated with 1- Effective in atrial & ventricular arrhythmias that associated with Increased sympathetic activity Increased sympathetic activity ( High catecholamine states ) ( High catecholamine states ) 2-With quinidine in A.F.& A.F. 2-With quinidine in A.F.& A.F. 3- Effective in preventing post infarct arrhythmias as premature ventricular contraction,they increase survival rate 3- Effective in preventing post infarct arrhythmias as premature ventricular contraction,they increase survival rate

35. Class 11 Drugs Class 11 Drugs o Propranolol –Is used to reduce the sudden arrhythmic death following myocardial infarction o Metoprolol Selective β 1 blocker, used in asthmatic patients. Reduce the rate of mortality due to post infarct arrhythmias.

36. Continue EsmololEsmolol Is a short acting β1 blocking drug.Is a short acting β1 blocking drug. Used mainly for intraoperative acute arrhythmiasUsed mainly for intraoperative acute arrhythmias

37. Class 111:K + channel blockers Prolong the action potential duration & refractory period. Prolong the action potential duration & refractory period. Prolong phase 3.Prolong phase 3.

39. Drugs of class 111 SotalolSotalol AmiodaroneAmiodarone IbutilideIbutilide

40. Sotalol Sotalol Nonselective β- adrenergic receptor blocker.Nonselective β- adrenergic receptor blocker. Is used for the treatment of :Is used for the treatment of : 1- Life- threatening ventricular arrhythmias. 2-To maintain sinus rhythm in patients with atrial fibrillation. 2-To maintain sinus rhythm in patients with atrial fibrillation. 3- For treatment of supra & ventricular arrhythmias in pediatric age group. May induce torsade de pointesMay induce torsade de pointes

41. Ibutilide Given by a rapid I.V. infusionGiven by a rapid I.V. infusion Used for the acute conversion of atrial flutter or atrial fibrillation to normal sinus rhythm.Used for the acute conversion of atrial flutter or atrial fibrillation to normal sinus rhythm. QT interval prolongation, so it precipitates torsade de pointes. QT interval prolongation, so it precipitates torsade de pointes.

42. Amiodarone A) cardiac effectsA) cardiac effects Has a broad actions :Has a broad actions : Sodium channel blockingSodium channel blocking Potassium channel blockingPotassium channel blocking Calcium channel blockingCalcium channel blocking β- adrenoceptor blocking β- adrenoceptor blocking

43. Amiodarone(cont.) B) Extracardiac effectB) Extracardiac effect Peripheral vasodilataion

44. Pharmacokinetics Given orallyGiven orally Slow onset of actionSlow onset of action Long half-life(60 days ).Long half-life(60 days ). Concentrated in many tissues.Concentrated in many tissues. Eliminated by liver mostly as active metabolites.Eliminated by liver mostly as active metabolites.

45. Clinical uses Recurrent ventricular arrhythmias resistant to other drugs. Recurrent ventricular arrhythmias resistant to other drugs. In maintaining sinus rhythm in patients with atrial fibrillation. In maintaining sinus rhythm in patients with atrial fibrillation.

46. Adverse effects Gray- blue skin discoloration Gray- blue skin discoloration Corneal microdeposits  corneal opacity,optic neuritis, blindnessCorneal microdeposits  corneal opacity,optic neuritis, blindness pulmonary fibrosispulmonary fibrosis

47. Adverse effects (cont.) Hypo or hyperthyroidismHypo or hyperthyroidism Gastrointestinal upsetGastrointestinal upset Hepatic toxicityHepatic toxicity ArrhythmiasArrhythmias HypotensionHypotension

48. Class 1V: Calcium channel blockers Verapamil, Diltiazem Verapamil, Diltiazem Their main site of action is A.V.N & S.A.N( slow conduction & prolong effective refractory period ).Their main site of action is A.V.N & S.A.N( slow conduction & prolong effective refractory period ).

50. Class 1V (cont.) They are used in treatment of atrial flutter & fibrillation.They are used in treatment of atrial flutter & fibrillation. They are the second drugs of choice for the treatment of paroxysmal supra-ventricular tachycardiaThey are the second drugs of choice for the treatment of paroxysmal supra-ventricular tachycardia

51. Miscellaneous Drugs Adenosine Adenosine Binds to specific adenosine receptors ( A 1 - purinergic receptors)Binds to specific adenosine receptors ( A 1 - purinergic receptors) decreasing SA & AV nodal automaticity, conduction velocity & prolong effective refractory perioddecreasing SA & AV nodal automaticity, conduction velocity & prolong effective refractory period

52. Pharmacokinetics & Uses Very rapid onset of action. Very rapid onset of action. Short half- life (seconds)Short half- life (seconds) Given as a rapid I.V. bolus injectionGiven as a rapid I.V. bolus injection First choice for the treatment of paroxysmal supraventricular tachycardiaFirst choice for the treatment of paroxysmal supraventricular tachycardia

53. Adverse effects BronchospasmBronchospasm Shortness of breathShortness of breath Chest pain or burningChest pain or burning FlushingFlushing Hypotension.Hypotension.

54. Continue Less effective in the presence of adenosine receptors blockers such as theophylline or caffeineLess effective in the presence of adenosine receptors blockers such as theophylline or caffeine

55. Digoxin Digoxin Treatment of atrial flutter and fibrillation, but not return the atrial rhythm back to normal sinus rhythmTreatment of atrial flutter and fibrillation, but not return the atrial rhythm back to normal sinus rhythm