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Copy of sravs

Electrophysiology of the heart

Arrhythmia: definition, mechanisms, types

Drugs :class I, II, III, IV

Guide to treat some types of arrhythmia

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Copy of sravs

  1. 1. Presented by S.Lakshmi Sravanthi 11AB1R0051 Vignan pharmacy college (Approved by AICTE , PCI & Affiliated to JNTU kakinada) Vadlamudi , Guntur (Dt)-522213
  2. 2. Electrophysiology of the heart Arrhythmia: definition, mechanisms, types Drugs :class I, II, III, IV Guide to treat some types of arrhythmia
  3. 3. CARDIAC ARRYTHMIAS Definition  Cardiac arrythmias results from alterations in the orderly sequence of depolarisation followed by repolarization in the heart.  Cardiac arrythmias may result in alterations in heart rate or rhythm and arise from alterations in simple generation or conduction.
  4. 4. ELECTROPHYSIOLOGY – CARDIAC RHYTHM
  5. 5. IMPULSE GENERATION AND CONDUCTION  Conducting tissue • SA node,AV node,bundle of his & purkije fibers. Contractile tissue • Atria and ventricles.
  6. 6. CARDIAC ACTION POTENTIAL  Divided into five phases (0,1,2,3,4) • Phase 0 – rapid depolarization • Phase 1 – early repolarization • Phase 2 – plateau phase • Phase 3 – rapid repolarization • Phase 4 – resting phase, diastolic depolarization
  7. 7. Action Potential Phase 0 Phase 3 Phase 4 Phase 1 Phase 2 30 mV 0 mV - 90 mV Non nodal tissues
  8. 8. 0 1 2 3 4 • Effective refractory period • Absolute refractory period • Relative refractory period 1 0 2 3 4 ARP RRP
  9. 9. Phase 4: pacemaker potential Na+ influx and K efflux and Ca++ influx until the cell reaches threshold and then turns into phase 0 Phase 0: upstroke: Due to Ca++ influx Phase 3: repolarization: Due to K+ efflux Pacemaker cells (automatic cells) have unstable membrane potential so they can generate AP spontaneously
  10. 10. Contraction of atria Contraction of ventricles Repolarization of ventricles
  11. 11. Abnormal impulse generation Triggered activity Abnormal impulse conduction
  12. 12. Abnormal impulse generation  Depressed automaticity of SA node  Enhanced automaticity of SA node  Impulse from ectopic loci  Ischemia, digitalis, catecholamine's, acidosis, hypokalaemia  Less (-) resting membrane potential  More (-) TP
  13. 13. Triggered Activity  Extra abnormal depolarisation - Due to abnormal intracellular Ca2+ regulation - During or immediately after phase 3 - After depolarisation may be categorized in to - Early after depolarisation - Delay after depolarisation
  14. 14. After depolarizations EADs  prolonged APD Clinical arrhythmia: e.g., torsades de pointes due to: long QT syndrome genetic defects DADs  HR or [Ca2+]i Clinical arrhythmia: e.g., Ca2+ overload due to: digoxin or PDE inhibitor toxicity
  15. 15. Conduction block Reentry phenomenon Accessory tract pathway Abnormal impulse conduction
  16. 16. Conduction Block  Due to depression of impulse conduction at AV node & bundle of His, due to vagal influence or ischemia.  Types :  1st degree heart block – slowed conduction  2nd degree block – some supraventricular complex not conducted  3rd degree block – no supraventricular complex are conducted
  17. 17. Re-entry phenomenon  Due to abnormality of conduction , an impulse may recirculate in the heart and causes repetitive activation without the need for any new impulse to be generated. These are called reentrant arrythmias. Circus movement type:  A premature impulse temporarily blocked in one direction by refractory tissue, makes a one-way transit around an obstacle finds the original spot in an advanced state of recovery and rexicites it, setting up recurrent activation of adjacent myocardium.
  18. 18. ACCESSORY TRACT PATHWAY Accessory pathway in the heart called Bundle of Kent
  19. 19. IMPORTANT CARDIAC ARRHYTHMIAS – premature beats  Due to abnormal automaticity or impulse arising from ectopic focus. – Sudden onset of AT 150-200/min  Due to circus movement type of Re-entry or accessory pathway – 200-300 / min  Due to re entry circuit in right atrium
  20. 20. ATRIAL FIBRILLATION o 350-550/min o Due to electrophysiological inhomogenesity of atrial fibers.
  21. 21. – 4 or more consecutive ventricular extrasystoles  Due to either discharge from ectopic focus or reentry circuits  Polymorphic VT with rapid asynchronous complex, twisting along the baseline on ECG with long QT interval  Grossly irregular, rapid & fractionated action of ventrcles – resulting in incoordinated contraction of ventricles with loss of pumping function.
  22. 22. POSSIBLE MECHANISMS OF ANTIARRHYTHMIC DRUGS 1. Suppressing the Automaticity  ↓ Rate of phase 0  ↓ Slope of phase 0  Duration ERP ↑  TP less negative  Resting membrane potential more negative 2. Abolishing reentry  Slow conduction  ↑ ERP
  23. 23. Pharmacological goals  The ultimate goal of antiarrhythmic drug therapy: o Restore normal sinus rhythm and conduction o Prevent more serious and possibly lethal arrhythmias from occurring.  Antiarrhythmic drugs are used to: o Decrease conduction velocity o Change the duration of the effective refractory period (ERP) o Suppress abnormal automaticity
  24. 24. VAUGHAN-WILLIAMS CLASSIFICATION CLASS MECHANISM I Na+ channel blocker II β blocker III K+ channel blocker IV Ca++ channel blocker
  25. 25. Anti arrythmic drugs class mechanism action notes I Na+ channel blocker Change the slope of phase 0 Can abolish tachyarrhythmia caused by reentry circuit II β blocker ↓heart rate and conduction velocity Can indirectly alter K and Ca conductance III K+ channel blocker 1. ↑action potential duration (APD) or effective refractory period (ERP). 2. Delay repolarization. Inhibit reentry tachycardia IV Ca++ channel blocker Slowing the rate of rise in phase 4 of SA node. ↓conduction velocity in SA and AV node
  26. 26. Class I IA IB IC They ↓ automaticity in non-nodal tissues (atria, ventricles, and purkinje fibers) They act on open Na+ channels or inactivated only Use dependence Have moderate K+ channel blockade
  27. 27. IA Quinidine Procainamide Disopyramide Moricizine  Slowing the rate of rise in phase 0  They prolong action potential & ERP  ↓ the slope of Phase 4 spontaneous depolarization  ↑ QRS & QT interval
  28. 28. QUINIDINE  Antimalarial, antipyretic, skeletal muscle relaxant and atropine like action. Mechanism of action • Quinidine binds to open and inactivated sodium channels and prevents sodium influx, slowing the rapid upstroke during phase o. • It also decreases the slope of phase 4 spontaneous depolarization and inhibits potassium channels.
  29. 29.  Diarrhoea  “Cinchonism” – tinnitus, vertigo, headache, nausea & blurred vision. 200-400 mg orally tds C/I AV block QT prolongation - Torsades de pointes Digoxin, enzyme inducer Myasthenia gravis A/E
  30. 30. Uses • Ventricular tachyarrythmias • Used in the termination of ventricular tachycardia Drug interactions • Quinidine can interact the plasma concentration of digoxin, which may in turn lead to signs and symptoms of digitalis toxicity. • Cimitidine increases hepatic metabolism of quinidine
  31. 31. PROCAINAMIDE  Procaine derivative, quinidine like action Mechanism of action  Procainamide binds to open and inactivated Na+ channels and prevents sodium influx, slowing the rapid upstroke during phase 0  Hypotension  Hypersensitivity reaction A/E
  32. 32.  Premature atrial contractions  Paroxysmal atrial tachycardia Dose:1-1.5g rate of 20-50mg/min • Procainamide hypersensitivity • Bronchial asthma • Cimitidine inhibits the metabolism of procainamide Uses C/I Drug Interactions
  33. 33. DISOPYRAMIDE Mechanism of action  Disopyramide produces a negative ionotropic effects that is greater than weak effect exerted by quinidine and procainamide, and unlike the latter drugs, disopyramide causes peripheral vasoconstriction. • Myocardial depression • Urinary retention • Constipation A/E
  34. 34. • ventricular tachycardia • AF & AFI - CHF Disopyramide Uses C/I Drug Interactions  In the presence of phenytoin, the metabolism of disopyramide is increased and the accumulation of its metabolite is also increased, there by increasing the probability of anticholinergic properties.
  35. 35. A/E  Nausea  Dizziness  A-V block Uses  Ventricular tachycardia C/I  A-V block  Drug hypersensitivity MORICIZINE Drug interactions No significant interactions Mechanism of action Moricizine reduces the maximal upstroke of phase 0 and shortens the cardiac transmembrane action potential. The phenomenon may explain the efficacy of moricizine in suppressing rapid ecotopic activity.
  36. 36.  They shorten Phase 3 repolarization  ↓ the duration of the cardiac action potential  Prolong phase 4 IB Lidocaine Mexiletine Phenytoin
  37. 37. LIDOCAINE the duration of action potential decreases  It shorten phase 3 repolarization and decreases the duration of action potential • Drowsiness • Slurred speech • Confusion and convulsions • VA • Digitalis toxicity A/E Uses Mechanism of action
  38. 38. C/I  Lidocaine is contraindicated in the presence of second and third degree heart block, since it may increase the degree of block and can abolish the idioventricular Pacemaker responsible for maintaining the cardiac rhythm. Drug interactions • Proponolol increases its toxicity. • The myocardial depressant effect of lidocaine is enhanced by phenytoin administration.
  39. 39. PHENYTOIN  Phenytoin was originally introduced for the control of convulsive disorders but now also been shown to be effective in the treatment of cardiac arrythmias. Uses  Anaesthesia  Open heart surgery  Digitalized induced and ventricular arrythmia in children
  40. 40. A/E C/I  Respiratory arrest Severe bradycardia  Hypotension Severe heart failure AF & AFI Drug Interactions  Plasma phenytoin concentrations are increased in the presence of chloramphenicol, disulfiram, and isoniazid, since the later drugs inhibit the hepatic metabolism of phenytoin
  41. 41. MEXELETINE Mechanism of action  It is a local anaesthatic and an active antiarrythmic by the oral route; chemically and pharmacologically similar to lidocaine.  It reduces automaticity in PF, both by decreasing phase 4 slow and by increasing threshold voltage.  By reducing the rate of 0 phase depolarization in ischemic PF it may convert one-way block to two-way block.
  42. 42. A/E C/I  Tremor  Hypotension  Bradycardia • Cardiogenic shock • Second or third-degree heart block Uses Drug Interactions • VA • Congenital long QT syndrome • When mexiletine is administered with phenytoin or rifampin, since these drugs stimulate the hepatic metabolism of mexiletine, reducing its plasma concentration.
  43. 43. IC flecainide Encainide Propafenone moricizine  markedly slow Phase 0 depolarization  slow conduction in the myocardial tissue  minor effects on the duration of action potential and ERP  reduce automaticity by increasing threshold potential rather than decreasing slope of Phase 4 depolarization.
  44. 44. FLECAINIDE & ENCAINIDE Mechanism of action  Flecainide suppresses phase 0 upstroke in purkinje and myocardial fibers.  This causes marked slowing of conduction in all cardiac tissues, with a minor effect on the duration of the action potential and refractoriness.  Automaticity is reduced by an increase in the threshold potential rather than a decrease in the slope of phase 4 depolarization
  45. 45.  Proarrhythmogenic efffect on patients with coronary artery disease  Use- ventricular arrhythmia  A/E – torsades de point, visual disturbances & headache  Digoxin toxicity  C/I- cardiogenic shock
  46. 46. PROPAFENONE  Structural similarities with propranolol  C/I – Heart failure  A/E – proarrhythmogenic effect, metallic taste & constipation  150-200mg at 8 hourly  Uses – VT & supra ventricular arrhythmias.
  47. 47. MORICIZINE  Has all three subclass properties  Less proarrhythmogenic effect  Used in ventricular arrhythmias  200-400mg orally at 8hourly
  48. 48. CLASS II DRUGS – PROPRANOLOL, METOPROLOL, ESMOLOL, ACEBUTOLOL Depress phase 4 depolarization depress automaticity prolong AV conduction ↑ ERP Prolong PR interval  HR  contractility
  49. 49. Hypoglycemia (infants) Asthma Branchospasm C/I Asthma Bradycardia Severe CHF PROPANOLOL Mechanism of action  Propanolol decreases the slope of phase 4 depolarization and other ectopic foci. Prolong the ERP of A-V node. Uses  AF Digitalis-induced arrythmias A/E
  50. 50.  Acebutolol is a cardioselective β1-adrenoreceptor blocking agent that also has some minor membrane stabilizing effect on the action potential. Mechanism of action  Acebutolol reduces blood pressure in patients with essential hypotension primarily through its negative ionotropic and chronotropic effects. Acebutolol A/E Bradycardia GI upset Uses • VA • Angina pectoris C/I Cardiogenic shock Severe bradycardia ACEBUTOLOL
  51. 51. ESOMOLOL  Esomolol is a short-acting i.v administered β1-selective adrenoreceptor blocking agent.  It doesn’t posses membrane-stabilizing activity. A/E  Hypotension  Nausea  Headache  Dyspnea Uses  Supraventricular tachyarrythmias C/I  Asthma  Sinus bradycardia  A-V block  Severe CHF
  52. 52. USES Sympathetically mediated arrhythmia Sinus tachycardia Supraventricular arrhythmia – AF / PSVT Ventricular arrhythmia – QT
  53. 53. • K+ channel blockers • AP / ERP without affecting phase 0 / 4 • Prolong QT & PR Class III Amiodarone Bretylium Sotalol
  54. 54. Amiodarone Iodine – containing Block K+ Na+ , Ca++ & β HR & AV nodal conduction  Arrhythmic death in post MI Uses =VF, VT & AF QT prolongation LD-150mg slow IV MD-1mg/min for 6hrs A/E – heart block, pulmonary, hepatitis, dermatitis, corneal deposits & thyroidism Interaction – digoxin, diltiazem & quinidine
  55. 55. Bretylium Antihypertensive Uses-VF & VT C/I – digitalis induced, shock A/E – postural hypotension
  56. 56. Sotalol Like – Amiodarone  Non cardioselective blocker  Has both class II & class III actions  Oral dose 80mg twice daily  Proarrhythmic effect  C/I - hypokalaemia  Arrhythmic death in post MI Uses =VF, VT & AF A/E= fatigue, Headache, chest pain Drug interactions Drug with inherent QT-Interval prolonging activity may enhance the class 3 effects of sotalol.
  57. 57. NEWER CLASS III Dronedarone Vernakalant Azimilide Tedisamil Without iodine, short t1/2, AF Oral 400mg twice daily Na+ & K+, atrial ERP, AF Block both rapid & slow k+ channel
  58. 58. Verapamil Diltiazem Mechanism Class IV • Block L-type calcium channels. •  Rate of phase 4 in SA / AV node • Slow conduction – prolong ERP • Phase 0 upstroke 
  59. 59. Verapamil  Stronger action on heart than smooth muscle  Used in supraventricular arrhythmia  80-120mg three times a day  A/E – ankle oedema, constipation  C/I – AV block, LVF, hypotention & WPW  It  digoxin toxicity Diltiazem  Mixed action  Oral dose 30-90mg 6hourly
  60. 60. WHICH OTHER DRUGS…… Adenosine Naturally occurring nucleoside Adenosine receptors – open GP-K+ & inhibits nodal conduction Used in Reentry circuit, PSVTs & SVT Ultra short t1/2 (10-20 sec) A/E – facial flushing, short breath, bronchospasm, metallic taste Dipyridamole  it’s action 3mg IV bolus
  61. 61. Magnesium Na+/K+ATPase, Na+, K+ & Ca++ VT, digitalis-induced & torsades de point Potassium Normal –  conduction,  ERP &  automaticity Hypokalaemia – EAD & DAD
  62. 62. ARRHYTHMIAS ACUTE THERAPY CHRONIC THERAPY FIRST CHOICE ALTERNATIVES FIRST CHOICE ALTERNATIVES 1 AF/AFL ESMOLOL VERAPAMILE DIGOXIN PROPRANOLOL 2 PSVT ADENOSINE ESMOLOL DILTIZEM VERAPAMIL DIGOXIN VERAPAMILE PROPRANOLOL PROPAFENONE 3 VT LIDOCAINE CARDIOVERSION PROCAINAMIDE MEXILETINE AMIODARONE AMIODARONE DOFETILIDE MEXILETINE PROPRANOLOL PROPAFENONE 4 TORSADES DE POINT PACING ISOPRENALINE MAGNESIUM PROPRANOLOL PACING 5 VF ELECTRICAL DEFIBRILLATION LIDOCAINE AMIODARONE AMIODARONE PROCAINAMIDE DOFETILIDE 6 WPW CARDIOVERSION AMIODARONE PROPAFENONE PROCAINAMIDE AMIODARONE PROPRANOLOL QUINIDINE PROPAFENONE
  63. 63. Drugs that prolong QT interval Antiarrhythimcs Quinidine Procainamide Disopyramide Propafenone Amiodarone Antimicrobials Quinine Mefloquine Artemisinin Sparfloxacin & gatifloxacin Antihistaminics Terfenadine Astemizole Ebastine Antidepressants Amitryptylline Antipsychotics Thioridazine Risperidone Prokinetics Cisapride
  64. 64. REFERENCES o Lippincotts,Pharmacology-IV Edition,Pg.no:196-207 o P.N.Bennet,M.J.Brown,Clinical Pharmacology-IX Edition,Pg no:497-519 o K .D. Tripathi,Essentials Of Medical Pharmacology, Pg.no:508-520 oRang/ dale,Pharmacology, V Edition , Pg no:277-280 o Charles R.Ciaig,Robert E. Stitzel,Modern Pharmacology With Clinical Applications
  65. 65. ACKNOWLEDGEMENT  I thank principal sir Dr. P. Srinivasa Babu for giving me this opportunity.  I Also thankful to my guide Mrs.B.DEEPTI M.Pharm(Ph.D) for her constant guidance.

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