Cardiac Drug Lecture - Jordan Barnett MD


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Lecture given to Paramedics in PA for 2010 updated drug protocols

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Cardiac Drug Lecture - Jordan Barnett MD

  1. 1. A Brief Review of Some ALS Pharmacology<br />Jordan Barnett, MD FACEP FAAEM<br />
  2. 2. The Cardiac Action Potential<br />
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  4. 4. Physiology of cardiac rate and rhythm<br />Cardiac myocytes are electrically excitable<br />Resting intracellular voltage of myocardial cells is negative -90mV (SA node is -40mV)<br />Resting state - K+ inside and Na+ outside cell (Na+/K+ pump)<br />Action potential occurs when Na+ enters the cell and sets up a depolarising current<br />Stimulation of a single muscle fibre causes electrical activity to spread across the myocardium<br />
  5. 5. Phase 1<br />IV<br />Phase 2<br />0 mV<br />III<br />Phase 0<br />I<br />Phase 3<br />-80mV<br />Phase 4<br />II<br />Phases of action potential of cardiac cells<br />Phase 0 rapid depolarisation (inflow of Na+)<br />Phase 1 partial repolarisation (inward Na+ current deactivated, outflow of K+)<br />Phase 2 plateau (slow inward calcium current)<br />Phase 3 repolarisation (calcium current inactivates, K+ outflow)<br />Phase 4 pacemaker potential (Slow Na+ inflow, slowing of K+ outflow) ‘autorhythmicity’<br />Refractory period (phases 1-3)<br />
  6. 6. Phases of The Cardiac Action Potential<br />Class I agents interfere with the sodium channel and are called “Membrane Stabilizing”<br />Class II agents are beta blockers<br />Class III agents affect Potassium efflux<br />Class IV Drugs affect Calcium of the AV NODE<br />Class V agents work by other or unknown Mechanisms.<br />
  7. 7. Vaughan Williams classification of antiarrhythmic drugs<br />Class I: block sodium channels <br />Ia (quinidine, procainamide, disopyramide) AP<br />Ib (lignocaine) AP<br />Ic (flecainide) AP<br />Class II: ß-adrenoceptor antagonists (atenolol, sotalol)<br />Class III: prolong action potential and prolong refractory period (suppress re-entrant rhythms) (amiodarone, sotalol)<br />Class IV: Calcium channel blockers. Impair impulse propagation in nodal and damaged areas (verapamil)<br />Phase 1<br />IV<br />Phase 2<br />0 mV<br />III<br />Phase 0<br />I<br />Phase 3<br />-80mV<br />Phase 4<br />II<br />
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  9. 9. Sinus rhythm<br />Sinoatrial node is cardiac pacemaker<br />Normal sinus rhythm 60-100 beats/min<br />Depolarisation triggers depolarisation of atrial myocardium (‘forest fire’)<br />Conducts more slowly through AV node<br />Conducts rapidly through His bundles and Purkinje fibres<br />
  10. 10. Sinus rhythm<br />Sinoatrial rate controlled by autonomic nervous system<br />Parasympathetic system predominates (M2 muscarinic receptors)<br />Sympathetic system (ß1 receptors)<br />Increased heart rate (positive chronotropic effect)<br />Increased automaticity<br />Facilitation of conduction of AV node<br />
  11. 11. ECG<br />Recording of electrical activity of the heart<br />Net sum of depolarisation and repolarisation potentials of all myocardial cells<br />P-QRS-T pattern<br />P - atrial depolarisation<br />QRS - ventricular depolarisation<br />T - ventricular repolarisation<br />
  12. 12. Review of Class I agents<br />
  13. 13. Review of Class II Agents<br />These are Your Beta Blockers<br />
  14. 14. Class III Agents<br />These Agents Block the potassium channel and prolong repolarization<br />These agents do not affect the Sodium Channel<br />By not affecting the sodium channel, conduction velocity is not affected<br />Prolonging the action potential and refractory period along with maintenance of conduction velocity prevents reentrant arrythmias<br />
  15. 15. Review of Class IV Drugs<br />Calcium blockers which decrease conduction through the av node and shorten the plateau of the cardiac action potential<br />
  16. 16. Class IV agents<br />Reduce contractility of the heart<br />Can be inappropriate in heart failure<br />Allow the body to retain adrenergic control of rate and contractility<br />
  17. 17. Class V Agents<br />Digoxin and Adenosine are examples<br />
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  19. 19. Medication For Review For ALS<br />Cardizem<br />Amiodarone<br />Lidocaine<br />
  20. 20. Amiodarone<br />Indications: Used in a wide variety of atrial and ventricular tachyarrhythmias and for rate control in patients with impaired Left Ventricular function when Digoxin has proven in effective<br />Amiodarone has effects consistent with all of the first four classes of the Vaughan Williams classification of antiarrhythmic agents<br />
  21. 21. History of Amiodarone<br />A Fat Soluble Compound<br />A Brief History <br />Developed in 1961 in Belgium<br />Initially used in Europe to treat Angina<br />Oxford University discovered it has antiarrhythmic properties<br />Argentia first to use for SVT and Ventricular Arrhyttymias<br />1970s used in Europe for life threateiningarrythmias with No approval for FDA – US MDS obtaining it illegally to treat patients via Canada and Europe<br />1980s, approved via pressure from European Pharmaceutical companies<br />
  22. 22. Recommendations for Amiodarone<br />Treatment of shock-refractory VF/Pulseless VT<br />Treatment of Polymorphic VT and wide-complex tachycardia or uncertain origin<br />Control of hemodynamically stable VT when Cardioversion is unsucessful. <br />Used as an adjunct to cardioversion of svt, psvt<br />Acceptable for termination of ectopic or multifocal atrial tachycardia with preserved LV function<br />May be used for rate control in treatment of atrial fibrillation or flutter when other therapies are ineffective<br />
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  27. 27. Who should never get this drug?<br />Hemodynamically unstable VT<br />CARDIOVERT OUT OF THIS RHYTM! NO AMIDOARONE!<br />ALLERGIC REACTION TO COMPOUND<br />Sinus Nodal Bradycardia, AV BLOCK< Second or Third Degree heart Block<br />NEONATES<br />
  28. 28. Actions of Amiodarone<br />Cordarone is classified as a class III antiarrhythmic and prolongs Phase 3 of the cardiac action potential<br />Numerous affects similar to Ia II and IV drugs<br />Primary effect on cardiac tissue (atria, ventricles, SA &AV nodes, His Purkinjes) is to delay repolarization and refractoriness<br />Slows heart by imparing SA nodel function, depressing AV nodal function, modifying the automaticity of spontaneous firing fibers in the purkinje system<br />Prolongs refractory period in Accessory Pathways (WPW Syndrome)<br />
  29. 29. Additional actions of Amiodarone<br />Noncompetitively antagonizes both alpha and beta adrenergic responses to catecholamines<br />
  30. 30. Pharmacokinetics<br />Liver metabolism and eliminated in bile<br />Half life of 28 to 107 days<br />Because of the drug’s slow elimination, stopping the drug when orally used will still allow therapeutic levels for weeks!<br />
  31. 31. Amiodarone<br />Shows beta blocker like actions<br />Potassium Channel blocker like actions on the SA and AV nodes<br />Increases the refractory period via sodium and channel effects<br />Slows intracardiac conduction of the cardiac potential via sodium channel effects<br />Resembles thyroid hormone and it is presumed that binding to the nuclear thyroid receptor might contribute to some of its pharmacologic effects<br />
  32. 32. Precautions<br />Can produce vasodilatation and hypotension<br />May have negative inotropic effects<br />Can prolong the qt<br />
  33. 33. Review of Use in Cardiac Arrest<br />300 mg IV push <br />2000 ACLS Guidleines recommend dilution to 20 to 30 ml D5W<br />Can Consider additional 150 mg IV push in 3 to 5 minutes<br />Maximum cumulative dose: 2.2 G IV /24 hrs<br />ARREST trial showed improved to survival in individuals who suffered cardiac arrest compared to placebo in shock refractory VF<br />
  34. 34. Wide Complex Stable Tachycardia<br />Maximum Cumulative Dose of 2.2 G iv/24 applies<br />Administer Rapid infusion of 150 mg/iv over first 10 minutes. May repeat rapid infusion 150 mg/iv every ten minutes as needed<br />Slow infusion 360 mg iv over 6 hrs (1 mg/min)<br />Maintenance infusion of 540 mg iv over 18 hrs<br />
  35. 35. Is Everyone Still Awake?<br />
  36. 36. Cardizem<br />
  37. 37. Diltiazem<br />Calcium Channel blocker<br />Used to treat Hypertension, angina and some arrhythmias<br />Class IV Antiarrhythmic<br />Vasodilator, increasing blood flow and decreasing heart rate via depression of the AV node’s conduction<br />Negative Inotropic effects, decreases contractility and myocardial oxygen consumption<br />
  38. 38. Diltiazem<br />Decreases the time needed for each heart beat, thereby decreases myocardial oxygen consumption <br />PSVT is converted to NSR by interrupting the reentry circuit in AV nodal tachycardias and WPW<br />
  39. 39. ALS USE of Cardizem<br />Supraventriculartachycardias<br />Atrial Fibrillation or flutter<br />
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  42. 42. ContraindicationsOf Diltiazem<br />Sick Sinus Syndrome<br />Atrioventricular Node Conudction Disturbances<br />Bradycardia<br />Impaired left Ventricular function<br />PVD<br />Prinzmetal’s Angina<br />
  43. 43. Precautions<br />WPW <br />Patients with systolic bps below 90 mm HG<br />Use with betablockers concurrently is dangerous!<br />Can Cause angina, bradycardia, asystole, CHF, AV block, bundle brancy block, PVCs, flushing, Decreased BP, palpitations, Peripheral Edema <br />Can Cause Headaches, dizziness, nausea, constipation, rash, GI disturbances<br />
  44. 44. Useless information about Diltizaem to wake you up!<br />Research shows helps overcome cocaine cravings in drug addicted rats. Believed to be due to calcium blockers on dopaminergicsignalling in the brain<br />Enhances analgesic effect of morphine in test animals without respiratory depression and reduces tolerance<br />Treatment to aid in anal fissures and hemorrhoids as a cream using either vaseline or Phlogel<br />
  45. 45. PharmacoKinetics<br />Liver metabolized<br />70-85% protein bound<br />Metabolite is desacetyldiltiazem with 50% coronary vasodilating activity of Diltiazem<br />
  46. 46. Indications<br />Control of PSVT to NSR<br />Slow ventricular rate in AF or Atrial Flutter<br />Used orally for vasospastic angina<br />Hypertension <br />
  47. 47. Acute Rate Control<br />15 to 20 mg IV over 2 minutes (0.25 mg /kg)<br />May repeat in 15 minutes at 20 to 25 mg over 2 minutes (0.35 mg/kg)<br />Maintenance infusion at 5 to 15 mg/hr, titrated to heart rate (can dilute in D5W or NS)<br />
  48. 48. Lidocaine<br />
  49. 49. Actions<br />Class IB antiarrhythmic<br />Controls Ventricular arrhythmias by blocking fast sodium channels<br />Decreases the slope of phase 4 deploarization and supresses automaticity in the His Purkinje system<br />Acts preferentially on ischemic myocardial tissue with little to no effect on AV nodal or HIS Purkinje Conduction<br />Stabilizes Membranes<br />
  50. 50. PharmacoKinetics<br />Onset is 30 to 90 seconds following IV administration and 10 minutes after IM dose<br />Without an Initial bolus dose, theraputic levels not attained for 30 minutes to several hours<br />Renal Excretion<br />Short half life of 7 to 8 minutes<br />
  51. 51. Indications for Lidocaine<br />Used for suppression of Ventricular arrhythmias and ventricular ectopy (especially long runs of VT)<br />Prophylactic routine use of lidocaine has not been shown to improve mortality following AMI <br />Not to be used to treat chronic PVCS in asymptomatic patient<br />Indicated to control VT and VF refractory to Defibrilation and epinephrine<br />
  52. 52. Dosing and Administration<br />Initial bolus dose of 1 mg /kg followed by additional bolus doses of 0.5 mg/kg q5-10 min as needed to cummulative dose of 3 mg/kg<br />For VF and defibrillation and epi have failed, initial bolus of 1.5 mg/kg is recommended in all patients rapid iv push<br />When IV lines are not available, can be instilled via ET two to two and a half times the iv dose up to total volume of 10 ml<br />
  53. 53. Cardiac Arrest From VF and VT<br />Initial dose 1 to 1.5 mg/kg<br />For refractory vf may give additional 0.5 to 0.75 mg /kg iv puseh, repeat in 5 to 10 minutes to maximum total dose of 3 mg/kg<br />A single dose of 1.5 mg/kg iv in cardiac arrest is acceptable<br />Tracheal administration of 2 to 4 mg/kg<br />
  54. 54. PerfusingArrhytmia<br />Dose Ranges for VT, wide complex tachycardia of uncertain type, significant ectopy is 0.5 to 0.75 mg/kg up to 1 to 1.5 mg/kg iv<br />Rpeat for the above 0.5 to 0.75 mg/kg every 5 to 10 minutes to maximum total of 3 mg /kg<br />
  55. 55. VF and Pulseless VT<br />Treat with IV bolus doses only<br />Maintenance infusions should be started at 2 mg/min and titrated up to 4 mg/min only upon return of perfusion <br />
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  60. 60. Clinical cases<br />
  61. 61. 60 year old man with recurrent blackouts<br />
  62. 62. 54 year woman collapses 24 hours post MI<br />
  63. 63. 76 year old man with breathlessness<br />
  64. 64. 36 year old woman with asthma has ‘thumping in chest’<br />