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Agents for Cardiac Arrhythmias.pdf
- 1. Agents for Cardiac Arrhythmias CHRISTINE JOY MEDIDA , RPH
- 2. Anatomy and Physiology of the Heart THE STEPS IN HEART CONDUCTION
- 4. HEART CONDUCTION Step 1: Pacemaker Impulse Generation
- 5. HEART CONDUCTION Step 2: AV Node Impulse Conduction
- 6. HEART CONDUCTION Step 3: AV Bundle Impulse Conduction
- 7. HEART CONDUCTION Step 4: Purkinje Fibers Impulse Conduction
- 13. ECG The body surface manifestation of the depolarization and repolarization waves of the heart
- 14. Normal ECG
- 17. Arrhythmia ❑ Normal heartbeat for adult: 60-100 bpm ❑ Irregular heartbeat ▪ Tachycardia: too fast (150-220 bpm) ▪ Bradycardia: too slow (<40 bpm) ▪ Premature contraction: too early ▪ Fibrillation: too irregular
- 18. Factors that trigger arrhythmia ❑Ischemia ❑Hypoxia ❑Acidosis or Alkalosis ❑Electrolyte Abnormalities ❑Excessive cathecolamine exposure ❑Autonomic influences ❑Drug toxicity (E.g. Digitalis) ❑Overstretching of cardiac fibers ❑Presence of scarred/diseased tissues
- 19. Factors that trigger arrhythmia ❑Ischemia ❑Hypoxia ❑Acidosis or Alkalosis ❑Electrolyte Abnormalities ❑Excessive cathecolamine exposure ❑Autonomic influences ❑Drug toxicity (E.g. Digitalis) ❑Overstretching of cardiac fibers ❑Presence of scarred/diseased tissues
- 20. Causes of Arrhythmia Abnormal automaticity Disturbances in impulse conduction
- 21. Abnormal Automaticity Hypokalemia Beta-Adrenoceptor Stimulation Positive Chronotropic Drugs Fiber Stretch Acidosis
- 22. Disturbances in Impulse Conduction AV nodal block Bundle Branch Block
- 23. REENTRY or "Circus Movement"
- 24. 3 Conditions Presence of obstacle (anatomic or physiologic) Unidirectional block at some point in the circuit; conduction must die out in one direction
- 25. Conduction time around the circuit must be long enough that the retrograde impulse does not enter refractory tissue as it travels around the obstacle
- 26. ATRIAL FIBRILLATION no visible P waves irregular R-R intervals
- 27. Problems: Anxiety Palpitations Risk of failure symptoms Risk of cardiac thrombus & embolism (stroke)
- 28. Supraventricular Tachycardia (SVT) Heart rate ≥ 180 bpm
- 30. Polymorphic - Ex: Torsades de Pointes
- 31. Basic Pharmacology of the Antiarrhythmic Agents
- 32. Aim of Therapy To reduce ectopic pacemaker activity or modify conduction or refractoriness in reentry circuits to disable circus movement
- 33. Major Mechanism of Action • Sodium channel blockade • Blockade of sympathetic autonomic effects in the heart • Prolongation of the effective refractory period (Potassium Channel Blocker) • Calcium Channel blockade
- 34. Major Mechanism of Action • Sodium channel blockade • Blockade of sympathetic autonomic effects in the heart • Prolongation of the effective refractory period (Potassium Channel Blocker) • Calcium Channel blockade
- 35. Major Mechanism of Action • Sodium channel blockade • Blockade of sympathetic autonomic effects in the heart • Prolongation of the effective refractory period (Potassium Channel Blocker) • Calcium Channel blockade
- 36. Major Mechanism of Action • Sodium channel blockade • Blockade of sympathetic autonomic effects in the heart • Prolongation of the effective refractory period (Potassium Channel Blocker) • Calcium Channel blockade
- 38. Sodium Channel Blockers ◦ Class Ia ◦ Class Ib ◦ Class Ic
- 39. Class IA (moderate) prolongs action potential (1-10 seconds) ▪Procainamide ▪Quinidine ▪Disopyramide
- 40. 1) PROCAINAMIDE ▪ slows conduction velocity and pacemaker rate ▪ prolongs action potential duration and dissociates from sodium channel with intermediate kinetics ▪ direct depressant effects on SA and AV nodes
- 41. Clinical Applications ▪ Most atrial and ventricular arrhythmias ▪ Second line drug for most sustained ventricular arrhythmias associated with acute MI
- 42. Toxicity ▪ Hypotension ▪ QT interval prolongation ▪ Induction of Torsade de pointes ▪ Long term therapy produces reversible lupus-related symptoms
- 43. 2) QUINIDINE similar to Procainamide but more toxic
- 44. Toxicity ▪ Torsade de Pointes ▪ Cinchonism (headache, dizziness and tinnitus)
- 45. Torsades de Pointes ▪is an uncommon and distinctive form of polymorphic ventricular tachycardia (VT) characterized by a gradual change in the amplitude and twisting of the QRS complexes around the isoelectric line.
- 47. 3) DISOPYRAMIDE ▪similar to procainamide but significant antimuscarinic effects; may precipitate heart failure
- 48. Adverse Effect ▪Urinary retention ▪Dry mouth ▪Blurred Vision ▪Constipation ▪Worsening of Preexisting Glaucoma
- 49. Class IB (weak) shortens action potential (<1 second) ▪Lidocaine ▪Phenytoin ▪Tocainide ▪Mexiletine
- 50. 1) LIDOCAINE ▪Xylocaine® ▪has a low incidence of toxicity and a high degree of effectiveness in arrhythmias associated with myocardial infarction ▪given IV
- 51. Clinical Applications ▪ Terminate ventricular tachycardia ▪ Prevent ventricular fibrillation after cardioversion
- 53. Toxicity ▪ Neurologic symptoms: ▪ Nsytagmus ▪ Paresthesia ▪ Tremor ▪ nausea of central origin ▪ Lightheadedness ▪ hearing disturbances ▪ slurred speech and convulsion
- 54. 2) MEXILETINE ▪Mexitil® ▪an orally active congener of Lidocaine
- 55. Clinical Applications ▪ same with Lidocaine ▪ has significant efficacy in relieving chronic pain, especially pain due to diabetic neuropathy & nerve injury (off-label)
- 57. Class IC (strong) no effect on AP (>10 seconds) ▪Flecainide ▪Encainide ▪Moricizine ▪Propafenone
- 58. 1) FLECAINIDE ▪ Tambocor® ▪ a potent blocker of sodium and potassium channels with slow unblocking kinetics
- 59. Clinical Applications ▪Supraventricular Arrhythmias in patient with normal heart ▪DO NOT use in ischemic conditions (Post- Myocardial Infarction)
- 61. 2) PROPAFENONE ▪ Rhythmol® ▪ Used primarily for supraventricular arrhythmias ▪ ADR: ▪ metallic taste ▪ Constipation ▪ arrhythmia exacerbation
- 62. 3) MORICIZINE ▪ an antiarrhythmic phenothiazine derivative that was used for treatment of ventricular arrythmias
- 64. Clinical Applications ▪ Atrial arrhythmias and prevention of recurrent infarction and sudden death
- 65. Toxicity ▪ Asthma ▪ AV Blockade ▪ Acute Heart Failure
- 66. 1) Propanolol (Inderal®) 2) Esmolol (Brevibloc®) - ✓ a short acting β-blocker used primarily as an antiarrhythmic drug for intraoperative and other acute arrhythmiass 3) Sotalol ✓ a non-selective β-blocking drug that prolongs the action potential
- 68. CLASS III ▪ Drugs that prolong effective refractory period by prolonging the action potential ▪ Potassium Channel Blockers
- 70. 1) AMIODARONE ▪Cordarone® ▪given IV or PO
- 71. Clinical Applications ▪Serious ventricular arrhythmias and supraventricular arrhythmias
- 72. Toxicity ▪ Bradycardia ▪ Heart block in diseased heart ▪ Peripheral vasodilation ▪ Pulmonary & hepatic toxicity ▪ Hyper- or Hypothyroidism
- 73. ▪ Photodermatitis ▪ Gray-blue discoloration in exposed areas of the skin ▪ Asymptomatic corneal microdeposits
- 75. Other possible effects ▪ blocks the peripheral conversion of thyroxine (T4) and triiodothyronine (T3) ▪ a potential source of large amount of inorganic iodine
- 76. 2) DRONEDARONE ▪ a structural analog of Amiodarone but lacks iodine atoms ▪ the first antiarrhythmic drug to demonstrate a reduction in mortality or hospitalization in patients with atrial fibrillation
- 77. 3) VERNAKALANT ▪ an investigational multi-channel blocker that was developed for the treatment of atrial fibrillation
- 78. Toxicity ▪Dysgeusia (disturbance of taste) ▪Sneezing ▪Paresthesia ▪Cough ▪Hypotension
- 79. 4) SOTALOL ▪ Betapace® ▪ has both β-adrenergic blocking (Class II) and action potential prolonging actions (Class III)
- 80. 5) DOFETILIDE ▪ Tikosyn® ▪ approved for the maintenance of normal sinus rhythm in patients with atrial fibrillation ▪ S/E: Torsades de pointes
- 81. 6) IBUTILIDE ▪ Corvert® ▪ IV is used for the acute conversion of atrial flutter and atrial fibrillation to normal sinus rhythm ▪ S/E: Torsade de pointes, QT interval prolongation
- 82. Calcium Channel Blocking drugs
- 83. CLASS IV ▪ Calcium Channel Blocking drugs ▪ Verapamil - prototype ▪ first introduced as antianginal agents ▪ Dihydropyridines do not share antiarrhythmic efficacy and may precipitate arrhythmias.
- 84. 1) VERAPAMIL ▪ Isoptin® ▪ blocks both activated and inactivated L-type calcium channel
- 85. Effects ▪ slows SA node automaticity and AV nodal conduction velocity ▪ decreases cardiac contractility ▪ reduces blood pressure
- 86. Clinical Application ▪ Supraventricular tachycardia
- 87. 2) DILTIAZEM ▪ Cardizem® ▪ appears to be similar in efficacy to verapamil in the management of supraventricular arrhythmias, including rate control in atrial fibrillation
- 90. 1) DIGOXIN ▪ MOA: inhibits Na+/K+-ATPase ▪ Uses: ▪ 1-2 ng/mL (for atrial fibrillation or flutter) ▪ 0.5-0.8 ng/mL (for systolic heart failure)
- 91. 2) ADENOSINE ▪ Adenocard® ▪ a nucleoside that occurs naturally throughout the body ▪ half-life: < 10 seconds
- 92. Mechanism of Action ▪ activation inward rectifier K+ current and inhibition of Ca2+ current
- 93. Clinical Application ▪ Currently the DOC for paroxysmal supraventricular tachycardia
- 94. Toxicity ▪ flushing ▪ chest tightness ▪ dizziness
- 95. 3) MAGNESIUM ▪ MOA: poorly understood; interacts with Na+/K+ ATPase, K+ and Ca2+ channels
- 96. Clinical Applications ▪Torsade de pointes ▪Digitalis-induced arrhythmias
- 97. Toxicity ▪ Muscle weakness in overdose
- 98. 4) POTASSIUM ▪ MOA: increases K+ permeability, K+ current
- 99. Effects of Increasing K+ Serum ▪ a resting potential depolarizing action ▪ a membrane potential stabilizing action ▪ slows ectopic pacemakers ▪ slows conduction velocity in heart
- 100. Clinical Applications ▪ Digitalis-induced arrhythmias ▪ Arrhythmias associated with hypokalemia
- 101. Toxicity ▪ Reentrant arrhythmias ▪ Fibrillation ▪ Arrest in overdose