Agents Used in Cardiac Arrhythmias Chapter 20 PDF

Agents Used in Cardiac Arrhythmias Chapter 20 Heart Conduction  Step 1: Pacemaker Impulse Generation Step 2 : AV Node Impulse Conduction Step 3: AV Bundle Impulse Conduction Step 4: Purkinje Fibers Impulse Conduction Action Potential Phases 0 = Upstroke/Depolari...

Agents Used in Cardiac Arrhythmias Chapter 20 Heart Conduction  Step 1: Pacemaker Impulse Generation Step 2 : AV Node Impulse Conduction Step 3: AV Bundle Impulse Conduction Step 4: Purkinje Fibers Impulse Conduction Action Potential Phases 0 = Upstroke/Depolarization 1 = Early Fast Repolarization 2 = Plateau 3 = Repolarization 4 = Diastole ECG the body surface manifestation of the depolarization and repolarization waves of the heart Normal ECG P wave generated by atrial depolarization QRS wave generated by ventricular muscle depolarization T wave generated by ventricular repolarization ARRHYTHMIA also called dysrrhythmia an irregular heartbeat - the heart may beat too fast (tachycardia), too slowly (bradycardia), too early (premature contraction) or too irregularly (fibrillation). Factors that trigger arrhythmia Ischemia Hypoxia Acidosis or Alkalosis Electrolyte Abnormalities Execessive cathecolamine exposure Autonomic influences Drug toxicity (E.g. Digitalis) Overstretching of cardiac fibers Presence of scarred/diseased tissues Causes of Arrhythmia Abnormal automaticity Disturbances in impulse conduction Abnormal Automaticity Hypokalemia Beta-Adrenoceptor Stimulation Positive Chronotropic Drugs Fiber Stretch Acidosis Disturbances in Impulse Conduction AV nodal block Bundle Branch Block REENTRY or "Circus Movement" 3 Conditions Presence of obstacle (anatomic or physiologic) Unidirectional block at some point in the circuit; conduction must die out in one direction  Conduction time around the circuit must be long enough that the retrograde impulse does not enter refractory tissue as it travels around the obstacle ATRIAL FIBRILLATION no visible P waves irregular R-R intervals Problems: Anxiety Palpitations Risk of failure symptoms Risk of cardiac thrombus & embolism (stroke) Supraventricular Tachycardia Heart rate ≥ 180 bpm Ventricular Tachycardia Monomorphic  Polymorphic - Ex: Torsades de Pointes Basic Pharmacology of the Antiarrhythmic Agents Aim of Therapy To reduce ectopic pacemaker activity or modify conduction or refractoriness in reentry circuits to disable circus movement Major Mechanism of Action Sodium channel blockade Blockade of sympathetic autonomic effects in the heart Prolongation of the effective refractory period Calcium Channel blockade  SPECIFIC ANTIARRHYTHMIC AGENTS Class I Sodium Channel Blockers Class IA prolongs action potential Ex: Procainamide Quinidine Disopyramide PROCAINAMIDE Effects: 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 Clinical Applications Most atrial and ventricular arrhythmias Second line drug for most sustained ventricular arrhythmias associated with acute MI Toxicity Hypotension QT interval prolongation Induction of Torsade de pointes Long term therapy produces reversible lupus-related symptoms QUINIDINE similar to Procainamide but more toxic Toxicity Torsade de Pointes Cinchonism (headache, dizziness and tinnitus) 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. DISOPYRAMIDE similar to procainamide but significant antimuscarinic effects; may precipitate heart failure Adverse Effect Urinary retention Dry mouth Blurred Vision Constipation Worsening of Preexisting Glaucoma Class IB shortens action potential Ex: Lidocaine Phenytoin Tocainide Mexiletine LIDOCAINE Xylocaine® has a low incidence of toxicity and a high degree of effectiveness in arrhythmias associated with myocardial infarction given IV Clinical Applications Terminate ventricular tachycardia Prevent ventricular fibrillation after cardioversion Toxicity Neurologic symptoms: Nsytagmus, paresthesia, tremor, nausea of central origin, lightheadedness, hearing disturbances, slurred speech and convulsion MEXILETINE Mexitil® an orally active congener of Lidocaine Clinical Applications same with Lidocaine has significant efficacy in relieving chronic pain, especially pain due to diabetic neuropathy & nerve injury (off-label) Toxicity Neurologic: Tremor, blurred vision, lethargy Class IC no effect on AP Ex: Flecainide Encainide Moricizine Propafenone FLECAINIDE Tambocor® a potent blocker of sodium and potassium channels with slow unblocking kinetics Clinical Applications Supraventricular Arrhythmias in patient with normal heart DO NOT use in ischemic conditions (Post-Myocardial Infarction) Toxicity Proarrhythmic PROPAFENONE Rhythmol® Used primarily for supraventricular arrhythmias ADR: metallic taste, constipation, arrhythmia exacerbation MORICIZINE an antiarrhythmic phenothiazine derivative that was used for treatment of ventricular arrythmias CLASS II Beta-Adrenoceptor Blocking Agents Clinical Applications Atrial arrhythmias and prevention of recurrent infarction and sudden death Toxicity Asthma AV Blockade Acute Heart Failure  Propanolol (Inderal®) Esmolol (Brevibloc®) - a short acting β-blocker used primarily as an antiarrhythmic drug for intraoperative and other acute arrhythmiass Sotalol - a non-selective β-blocking drug that prolongs the action potential CLASS III Drugs that prolong effective refractory period by prolonging the action potential Potassium Channel Blockers  Amiodarone Sotalol Bretylium Dofetilide Ibutilide AMIODARONE Cordarone given IV or PO Clinical Applications Serious ventricular arrhythmias and supraventricular arrhythmias Toxicity Bradycardia Heart block in diseased heart Peripheral vasodilation Pulmonary & hepatic toxicity Hyper- or Hypothyroidism  Photodermatitis Gray-blue discoloration in exposed areas of the skin Asymptomatic corneal microdeposits  blocks the peripheral convertion of thyroxine (T4) and triiodothyronine (T3) a potential source of large amount of inorganic iodine 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 VERNAKALANT an investigational multi- channel blocker that was developed for the treatment of atrial fibrillation Toxicity Dysgeusia (disturbance of taste) Sneezing Paresthesia Cough Hypotension SOTALOL Betapace® has both β-adrenergic blocking (Class II) and action potential prolonging actions (Class III) DOFETILIDE Tikosyn approved for the maintenance of normal sinus rhythm in patients with atrial fibrillation S/E: Torsades de pointes 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 CLASS IV Calcium Channel Blocking drugs Verapamil - prototype – first introduced as antianginal agents Dihydropyridines do not share antiarrhythmic efficacy and may precipitate arrhythmias. VERAPAMIL Isoptin® blocks both activated and inactivated L-type calcium channel Effects slows SA node automaticity and AV nodal conduction velocity decreases cardiac contractility reduces blood pressure Clinical Application Supraventricular tachycardia DILTIAZEM Cardizem® appears to be similar in efficacy to verapamil in the management of supraventricular arrhythmias, including rate control in atrial fibrillation  Miscellaneous Antiarrhythmic Agents 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) ADENOSINE Adenocard® a nucleoside that occurs naturally throughout the body half-life: < 10 seconds Mechanism of Action activation of inward rectifier K+ current and inhibition of Ca2+ current Clinical Application Currently the DOC for paroxysmal supraventricular tachycardia Toxicity flushing chest tightness dizziness MAGNESIUM MOA: poorly understood; interacts with Na+/K+ ATPase, + 2+ K and Ca channels Clinical Applications Torsade de pointes Digitalis-induced arrhythmias Toxicity Muscle weakness in overdose POTASSIUM MOA: increases K+ permeability, K+ current Effects of Increasing K+ Serum a resting potential depolarizing action a membrane potential stabilizing action  slows ectopic pacemakers slows conduction velocity in heart Clinical Applications Digitalis-induced arrhythmias Arrhythmias associated with hypokalemia Toxicity Reentrant arrhythmias Fibrillation Arrest in overdose