Dr P.V.Nishanth,MD,DNB.    NIMS,Hyderabad.
   A transmembrane electrical gradient (potential) is    maintained, with the interior of the cell negative with    respe...
   Divided into five phases (0,1,2,3,4)    ◦ Phase 4 - resting phase (resting membrane potential)       Phase cardiac ce...
   Phase 2 - plateau phase    ◦ sustained by the balance between the inward movement of Ca+ and      outward movement of ...
   Once an AP is initiated,    there is a period (phase    0,1,2, part 3) that a new AP    cannot be initiated.   Effect...
   Fully repolarized -60mv   No stable RMP   Phase 4: Spontaneous    depolarization or    pacemaker potential   Slow, ...
   -50mV T-type CaCh open   Ca in: further depolarizes   -40 mV L-type CaCh open   More Ca in: further depol   AP thr...
   Phase 3:    Repolarization   K+ channels open   Increase the outward    hyperpolarizing K+    currents   At the sam...
   PCs - Slow, continuous depolarization during rest   Continuously moves potential towards threshold for a    new actio...
   SNS - Increased with concurrent    inhibition vagal tone:    NA binds to B1 Rec   Increases cAMP   Increases Ca and...
   PSNS (Vagal N)   Ach binds M2 rec   Increases gK+   Decreases inward Ca & Na   Pacemaker current (If)    suppresse...
    Restore normal rhythm, rate and conduction or     prevent more dangerous arrhythmias1.   Alter conduction velocity (S...
   Block open ACTIVATED Na channels   Slow phase 0 depolarisation - upstroke of AP   Lengthen APD and ERP.   Prolong Q...
 suppresses automaticity in normal Purkinje fibers Little effect on normal sinus node Peripheral vasodilatation may ref...
 Suppresses premature SV/V ectopics Conversion and maintainence of atrial  flutter/fibrillation into sinus rhythm. Can ...
 I.V- 6 to 10 mg/kg at 0.3 to 0.5 mg/kg/min oral— 800 to1000mg-loading Maintainence- 300 to 600q6hr Half life- 5 to 9 ...
 syncope in 0.5 to 2.0 percent of patients, most  often the result of a self-terminating episode of  torsades de pointes...
 Magnesium given intravenously (2 gm over 1 to 2  minutes, followed by an infusion of 3 to 20  mg/min) is the initial dru...
 Least anti cholinergic of class 1 agents Can depress myocardial contractility in high doses
 NAPA elimination half life is 7-8hrs and is  excreted only by kidney Procainamide is ecreted both by kidney and liver ...
 SVT-convert AF to sinus In patients with AF and rapid conduction over  accessory pathway Can terminate sustained VT be...
 IV loading-6 to 13 mg/kg at 0.2 to 0.5 mg/kg/min Maintainence-2 to 6 mg/min Oral loading-500 to 1000 mg Maintainence-...
 Noncardiac adverse effects from procainamide  administration include rashes, myalgias, digital  vasculitis, Raynauds phe...
 Doses are generally 100 to 200 mg orally every 6  hours, with a range of 400 to 1200 mg/day Adverse effects-vagolytic ...
 Good Na channel block with weak K channel  blocking property mean elimination half-life of 13 min in most  patients, ma...
 When administered IV at doses of 50 mg over 3  min, or 10 mg/minute, to a total dose of 1 mg/kg,  ajmaline can have the ...
 (2) ST-T abnormalities and interventricular  conduction blocks in patients with occult chagasic  cardiomyopathy (3) hea...
 Block INACTIVATED Na channels Slow phase 0 depolarisation- Slows upstroke  of AP Shorten APD and ERP Ratio ERP/APD is...
 does not affect normal sinus node automaticity does depress other normal and abnormal forms of  automaticity, as well a...
   Metabolised in liver ,metabolism inhibited in    cardiac failure and half life increased to 4 hrs ,in    uncomplicated...
 initial bolus of 1 to 2 mg/kg body weight at a rate  of 20 to 50 mg/min, with a second injection of half  the initial do...
 To treat arecurtrence arrythmia 6-8 hrs later give  another bolus and then increase infusion rate If the initial bolus ...
 To treat ventricular arrythmias. Not useful for supra ventricular arrythmias dose-related manifestations of central ne...
 can result in severe bradycardia and abnormal  sinus node recovery time in patients with sinus  node disease rapidly an...
 starting dose is 200 mg orally every 8 hours when  rapid arrhythmia control is not essential May be increased or decrea...
 moderately effective antiarrhythmic agent for  treating patients with acute and chronic ventricular  tachyarrhythmias M...
 Neurological Cardiac-bradycardia Dose related Therapeutic plasma levels - 0.5 to 2 mg/ml
 In arrythmias caused by digitalis toxicity Prevents delayed after depolarisations 100 mg of phenytoin should be admini...
 Block Na channels. Most potent Na channel block Dissociate very slowly (10-20 sec) Strongly depress conduction in myo...
 marked drug effects can occur at physiological  heart rates Flecainide shortens the duration of the Purkinje  fiber act...
 Anterograde and retrograde refractoriness in  accessory pathways can increase significantly in a  use-dependent fashion...
 starting dose is 100 mg every 12 hours, increased  in increments of 50 mg twice daily, no sooner than  every 3 to 4 days...
 ventricular tachyarrhythmias, SVTs, and  paroxysmal atrial fibrillation Useful as adiagnostic tool in brugada sybdrome
 marked slowing of conduction precludes its use in  patients with second-degree AV block without a  pacemaker and warrant...
 PROPAFENONE conduction slowing is the major effect depresses sinus node automaticity and A-H, H-V,  PR, and QRS interv...
 dizziness, disturbances in taste, and blurred vision  the most common and gastrointestinal side effects  next. Exacerba...
 prolongs AV node and His-Purkinje conduction  times and QRS duration. Ventricular refractoriness is prolonged slightly,...
   designed as a multicenter, randomized, placebo-    controlled trial to test the hypothesis that in    patients with pr...
 As data were gathered, it became evident that  encainide and flecai nide worsened survival, and  these two arms of the t...
 Role of tachycardia in precipitating arrythmias Increased sympathetic activity in patients with  sustained VT Role of ...
 Hyperpolarisation (if) current-proarrythmic  depolarisation in damaged to heart tissue Inward (L type) calcium current ...
 slows spontaneous automaticity in the sinus node  or in Purkinje fibers that are being stimulated by  adrenergic tone, p...
 sinus discharge rate in humansdecreases by 10 to  20 percent The PR interval lengthens, as do AV nodal  conduction time...
 Propanolol,sotalol acebutolol approved Metoprolol was tried in arrythmia suppression  trials like the one by stienbeck...
 Pharmacokinetics:Propranolol is almost 100  percent absorbed, but the effects of first-pass  hepatic metabolism reduce b...
   Arrhythmias associated with thyrotoxicosis,    pheochromocytoma, and anesthesia with    cyclopropane or halothane or a...
 Terminate or prevent recurrence of tachycardias  like-AVNRT and orthodromic reciprocating  tachycardias in the Wolff-Par...
 effective for digitalis-induced arrhythmias(watch  for AV block) arrhythmias associated with the prolonged QT  interval...
 ADVERSE EFFECTS unacceptable hypotension, bradycardia, and  congestive heart failure Raynauds,bronchospasm,insomnia,lo...
 CASH EVSEM
   CASH (Randomized Comparison of    Antiarrhythmic Drug Therapy With Implantable    Defibrillators in Patients Resuscita...
 This study was designed to evaluate impact of the  ICD vs antiarrhythmic drugs (amiodarone,  metoprolol, propafenone), o...
 23% reduction (statistically nonsignificant) in the  all-cause mortality rate was seen in the ICD group  compared with t...
 Propranolol 0.25 to 0.5 mg q5 min to 0.20 mg/kg Oral-10 to 200 q6- 8hr Time to peak conc.-4 Effective serum conc.-1 t...
 Esmolol-IV 500µg/min loading dose over 1min Use steps of 50/100/150/200µ/min over 4 min  each Half life-9 min Onset-2...
   Block K channels   Prolong repolarisation   Prolong APD and ERP   Useful in Re-Entry tachycardias   AMIODARONE (al...
 Initially developed in the early 1960s as a  treatment for angina pectoris, since it produces  coronary vasodilation and...
 Structural similarities to the thyroid hormones Absorption is limited (30-50%) Metabolised in the liver to produce the...
 elimination half-life after oral long term treatment  is 50-60 days 200mg dose-7mg /d of iodine is released Into  body(...
 Class-3-acts on K channels-prolongs action  potential and prolongs ERP Class-1-blocks inactivated Na channels-more at  ...
 slows sinus rate and atrioventricular conduction prolongs the QRS duration ,notably prolongs the  QT interval. Abnorma...
 Useful for both SVT and VT AF- two trials-canadian trial and DIONOSYS trial  showed superior efficacy of amiodarone in ...
 Ventricular arrythmias- Useful in out of hospital VF and refractory VT  following cardiac surgery Similar/superior eff...
 SCD-HeFT-EF<35%-similar all cause mortality to  placebo but higher compared to ICD EMIAT- SCD In post MI with decreased...
 IV- 15 mg/min for 10 min, 1 mg/min for 3 hr, 0.5  mg/min thereafter till 24hrs Maintainence doses-1 mg/min Oral loadin...
 Increase serum levels-digoxin  anticoagulants statins CCBS Tacrolimus Quinidine fentanyl flecainide
 Prevalence of 15% in the first year, increasing up  to 50% during long term use. 20 -50% of patients, the drug must be ...
200 mg the incidence is   0.1-1.6%, which increases with higher                                     doses              18-...
Erythematous  iscoloration with a b           luish shadeDue to prolonged high    dose tretment and lipofuscin deposition ...
corneal deposits-excretion in lacrimal fluid  Halo vision-necessiate               withdrawlOptic neuritis-occurs 4mon -1 ...
 First licensed for control of severe ventricular  arrythmias Non cardio selective water soluble protien bound  agent wi...
 Racemic mixture L-sotalol has class 2 effects-SA and AV node  depression D- sotalol has class 3 effects-prolongs APD i...
 Indications-PSVT,WPW, preventing recurrence of  AF,ischemic VT, Major trial was EVSEM trial-in decreasing death  and ar...
 oral dose is 80 to 160 mg every 12 hours, allowing  2 to 3 days between dose adjustments to attain a  steady state and t...
   Major side effect-torsades de pointes increases to    4 percent in patients with a history of sustained VT    and is d...
 prolongs repolarization it also activates a slow inward sodium current  along with block outward potassium currents, su...
 Given intravenously and has a large volume of  distribution. Clearance is renal, with a half-life of 6 hours IV infusi...
 termination of an established episode of atrial  flutter or fibrillation,but not for short paroxysms or  prevention of r...
 prolongs accessory pathway refractoriness and  can temporarily slow the ventricular rate during  preexcited atrial fibri...
 Side effects and precautions Torsades is imp. Side effectoccur in approximately  2 percent of patients given the drug (...
 approved for acute conversion of atrial fibrillation  to sinus rhythm, as well as chronic suppression of  recurrent atri...
 absorbed well, with over 90 percent bioavailability. Fifty to 60 percent of the drug is excreted  unchanged in urine, w...
 prevention of episodes of supraven-tricular  tachyarrhythmias, particularly atrial flutter and  fibrillation Chemical c...
 Drugs which increase its concentration are  ketoconazole,macrolides,protease inhibitors Additive effect with other drug...
 balanced blockade of both rapid and slow  components of IK. effect is responsible for the lower rate of  proarrhythmia ...
 orally once daily, and its absorption is nearly  complete and unaffected by food intake once daily at a dosage of 100 t...
 Calcium Channel Blockers Bind to L-type Ca channels Vascular SmM, Cardiac nodal & non-nodal cells Decrease firing rat...
   Narrow complex tachycardias   Terminates PSVT/SVT   Rate control in AFib/Aflutter   NOT WPW or VT or high degree bl...
•   Acts via the adenosine A1 receptor•   activation of an outward potassium current    (IKADO and IKACH) present in the a...
 In the N region of the AV node, conduction is  depressed, along with decreases in action  potential amplitude, duration,...
•   Pharmacokinetics:•   Half life-10-30sec•   Metabolised by erythrocytes and vascular    endothelial cells.•   Dose-•   ...
 Interactions: methylxanthines are competitive antagonists, and  therapeutic concentrations of theophylline totally  blo...
 AV node and AV reentry Can terminate SA node reentry RVOT VT-inhibition of catecholamine stimulated  calcium currents
 Useful in distinction between SVT with aberancy  and VT differentiating conduction over the AV node from  that over an ...
 Side effects: most commonly flushing, dyspnea, and chest  pressure-lasting less than 1 minute, and are well  tolerated....
 Asthma or h/o asthma 2nd or 3rd degree AV block Sick sinus syndrome
 enhancing both central and peripheral vagal tone actions are largely confined to slowing the sinus  node discharge rate...
 Serum half-life of digoxin is 36 to 48 hours, and  the drug is excreted unchanged by the kidneys Acute Loading dose is ...
 Mainly for control of ventricular rate in Aflu/Afib In exercise diminution of vagal tone and increase  in sympathetic t...
 headache, nausea and vomiting, altered color  perception, halo vision, and generalized malaise Cardiac –digitalis effec...
   bradycardias relatedto a markedly enhanced    vagal effect (e.g., sinus bradycardia or arrest, AV    node block)-withd...
 Tachyarrhythmias-DAD-PAT with varying block,  junctional, and fascicular or ventricular tachycardia-  Phenytoin can be u...
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
Antiarrythmic drugs review
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Antiarrythmic drugs review

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A transmembrane electrical gradient (potential) is maintained, with the interior of the cell negative with respect to outside the cell.Caused by unequal distribution of ions inside vs. outside cell ,Na+ higher outside than inside cell,Ca+ much higher “ “ “ “
K+ higher inside cell than outside Maintenance by ion selective channels, active pumps and exchangers

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Antiarrythmic drugs review

  1. 1. Dr P.V.Nishanth,MD,DNB. NIMS,Hyderabad.
  2. 2.  A transmembrane electrical gradient (potential) is maintained, with the interior of the cell negative with respect to outside the cell Caused by unequal distribution of ions inside vs. outside cell ◦ Na+ higher outside than inside cell ◦ Ca+ much higher “ “ “ “ ◦ K+ higher inside cell than outside Maintenance by ion selective channels, active pumps and exchangers
  3. 3.  Divided into five phases (0,1,2,3,4) ◦ Phase 4 - resting phase (resting membrane potential)  Phase cardiac cells remain in until stimulated  Associated with diastole portion of heart cycle Addition of current into cardiac muscle (stimulation) causes ◦ Phase 0 – opening of fast Na channels and rapid depolarization  Drives Na+ into cell (inward current), changing membrane potential  Transient outward current due to movement of Cl- and K+ ◦ Phase 1 – initial rapid repolarization  Closure of the fast Na+ channels  Phase 0 and 1 together correspond to the R and S waves of the ECG
  4. 4.  Phase 2 - plateau phase ◦ sustained by the balance between the inward movement of Ca+ and outward movement of K + ◦ Has a long duration compared to other nerve and muscle tissue ◦ Normally blocks any premature stimulator signals (other muscle tissue can accept additional stimulation and increase contractility in a summation effect) ◦ Corresponds to ST segment of the ECG. Phase 3 – repolarization ◦ K+ channels remain open, ◦ Allows K+ to build up outside the cell, causing the cell to repolarize ◦ K + channels finally close when membrane potential reaches certain level ◦ Corresponds to T wave on the ECG
  5. 5.  Once an AP is initiated, there is a period (phase 0,1,2, part 3) that a new AP cannot be initiated. Effective or Absolute refractory period (ERP or ARP) Stimulation of cell by adjacent cell depolarizing does not produce new propagated APs Prevents compounded APs from occurring & limits frequency of depolarization and HR
  6. 6.  Fully repolarized -60mv No stable RMP Phase 4: Spontaneous depolarization or pacemaker potential Slow, inward Na+ channels open - "funny" currents Cause the membrane potential to begin to spontaneously depolarize During Ph4 there is also a slow decline in the outward movement of K+
  7. 7.  -50mV T-type CaCh open Ca in: further depolarizes -40 mV L-type CaCh open More Ca in: further depol AP threshold -35mV Phase 0: Depolarization Primarily caused by Ca++ conductance through the L-type Ca++ channels Movement of Ca++ through these is slow so the rate of depolarization (Phase 0 slope) is slower than in other cardiac cells
  8. 8.  Phase 3: Repolarization K+ channels open Increase the outward hyperpolarizing K+ currents At the same time the L- type Ca++ channels close gCa++ decreases Inward depolarizing Ca+ + currents diminish Repolarization
  9. 9.  PCs - Slow, continuous depolarization during rest Continuously moves potential towards threshold for a new action potential (called a phase 4 depolarization)
  10. 10.  SNS - Increased with concurrent inhibition vagal tone:  NA binds to B1 Rec Increases cAMP Increases Ca and Na in Decreases K out Increases slope phase 0 Non-Nodal tissue: More rapid depolarisation More forceful contraction Pacemaker current (If) enhanced  Increase slope phase 4 Pacemaker potential more rapidly reaches threshold Rate increased
  11. 11.  PSNS (Vagal N) Ach binds M2 rec Increases gK+ Decreases inward Ca & Na Pacemaker current (If) suppressed Decreases pacemaker rate Decrease slope of Phase 4 Hyperpolarizes in Phase 4 Longer time to reach threshold voltage
  12. 12.  Restore normal rhythm, rate and conduction or prevent more dangerous arrhythmias1. Alter conduction velocity (SAN or AVN) Alter slope 0 depolarisation or refractoriness2. Alter excitability of cardiac cells by changing duration of ERP (usually via changing APD) ERPinc – Interrupts tachy caused by reentry APDinc – Can precipitate torsades3. Suppress abnormal automaticity
  13. 13.  Block open ACTIVATED Na channels Slow phase 0 depolarisation - upstroke of AP Lengthen APD and ERP. Prolong QRS duration on ECG Anticholinergic S/E. Also blocks K Ch. Greater affinity for rapidly firing channels-exhibit use dependence with intermediate kinetics
  14. 14.  suppresses automaticity in normal Purkinje fibers Little effect on normal sinus node Peripheral vasodilatation may reflexly increase sinus node discharge rate(Anti chol.effect also) Exhibits use dependence and at slower rates exhibit reverse use dependence(on K channels)- TDP Increases ERP of Atria,ventricles,HPS and HV interval
  15. 15.  Suppresses premature SV/V ectopics Conversion and maintainence of atrial flutter/fibrillation into sinus rhythm. Can prevent recurrence of AVNRT
  16. 16.  I.V- 6 to 10 mg/kg at 0.3 to 0.5 mg/kg/min oral— 800 to1000mg-loading Maintainence- 300 to 600q6hr Half life- 5 to 9 hrs
  17. 17.  syncope in 0.5 to 2.0 percent of patients, most often the result of a self-terminating episode of torsades de pointes Significant QT prolongation (QT interval of 500 to 600 milliseconds) is often a characteristic of patients with quinidine syncope most episodes occur within the first 2 to 4 days of therapy, often after conversion of atrial fibrillation to sinus rhythm.
  18. 18.  Magnesium given intravenously (2 gm over 1 to 2 minutes, followed by an infusion of 3 to 20 mg/min) is the initial drug treatment of choice. Atrial or ventricular pacing can be used to suppress the ventricular tachyarrhythmia, perhaps acting by suppressing early afterdepolarizations. Isoproterenol can also be used to increase heart rate
  19. 19.  Least anti cholinergic of class 1 agents Can depress myocardial contractility in high doses
  20. 20.  NAPA elimination half life is 7-8hrs and is excreted only by kidney Procainamide is ecreted both by kidney and liver Renal failure can cause accumulation of NAPA
  21. 21.  SVT-convert AF to sinus In patients with AF and rapid conduction over accessory pathway Can terminate sustained VT better than lidocaine In EPS can be used to stress the his purkinje system in evaluation for pacemaker and also for VT induction.
  22. 22.  IV loading-6 to 13 mg/kg at 0.2 to 0.5 mg/kg/min Maintainence-2 to 6 mg/min Oral loading-500 to 1000 mg Maintainence-250 to 1000 mg q4-6hr Half life-3-5 hrs
  23. 23.  Noncardiac adverse effects from procainamide administration include rashes, myalgias, digital vasculitis, Raynauds phenomenon, Fever and agranulocytosis GI/cns side effects less common Drug induced Lupus developin 20-30% Cardiac-bradycardia,TDP
  24. 24.  Doses are generally 100 to 200 mg orally every 6 hours, with a range of 400 to 1200 mg/day Adverse effects-vagolytic TDP depression of cardiac performance
  25. 25.  Good Na channel block with weak K channel blocking property mean elimination half-life of 13 min in most patients, making it poorly suited to longterm oral use. dose for acute arrhythmia termination is generally 50 mg IV over 1 to 2 minutes
  26. 26.  When administered IV at doses of 50 mg over 3 min, or 10 mg/minute, to a total dose of 1 mg/kg, ajmaline can have the following effects: (1) delta wave disappearance in patients with Wolff- Parkinson-White syndrome (indicating an accessory pathway anterograde effective refractory period more than 250 milliseconds);
  27. 27.  (2) ST-T abnormalities and interventricular conduction blocks in patients with occult chagasic cardiomyopathy (3) heart block in patients with bundle branch block and syncope, but in whom no rhythm disturbance had been discovered (4) right precordial ST elevation in patients with suspected Brugada syndrome in whom the resting electrocardiogram is normal
  28. 28.  Block INACTIVATED Na channels Slow phase 0 depolarisation- Slows upstroke of AP Shorten APD and ERP Ratio ERP/APD is increased Greater affinity for ischaemic tissue that has more inactivated channels, little effect on normal cells – dissociates quickly (0.5sec)
  29. 29.  does not affect normal sinus node automaticity does depress other normal and abnormal forms of automaticity, as well as early and late afterdepolarizations in Purkinje fibers can convert areas of unidirectional block into bidirectional block during ischemia and prevent development of VF by preventing fragmentation of organized large wave fronts into heterogeneous wavelets
  30. 30.  Metabolised in liver ,metabolism inhibited in cardiac failure and half life increased to 4 hrs ,in uncomplicated MI and 10 hrs in cardiogenic shock.
  31. 31.  initial bolus of 1 to 2 mg/kg body weight at a rate of 20 to 50 mg/min, with a second injection of half the initial dose 20 to 40 minutes later transient subtherapeutic plasma concentrations 30 to 120 minutes after initiation of therapy can be countered by giving asecond bolus of 0.5 mg/kg
  32. 32.  To treat arecurtrence arrythmia 6-8 hrs later give another bolus and then increase infusion rate If the initial bolus of lidocaine is ineffective, up to two more boluses of 1 mg/kg may be administered at 5-minute intervals Maintenance infusion rates in the range of 1 to 4 mg/min produce steady-state plasma levels of 1 to 5 mg/ml
  33. 33.  To treat ventricular arrythmias. Not useful for supra ventricular arrythmias dose-related manifestations of central nervous system toxicity: dizziness, paresthesias, confusion, delirium, stupor, coma, and seizures.. Rarely, lidocaine can cause malignant hyperthermia
  34. 34.  can result in severe bradycardia and abnormal sinus node recovery time in patients with sinus node disease rapidly and almost completely absorbed after oral ingestion Elimination half-life is approximately 10 hours
  35. 35.  starting dose is 200 mg orally every 8 hours when rapid arrhythmia control is not essential May be increased or decreased by 50 to 100 mg every 2 to 3 days
  36. 36.  moderately effective antiarrhythmic agent for treating patients with acute and chronic ventricular tachyarrhythmias Mexiletine may be very useful in children with congenital heart disease and serious ventricular arrhythmias Most useful in combination with other agents May be less danngerous in LQTS
  37. 37.  Neurological Cardiac-bradycardia Dose related Therapeutic plasma levels - 0.5 to 2 mg/ml
  38. 38.  In arrythmias caused by digitalis toxicity Prevents delayed after depolarisations 100 mg of phenytoin should be administered intravenously every 5 minutes until the arrhythmia is controlled, 1 gm has been given, or adverse side effects result Orally, phenytoin is given as a loading dose of 1000 mg the first day, 500 mg on the second and third days, and 300 to 400 mg daily thereafter(Half-life24 hrs)
  39. 39.  Block Na channels. Most potent Na channel block Dissociate very slowly (10-20 sec) Strongly depress conduction in myocardium Slow phase 0 depolarisation - upstroke of AP No effect on APD No effect on QRS
  40. 40.  marked drug effects can occur at physiological heart rates Flecainide shortens the duration of the Purkinje fiber action potential but prolongs it in ventricular muscle(heterogenous effects) Conduction time in the atria, ventricles, AV node, and His-Purkinje system is prolonged
  41. 41.  Anterograde and retrograde refractoriness in accessory pathways can increase significantly in a use-dependent fashion Cardiac contractility can be depressed
  42. 42.  starting dose is 100 mg every 12 hours, increased in increments of 50 mg twice daily, no sooner than every 3 to 4 days, until efficacy is achieved, an adverse effect is noted, or to a maximum of 400 mg/day Serum concentration should not exceed 1.0 mg/ml
  43. 43.  ventricular tachyarrhythmias, SVTs, and paroxysmal atrial fibrillation Useful as adiagnostic tool in brugada sybdrome
  44. 44.  marked slowing of conduction precludes its use in patients with second-degree AV block without a pacemaker and warrants cautious administration in patients with ntraventricular conduction disorder Worsening of existing ventricular arrhythmias or onset of new ventricular arrhythmias can occur in 5 to 30 percent of patients
  45. 45.  PROPAFENONE conduction slowing is the major effect depresses sinus node automaticity and A-H, H-V, PR, and QRS intervals increase, as do refractory periods of the atria, ventricles, AV node, and accessory pathways Depreeses ventricular function 150 to 300 mg every 8 hours, not exceeding 1200 mg/day Used for VT,SVT and AF
  46. 46.  dizziness, disturbances in taste, and blurred vision the most common and gastrointestinal side effects next. Exacerbation of bronchospastic lung disease can occur Proarrhythmic responses, which occur more often in patients with a history of sustained VT and decreased ejection fractions
  47. 47.  prolongs AV node and His-Purkinje conduction times and QRS duration. Ventricular refractoriness is prolonged slightly, with no consistent atrial change usual adult dose is 600 to 900 mg/day, given every 8 hours in divided doses, with increments of 150 mg/day at 3- day intervals
  48. 48.  designed as a multicenter, randomized, placebo- controlled trial to test the hypothesis that in patients with prior myocardial infarction, the suppression of ventricular premature depolarizations improves survival free of arrhythmic death
  49. 49.  As data were gathered, it became evident that encainide and flecai nide worsened survival, and these two arms of the trial (called CAST-I) were stopped moricizine arm of the trial was contin ued as CAST-II. But it had to be prematurely terminated as it also worsened survival.
  50. 50.  Role of tachycardia in precipitating arrythmias Increased sympathetic activity in patients with sustained VT Role of C AMP in causation of ischemia related VF Associated anti hypertensive and anti ischemic effects of these drugs
  51. 51.  Hyperpolarisation (if) current-proarrythmic depolarisation in damaged to heart tissue Inward (L type) calcium current indirectly inhibited as level of tissue C AMP falls
  52. 52.  slows spontaneous automaticity in the sinus node or in Purkinje fibers that are being stimulated by adrenergic tone, producing If block block ICa.L stimulated by beta agonists high concentrations of propranolol slow normal automaticity in Purkinje fibers, probably by a direct membrane action Membrane stablising effect cannot be discounted.
  53. 53.  sinus discharge rate in humansdecreases by 10 to 20 percent The PR interval lengthens, as do AV nodal conduction time and AV nodal effective and functional refractory periods (at a constant heart rate), but refractoriness and conduction in the normal His- Purkinje system remain unchanged No effect on ventricular muscle as seen by lack of effect on QRS and QT interval
  54. 54.  Propanolol,sotalol acebutolol approved Metoprolol was tried in arrythmia suppression trials like the one by stienbeck Esmolol with short half life of 9 min can be used in situations where b blockers are otherwise contraindicated.
  55. 55.  Pharmacokinetics:Propranolol is almost 100 percent absorbed, but the effects of first-pass hepatic metabolism reduce bioavailability to about 30 percent and produce significant interpatient variability of plasma concentration for a given dose Beta blockers eliminated by liver have more inpatient variability than those eliminated by liver.
  56. 56.  Arrhythmias associated with thyrotoxicosis, pheochromocytoma, and anesthesia with cyclopropane or halothane or arrhythmias largely related to excessive cardiac adrenergic stimulation, such as those initiated by exercise, emotion, or cocaine.
  57. 57.  Terminate or prevent recurrence of tachycardias like-AVNRT and orthodromic reciprocating tachycardias in the Wolff-Parkinson-White syndrome or inappropriate sinus tachycardia, or for Ats Metoprolol and esmolol may be useful in patients with multifocal AT(bronchospasm is a problem as underlying lung disease is a risk)
  58. 58.  effective for digitalis-induced arrhythmias(watch for AV block) arrhythmias associated with the prolonged QT interval syndrome,MVP,in setting of ischemic heart disease.
  59. 59.  ADVERSE EFFECTS unacceptable hypotension, bradycardia, and congestive heart failure Raynauds,bronchospasm,insomnia,loss of diabetes control,intermittent claudication,vivid dreams,decreased libido, hypoglycemia unawareness.
  60. 60.  CASH EVSEM
  61. 61.  CASH (Randomized Comparison of Antiarrhythmic Drug Therapy With Implantable Defibrillators in Patients Resuscitated From Cardiac Arrest: The Cardiac Arrest Study Hamburg)
  62. 62.  This study was designed to evaluate impact of the ICD vs antiarrhythmic drugs (amiodarone, metoprolol, propafenone), on overall survival rates in survivors of cardiac arrest Number of patients: 288 pts: 99 pts (ICD); 92 pts (amiodarone); 97 pts (metoprolol)
  63. 63.  23% reduction (statistically nonsignificant) in the all-cause mortality rate was seen in the ICD group compared with the amiodarone/metoprolol group. There is a 61% reduction in the sudden death rate in the ICD group compared with the amiodarone/metoprolol group
  64. 64.  Propranolol 0.25 to 0.5 mg q5 min to 0.20 mg/kg Oral-10 to 200 q6- 8hr Time to peak conc.-4 Effective serum conc.-1 to 2.5 Half life--3 to6 hrs
  65. 65.  Esmolol-IV 500µg/min loading dose over 1min Use steps of 50/100/150/200µ/min over 4 min each Half life-9 min Onset-2min Removal of effect within 18-30 min Esmolol is metabolised in RBC without renal/hepatic metabolism
  66. 66.  Block K channels Prolong repolarisation Prolong APD and ERP Useful in Re-Entry tachycardias AMIODARONE (also Class IA, II BB) SOTALOL (also Class II BB)
  67. 67.  Initially developed in the early 1960s as a treatment for angina pectoris, since it produces coronary vasodilation and decreases cardiac oxygen demand Pronounced antiarrhythmic effects redirected its use
  68. 68.  Structural similarities to the thyroid hormones Absorption is limited (30-50%) Metabolised in the liver to produce the active metabolite desethylamiodarone Relatively slow distribution, a steady state of tissue concentrations is reached only after 2 months. Lipophilic nature –large volume of distribution- concentrates in fatty tissue,liver and lung
  69. 69.  elimination half-life after oral long term treatment is 50-60 days 200mg dose-7mg /d of iodine is released Into body(150-200 µg)
  70. 70.  Class-3-acts on K channels-prolongs action potential and prolongs ERP Class-1-blocks inactivated Na channels-more at high heart rates Class-2-non competetive β and α antagonist Class-4- calcium channel blocker.
  71. 71.  slows sinus rate and atrioventricular conduction prolongs the QRS duration ,notably prolongs the QT interval. Abnormal automaticity is inhibited
  72. 72.  Useful for both SVT and VT AF- two trials-canadian trial and DIONOSYS trial showed superior efficacy of amiodarone in decreasing recurrence rate compared to sotalol and dronedarone. Increses refractory period both upperrlobe pulmonary veins Excellent choice for decreasing recurrences in patients with structural heart disease and reduced ejection fraction
  73. 73.  Ventricular arrythmias- Useful in out of hospital VF and refractory VT following cardiac surgery Similar/superior efficacy to lidocaine in cardiac resuscitation Reduces need for and inappropriate shocks in ICD patients-OPTIC trial-superior to sotalol Primary prevention-in patients with reduced EF<35%-decreased arrythmic death without overall effect on mortality
  74. 74.  SCD-HeFT-EF<35%-similar all cause mortality to placebo but higher compared to ICD EMIAT- SCD In post MI with decreased EF- decreased arrythmic deaths ,total deaths remained unchanged CAMIAT-post MI with frequent VPC or nonsustained VT-reduced mortality-SCD and mortality reduced.
  75. 75.  IV- 15 mg/min for 10 min, 1 mg/min for 3 hr, 0.5 mg/min thereafter till 24hrs Maintainence doses-1 mg/min Oral loading- 800 to 1600 qd for 7-14 days maintainence-200 to 600 qd Serum therapeutic level-0.5-1.5 mg% Half life-56 days.
  76. 76.  Increase serum levels-digoxin anticoagulants statins CCBS Tacrolimus Quinidine fentanyl flecainide
  77. 77.  Prevalence of 15% in the first year, increasing up to 50% during long term use. 20 -50% of patients, the drug must be discontinued due to side effects Discontinuation rate was 35% for amiodarone versus 22% for placebo
  78. 78. 200 mg the incidence is 0.1-1.6%, which increases with higher doses 18-24 months after initiation of treatment. dyspnoea, dry cough, weight loss, malaise, low grade fever, and sometimes pain due to Pleuritis earliest abnormality is a decreased carbon monoxide diffusion capacity. Arterial hypoxaemia and restrictive lung function tests Treatment consists of termination of amiodarone and long term use of corticosteroidsEarly diagnosis, mortality is 10% but with late diagnosis or when hospitalisation is necessary, mortality is reported to be as high as 20e33%
  79. 79. Erythematous iscoloration with a b luish shadeDue to prolonged high dose tretment and lipofuscin deposition resolves in 2 yrs of cessation
  80. 80. corneal deposits-excretion in lacrimal fluid Halo vision-necessiate withdrawlOptic neuritis-occurs 4mon -1 yr later warrants withdrawl.
  81. 81.  First licensed for control of severe ventricular arrythmias Non cardio selective water soluble protien bound agent with renal excretion and half life of 12 hours.
  82. 82.  Racemic mixture L-sotalol has class 2 effects-SA and AV node depression D- sotalol has class 3 effects-prolongs APD in atrial ,ventricular refractory periods ,inhibition of conduction in by pass tracts in any direction. D-sotalol showed increased mortality In SWORD study-due to after depolarisations
  83. 83.  Indications-PSVT,WPW, preventing recurrence of AF,ischemic VT, Major trial was EVSEM trial-in decreasing death and arrythmias in patients with EP induced sustained monomorphic VT –better than Class1 agents It is as effective as Flecainide in preventing recurrences of AF and can be used in patients with structural heart disease where flecainide cannot be used. Comparable to amiodarone
  84. 84.  oral dose is 80 to 160 mg every 12 hours, allowing 2 to 3 days between dose adjustments to attain a steady state and to monitor the electrocardiogram for arrhythmias and QT prolongation. Doses exceeding 320 mg/day can be used in patients when the potential benefits outweigh the risk of proarrhythmia.
  85. 85.  Major side effect-torsades de pointes increases to 4 percent in patients with a history of sustained VT and is dose related, reportedly only 1.6 percent at 320 mg/day but 4.4 percent at 480 mg/day
  86. 86.  prolongs repolarization it also activates a slow inward sodium current along with block outward potassium currents, such as Ikr mild slowing of the sinus rate and has minimal effects on AV conduction or QRS
  87. 87.  Given intravenously and has a large volume of distribution. Clearance is renal, with a half-life of 6 hours IV infusion of 1 mg over 10 minutes, second 1-mg dose may be given after the first dose is finished if the arrhythmia persists Watch the patient for atleast 4 hrs in hospital
  88. 88.  termination of an established episode of atrial flutter or fibrillation,but not for short paroxysms or prevention of recurrences. Up to 60 percent of patients with atrial fibrillation and 70 percent of those with atrial flutter convert to sinus rhythm after 2 mg of ibutilide has been administered
  89. 89.  prolongs accessory pathway refractoriness and can temporarily slow the ventricular rate during preexcited atrial fibrillation. Can also terminate episodes of organized atrial tachycardia as well as sustained uniform morphology VT
  90. 90.  Side effects and precautions Torsades is imp. Side effectoccur in approximately 2 percent of patients given the drug (twice as often in women as in men). The adverse effect occurs within the first 4 to 6 hours of dosing, after which the risk is negligible Avoid in patients with QTc>440ms,un stable heart disease,k<4meq/l
  91. 91.  approved for acute conversion of atrial fibrillation to sinus rhythm, as well as chronic suppression of recurrent atrial fibrillation block of the rapid component of the delayed rectifier potassium current (IKr), which is important in repolarization more prominent in the atria than in the ventricles —30 percent increase in atrial refractory period versus 20 percent in the ventricle
  92. 92.  absorbed well, with over 90 percent bioavailability. Fifty to 60 percent of the drug is excreted unchanged in urine, with a mean elimination half- life of 7 to 13 hours Dosing is from 0.125 to 0.5 mg twice daily and must be initiated in a hospital should not be given to patients with a creatinine clearance less than 20 ml/min or a baseline corrected QT interval longer than 440 milliseconds.
  93. 93.  prevention of episodes of supraven-tricular tachyarrhythmias, particularly atrial flutter and fibrillation Chemical cardioversion in AF<6mo More data in favor of cardioversion than maintainence Devoid of negative ionotropic effect hence can be used in patients with decreased EF
  94. 94.  Drugs which increase its concentration are ketoconazole,macrolides,protease inhibitors Additive effect with other drugs that prolong QT interval
  95. 95.  balanced blockade of both rapid and slow components of IK. effect is responsible for the lower rate of proarrhythmia and better preservation of drug efficacy at higher heart rates with this agent compared with pure IKr blockers
  96. 96.  orally once daily, and its absorption is nearly complete and unaffected by food intake once daily at a dosage of 100 to 200 mg. The drug is well tolerated, and dosing need not be adjusted in the presence of renal or hepatic disease likely to be indicated for long-term prevention of atrial flutter and fibrillation.
  97. 97.  Calcium Channel Blockers Bind to L-type Ca channels Vascular SmM, Cardiac nodal & non-nodal cells Decrease firing rate of aberrant PM sites Decrease conduction velocity Prolong repolarisation Especially active at the AVN VERAPAMIL DILTIAZEM
  98. 98.  Narrow complex tachycardias Terminates PSVT/SVT Rate control in AFib/Aflutter NOT WPW or VT or high degree block NOT with BBlockers Negative Inotropy Vasodilation – Hypotension Dose: 5mg IV bolus. Rpt 15 min max 30 mg Diltiazem less adverse effects
  99. 99. • Acts via the adenosine A1 receptor• activation of an outward potassium current (IKADO and IKACH) present in the atrium, sinoatrial and atrioventricular nodes• Activation of the IKADO channel -shortening of the atrial action potential and hyperpolarization of the – depression of sinus node rate and transient AV block• indirect actions via inhibition of intracellular CAMP generation
  100. 100.  In the N region of the AV node, conduction is depressed, along with decreases in action potential amplitude, duration, and V.max. Transient prolongation of the AH interval results, often with transient first-, second-, or third-degree AV node block. Delay in AV nodal conduction is rate dependent. His-Purkinje conduction is generally not directly affected. Adenosine does not affect conduction in normal accessory pathways
  101. 101. • Pharmacokinetics:• Half life-10-30sec• Metabolised by erythrocytes and vascular endothelial cells.• Dose-• 6mg-rapid IV,repeat 2 12 mg doses at 1-2 min intervals if ineffective.• Children-0.0375-0.25mg/kg• Pharmacodynamics- transient (less than 10 seconds) sinus slowing, AV nodal and conduction block
  102. 102.  Interactions: methylxanthines are competitive antagonists, and therapeutic concentrations of theophylline totally block the exogenous adenosine effect. Dipyridamole is a nucleoside transport blocker that blocks reuptake of adenosine, delaying its clearance from the circulation or interstitial space and potentiating its effect.
  103. 103.  AV node and AV reentry Can terminate SA node reentry RVOT VT-inhibition of catecholamine stimulated calcium currents
  104. 104.  Useful in distinction between SVT with aberancy and VT differentiating conduction over the AV node from that over an accessory pathway during ablative procedures designed to interrupt the accessory pathway
  105. 105.  Side effects: most commonly flushing, dyspnea, and chest pressure-lasting less than 1 minute, and are well tolerated. PVCs, transient sinus bradycardia, sinus arrest, and AV block are common when an SVT abruptly terminates. Atrial fibrillation (12 percent )- adenosine administration, perhaps because of the drugs effect in shortening atrial refractoriness-can be problematic in patients with WPW.
  106. 106.  Asthma or h/o asthma 2nd or 3rd degree AV block Sick sinus syndrome
  107. 107.  enhancing both central and peripheral vagal tone actions are largely confined to slowing the sinus node discharge rate, shortening atrial refractoriness, and prolonging AV nodal refractoriness Electrophysiological effects on the His-Purkinje system and ventricular muscle are minimal, except in toxic concentrations
  108. 108.  Serum half-life of digoxin is 36 to 48 hours, and the drug is excreted unchanged by the kidneys Acute Loading dose is 0.5 – 1mg Oral maintainence doses are 0.125-0.25mg Routine monitoring of serum levels not wararnted Quinidine increases concentration of lanoxin
  109. 109.  Mainly for control of ventricular rate in Aflu/Afib In exercise diminution of vagal tone and increase in sympathetic tone overrides the effect of digoxin and patient will experience tachycardia with minimal exertion
  110. 110.  headache, nausea and vomiting, altered color perception, halo vision, and generalized malaise Cardiac –digitalis effect-reverse tick sign ectopic beats of AV junctional or ventricular origin, first-degree AV block, an excessively slow ventricular rate response to atrial fibrillation, or an accelerated AV junctional pacemaker-monitoring
  111. 111.  bradycardias relatedto a markedly enhanced vagal effect (e.g., sinus bradycardia or arrest, AV node block)-withdrawal of digoxin; atropine or temporarypacing
  112. 112.  Tachyarrhythmias-DAD-PAT with varying block, junctional, and fascicular or ventricular tachycardia- Phenytoin can be used for control of atrial tachyarrhythmias lidocaine -treating infranodal tachycardias Potassium administration should be considered for patients with evidence of increased AV junctional or ventricular automaticity Life-threatening arrhythmias can be treated with digoxin-specific antibody fragments Worsening renal function, advanced age, hypokalemia, chronic lung disease, hypothyroidism, and amyloidosis

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