بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم Antiarrythmic Drugs نأمل أن تحوز المذكرة على رضاكم دعواتكم ستكون بإذن الله سببا في استمرار العطاء فلا تحرمونا... تم التعديل على هذه السلايداتباضافة بعض الفيقرز اللي انشا الله تكون فيه توضيح للفهم ... كل الشكر لبنات 426 اللي كتبوا السلايدات ... كمان كل الشكر لشباب 426 اللي دعموني في تعديل هذي السلايدات وأي احد وده يشارك معانا بالتيم حياه الله اتمنىانها تحوز على رضاكم خالد الشهري GOOD LUCK TO ALL

2. Agents used in cardiac arrhythmias • Normal heart rate • Action potential • ECG

5. Disturbance of cardiac rhythm • Are classified according to : • 1- Site of origin of the abnormality ( atrial , nodal , ventricular ). • 2- Rate ( increased or decreased

6. Factors precipitate arrhythmias • May includes : • Ischemia, hypoxia, electrolytes disturbance, excessive catecholamines exposure , drug toxicity.

7. Mechanisms of arrhythmias • 1- Disturbances in impulse formation. • Vagal stimulation or β- receptor blocking drugs slow normal pacemaker ( reduce the phase 4 slope ). • Acceleration of pacemaker ( increase of phase 4 slope ) by hypokalemia or β-adrenoceptor stimulants. • Development of ectopic pacemakers.-

8. 2- Disturbances in impulse conduction • May result from block ( nodal block or bundle branch block . • Reentry or circus movement • In which one impulse reenters and excites areas of the heart more than ones. • Some forms of reentry are anatomical in shape as in Wolff-Parkinson –White syndrome. “THERE IS AN ACCESORY PATHWAY : ATRIAL ATRIOVENTRICULAR VENTRICULAR , Which has the same direction as the anatomical pathway على حسب الـblock يتغير الطريق

11. Antiarrhythmic Drugs • IN ARRYTHMIA , WE DON’T TREAT ALL THE PTS WITH DRUGS , CUZ ANTIARRYTHMIC DRUGS MAY CAUSE FATAL ARRYTHMIA AND OTHER SIDE EFFECTS - - WE HAVE ALTERNATIVE TREATMENT , eg. SURGERY • Class 1 : Na+ channel blockers “main mechanism” • Local anaesthetic effect • -veinotropic action - -may precipitate heart failure • Class 1( A ): prolongs duration of action potential & refractory period” this happens in atrium and ventricle” • Have K+ channel blocking effect • Antimuscarinic & hypotensive effects “accounts as side effect”

12. . Class1(B):Shorten the duration of action potential because the interaction with Na+ is rapid” blockage and recover” This helps in treatment of ischemic arrhythmia which causes prolonged AP • Class1(C) : No effect on the duration of action or refractory period “cuz of the way of interaction with Na+ “ • Class 11 : β-adrenoceptor blockers. • Class 111: K+ channel blockers, • Prolong duration of action potential and refractory period.

13. Class1V : Ca++ channel blockers. • Verapamil,deltizem,pepridil • Pepridil – acts by other mechanisms : Na+ channel blocking , K+ channel blocking • Only those 3 drugs from all the Ca+ channel blockers can be use as antiarrhythmics. • Ca+ channel blockers has an effect on tissue that depend mainly on Ca+ to produce AP. • Class V: Miscellaneous group.

14. Class 1(A) Quinidine: “used as antimalarial” • Cinchona plant • Cardiac effects: • Block sodium channel • Block potassium channel “prolond duration of AP and RP “ • -veinotropic effect • Antimuscarinic effect “vagolytic or atropine like effect” (increase A.V.conduction). • يشيل تأثير الـparasym على الheart • duration of action potential & refractory periods of atrium & ventricles.

15. ECG changes • Prolong Q-T interval ”cuz it prolongs the RP “ • Widening QRS complex “ cuz it increases the AP of the ventricle”

16. Extra cardiac effects • α- blocking effect (hypotension) • Antimuscarinic effect ( on the heart and other smooth muclses)

17. Phrmacokinetics • Well absorbed orally • High bound to plasma proteins • Metabolized in liver • 20% excreted unchanged in urine • Usually given as slow release formulation • MAIN ROUTE OF ADMINISTRATION IS ORALLY. • I.M. painful,I.V. is toxic • Note: • Route of administration ينعكس على clinical use: • IV –< given in Acute cases • Oral –< given in chronic cases

18. Clinical uses • Atrial flutter & fibrillation it returns the rhythm back to normal “Digitals slow the rhythm but do not return it back to normal” • Used in treatment of ventricular arrhythmia. • NB: Must be preceded by drugs that slow the AV node conduction “cuz this drug increases the conduction through AV node - - ventricular tachycardia “

19. Adverse effects • 1- Cardiac effects • A) Due to antimuscarinic effect ,in A.F.or A.F. may precipitate ventricular fibrillation • B) Syncope( may be caused by polymorphic ventricular tachycardia - - ventricular fibrillation - - - cardiac arrest) • C)Torsade de pointes ) causes : Unknown origin , genetic , electrolyte disturbance , some drugs that increase duration of AP in ventricle , organophosphorus Poisoning (مبيدات حشرية • D) Cardiac stand still(in patients with sick sinus syndrome( tachycardia alternating with bradycardia)).

20. Extracardiac adverse effects • Hypotension • Cinchonism (headache, dizziness,tinnitus,deafness ) • Tinnitus = طنين في الاذن • Hypersensitivity reactions (hepatitis,angioneurotic edema) • GIT, diarrhea,nausea,vomiting • Idiosyncratic reactions including thrombocytopenia

21. Drug interactions • 1-Digoxin ( displace it from plasma protien) • 2-Oral anticoagulant & oral hypoglycaemic drugs ( displace it from plasma protien) • Quinidine increase the plasma levels of both 1&2.

22. Procainamide( comparison with quinidine is imp) • As quinidine but : • Less hypotensive (ganglion blocking effect ) • Less antimuscarinic • Less cardiotoxic • Can be given safely by I.M. or I.V. routes . • Metabolized in liver and give active metabolite (Class 111 activity )

23. Procainamide(cont.) • Eliminated through kidney mainly as active metabolites . • More effective in ventricular arrhythmias , it is the second drug of choice after lidocaine in treament of ventricular arrhythmia follow acute M.I. • Effective in A.F.or A.F. due to Wolff Parkinson White syndrome

24. Wolff-Parkinson-White syndrome ( للفائدة) • (WPW) is a syndrome of pre-excitation of the ventricles of the heart due to an accessory pathway known as the Bundle of Kent. • This accessory pathway is an abnormal electrical communication from the atria to the ventricles

25. Adverse effects • Systemic lupus erythematosus like syndrome. (occur mainly in some people who have problems in acetylating drug) • GIT : Nausea diarrhea • Torsade de pointes

26. Torsades de pointes • A ventricular tachycardia characterized by periodic twisting of the points of the QRS & rates 200 - 250 beats /min.

27. Disopyramide • As quinidine but : • Has marked antimuscarinic effect. • Is only available for oral use • In renal impairment dosage must be adjusted

28. Adverse effects • Can precipitate all of the electrophysiologic disturbance as quinidine. • Potent –Ve inotropic effect on heart may cause heart failure . • Antimuscarinic effects

29. Contraindications • Heart failure • Glaucoma • Prostatic hypertrophy • Constipation • Sick sinus syndrome

30. Clinical uses • Used only (main use)for the treatment of ventricular arrhythmias.

31. Class 1(B) • Lidocaine (also called lignocaine) • It acts as Na blocker & local anesthetic. • Shorten the duration of A.P.& R.P( refractory period). • Effective in ventricular arrhythmias. (especially in purkinji fiber)

32. Pharmacokinetics • Well absorbed after oral administration but subjected to extensive first pass hepatic metabolism, only 3% reach general circulation.(so, it is not used orally) • Given only by I.V. route (important) • Excreted via kidney . • Half-life 2hrs.

33. Therapeutic uses • A)First drug of choice in treatment of ventricular arrhythmias due to • 1-Acute myocardial infarction • 2-Digitalis toxicity • 3-Anaesthesia • 4-Open heart surgery • B)Local anaesthetic drug

34. Adverse effects • 1-Neurological effects : (very IMP) • Paresthesias, tremor,nausea of central origin, convulsions(contraindicated in epileptic patients ). • 2-Arrhythmias (least cardiotoxic of all Na+ channel blockers ). • 3-Hypotension b/c it is vasodilator & has –veionotropic effect

35. Mexiletine • As lidocaine but : • Effective orally • Longer half-life(8-20hrs ). • Used in chronic treatment of ventricular arrhythmias. • Effective in relieving chronic pain due to diabetic neuropathy & nerve injury.

36. Adverse effects • Neurologic ( trmors,blurred vision) . • Nausea

37. Phenytoin • As lidocaine but : • Effctive orally • Weak local anaesthetic effect so does not impair conduction. • As lidocaine is effective in treatment of digitalis induce arrhythmias. • Used to treat arrhythmias in epileptic patients b/c it is mainly an antiepileptic drug . • It has neurological adverse effect BUT not aggravating to cause convulsions.

38. Class1(c) • Flecainide • Has no effect on the duration of A.P.& R.P. • Proarrhythmic drug as it may cause severe exacerbation of arrhythmias even with normal doses.  so it has limited uses nowadays • Used in supraventricular arrhythmias in patients with normal hearts.

39. Propafenone • Has a weak β-blocking effect. • Used for supraventricular arrhythmias.( atrial NOT ventricular arrythmia) • The most common adverse effects are : • Metallic taste, constipation ,arrhythmias.

40. Moricizine • Has long half-life • Used for ventricular arrhythmias • Common adverse effects are : • Dizziness ,nausea ,arrhythmias.

41. Class 11 • Beta-Adrenoceptor-Blocking Drugs. • Effective in atrial & ventricular arrhythmias that associated with : • 1-Increase in sympathetic activity e.g.emotion,stress,thyrotoxicosis. • 2-Digitalis induce arrhythmias. • 3-With quinidine in A.F.& A.F. • 4-Esmolol is a short-acting used mainly for intraoperative &acute arrhythmias.

43. Class 111 • Potassium channel blockers • ( Drugs that Prolong duration of action potential & refractory period ).

44. Bretylium • Has β- blocking effect. • Initial release of catecholamines so may precipitate ventricular arrhythmias initially. • Available only for intravenous use. • Used in an emergency cases as during attempted resuscitation from ventricular fibrillation when lidocaine or when cardioversion failed.

45. Adverse effects • Arrhythmias • Postural hypotension b/c 1- direct action 2- release of catecholamine • It has β-blocking effect. • Nausea & vomiting not important side effect b/c it is given IV emergency.

46. Sotalol • Has β-blocking effect. • Is used for the treatment of : • 1-Life- threatening ventricular arrhythmias. • 2-To maintain sinus rhythm in patients with atrial fibrillation. • 3- For treatment of supra & ventricular arrhythmias in pediatric age group.

47. Dofetilide • Most recent drug which has selective K+ blocking effect & has no other action • Given orally • Excreted unchanged through the kidney. • Used to restore normal sinus rhythm in patients with atrial fibrillation & flutter in patients with recent MI & poor LV function. • Causes torsade de pointes ( prolong Q-T interval )العيب الوحيد فيه.so u should make ECG regularly if prolong Q-T manage the problem

48. Ibutilide • Given by I.V. infusion • Excreted mainly as metabolites by kidney. • Used for the acute conversion of atrial flutter or atrial fibrillation to normal sinus rhythm. • Causes prolongation of Q-T interval, so it precipitate torsade de pointes.

49. Amiodarone • A) cardiac effects • Has a broad actions: (cause more adverse effect) • Sodium channel blocking effect • Potassium channel action • Calcium channel blocking action • β- adrenoceptor blocking action

50. Amiodarone(cont.) • B) Extracardiac effect • Peripheral vasodilation