Antidysrhythmic Medications: Study Guide

• Antidysrhythmics are medications used to treat disturbances in heart rhythm

Requirements for Studying Antidysrhythmics

• Review the Antidysrhythmics presentation on Brightspace
• Review the Ornge Drug Monograph for atropine, epinephrine, dopamine, adenosine, lidocaine, amiodarone, and metoprolol
• Review ALS PCS medical directives for cardiac arrest (medical and traumatic), hypothermia, symptomatic bradycardia, and tachydysrhythmia
• Read articles that cover:
  • Sodium-Channel Blockers (Class I Antiarrhythmics)
  • Beta-Adrenoceptor Antagonists (Beta-Blockers)
  • Potassium-Channel Blockers (Class III Antiarrhythmics)
  • Calcium-Channel Blockers (CCBs)
• Watch videos covering:
  • Arrhythmia Overview - Mechanism of bradyarrhythmia and tachyarrhythmia
  • Pharmacology - ANTIARRHYTHMIC DRUGS (MADE EASY)

Learning Objectives

• Review the cardiac conduction system Cardiac Cycle
• Myocardial depolarization (pacemaker cells vs ventricular myocytes)
• Understand action potential and the cardiac cycle as it relates to ECG parts
• Review dysrhythmia types and their ECG appearance
• Discuss the Vaughan Williams Classification of antidysrhythmics
  • Explain the effect of each class on myocardial action potential
  • Provide a drug example for each class
• Discuss the use of antidysrhythmics in the management of various dysrhythmias
• Review the following medications: Lidocaine, Atropine, Epinephrine, Adenosine, Amiodarone, Dopamine, Metoprolol
• Review the following MDSO's: Medical cardiac arrest (PCP, ACP), traumatic cardiac arrest (PCP, ACP), hypothermia cardiac arrest (PCP, ACP), symptomatic bradycardia (ACP), tachydysrhythmia (ACP)

Cardiac Conduction System

• Conduction starts with the SA node's depolarization
• Depolarization travels through the atria via atrial conduction pathways
• The wave of depolarization hits the AV node, pausing for 0.1 seconds to allow full atrial contraction
• Depolarization goes down the intraventricular septum via the bundle branches
• Ventricular depolarization begins at the apex and goes upwards, conducted through Purkinje fibers

Action Potential

• In a resting cardiac cell, there's a net negative charge inside relative to the outside
• This difference in electronegative charge results from an uneven distribution of ions (sodium, potassium, calcium) across the cell membrane (resting membrane potential)
• An energy-requiring pump, specifically the sodium-potassium ATPase pump, maintains the uneven ion distribution
• A change in ion distribution excites cardiac cells
• Ion movement across the cardiac cell membrane results in an electrical impulse spreading across the cardiac cells
• This electrical impulse leads to myocardial muscle contraction

Cardiac Cycle and ECG

• Atrial depolarization creates the P wave
• The PR segment represents the AV node's delay and impulse propagation through the bundle of HIS
• Depolarization of ventricles creates the QRS complex; atrial repolarization occurs but is overshadowed
• ST segment represents the end of ventricular depolarization
• Repolarization of the ventricles creates the T wave
• The TP segment represents resting state

Dysrhythmias Overview

• Dysrhythmia defined as any deviation from the normal heart rhythm
• Dysrhythmias caused by:
  • Disturbances of Automaticity
  • Change of normal automaticity
  • Induced automaticity
  • Disturbances of Impulse Conduction
  • Atrioventricular Block
  • Reentry

Supraventricular Dysrhythmias

• Originating from the sinus node:
  • Sinus tachycardia (HR>100)
  • Sinus bradycardia (HR<60)
  • Sinus arrhythmia (HR 60-100, irregular)
  • Sick Sinus Syndrome (variable HR)
• Originating in the atria:
  • Premature atrial complex (PAC)
  • Atrial flutter
  • Atrial fibrillation
  • Supraventricular tachycardia
  • Multifocal atrial tachycardia
• Originating at the AV junction
  • Junctional tachycardia
  • Accelerated junctional rhythm
  • Junctional rhythm

AV Blocks

• Can occur with any supraventricular rhythm
• Delayed conduction through the AV node
• Types:
  • First degree AV block
  • Second degree type 1 AV block (Mobitz 1 or Wenckebach)
  • Second degree type 2 AV block (Mobitz 2)
  • Third degree AV block

Ventricular Dysrhythmias

• Premature ventricular contractions (PVC)
• Accelerated idioventricular rhythm
• Idioventricular rhythm
• Ventricular escape rhythm
• Ventricular tachycardia
  • Torsades de pointes
• Ventricular flutter
• Ventricular fibrillation
• Asystole

Paced Rhythms

• Pacing type (Demand, Fixed)
• Chamber paced (Atrial, Ventricular, Atrial and ventricular)

Antidysrhythmics: Overview

• Antidysrhythmic drugs directly/indirectly alter membrane ion conductance, changing cardiac action potentials
• Many tachydysrhythmias are due to re-entry circuits
  • Slowing depolarization, prolonging the effective refractory period, and slowing AV node conduction can break/prevent these
• Excessive sympathetic tone can cause tachydysrhythmia
  • Drugs that block adrenergic stimulation can help reduce sympathetic-induced tachycardia
  • Beta-blockers can also block membrane ion channels, slowing depolarization
• Excessive vagal tone can cause bradydysrhythmias.
  • Drugs that block muscarinic receptors can increase heart rate

Vaughan Williams Classification

• Antidysrhythmics treat/prevent cardiac rhythm disturbances
• The Vaughan Williams Classification System is commonly used to classify antiarrhythmic drugs, based on their predominant electrophysiologic effect on action potential
• With new antiarrhythmic drugs & understanding of drug mechanisms, the classification system breaks down, particularly for Class I and III drugs
  • Many share mechanisms of action with drugs in other classes
• Class 1: Sodium channel blocker
• Class 2: Beta-blocker
• Class 3: Potassium channel blocker
• Class 4: Calcium channel blocker

Class 1A: Sodium Channel Blockers

• Medication example: Procainamide
• Indications include Supraventricular and ventricular dysrhythmias such as SVT (AVNRT and WPW), atrial flutter, atrial fibrillation, sustained ventricular tachycardia
• Effects include decreased myocardial excitability, slowed conduction velocity, and reduced myocardial contractility
• The mechanism of action involves prolonging the QRS and QT intervals by blocking the rapid potassium outward current and effective refractory period (ERP) Slowed repolarization occurs
• Reduce the rate and magnitude of depolarization by blocking sodium channels in their open state which leads to a decrease in conduction velocity in non-nodal tissue
• Na-channel blockade is cumulative, meaning that blockade increases with each heartbeat
• Adverse, it can cause hypotension, bradycardia, atrioventricular block, and ventricular tachycardia

Class 1B: Sodium channel blockers

• Medication: Lidocaine
• Use: Short term therapy for ventricular dysrhythmias, and is not effective against supraventricular arrhythmias
• Effects: Suppresses excitability in ischemic, depolarized tissue, and at high ventricular rates
• Mechanism:
  • Little effect on the QRS of normal heartbeats at normal heart rates, and slightly shortens the QT
  • Primary effects are due to blockade in the inactive state
  • Significantly increase the ERP in ischemic tissue Adverse effects can include hypotension, bradycardia, dizziness, respiratory depression, drowsiness, vomiting

Class 1C – Sodium Channel Blockers

• Medications include Flecainide, propafenone
• Use: Maintenance therapy for supraventricular dysrhythmias in patients without heart disease
• QRS is markedly prolonged at normal heart rates and rhythms
• Large block of open Na channels and very slow unbinding during diastole
• Selective, marked depression of excitability of depolarized (ischemic) tissue
• Minimal effect on ERP
• Torsades de Pointes can cause increased risk of sudden death in patients with a prior history of myocardial infarction or sustained ventricular arrhythmias

Class 2 – Beta Blockers

• Medications include Propranolol, metoprolol, esmolol, acebutolol
• Prevent/terminate tachyarrhythmias caused by increased sympathetic tone, catecholamines, or tissue super-sensitivity
• Effects include Decreased automaticity of ectopic pacemakers (less arrhythmogenesis), prolonged refractory period, decrease in ventricular fibrillation threshold and reversal of ischemia/reperfusion
• Beta-blockers bind to beta-adrenoceptors, blocking norepinephrine and epinephrine
• Some beta-blockers possess membrane stabilizing activity (MSA)
• Can cause Bradycardia, hypotension, hypoglycemia, bronchoconstriction

Class 3 – Potassium Channel Blockers

• Medications; Amiodarone, sotalol, bretylium

• Suppress tachyarrhythmias caused by reentry mechanisms Amiodarone is used in recurrent ventricular fibrillation, hemodynamically unstable ventricular tachycardia, shock-resistant ventricular fibrillation, atrial fibrillation and AV nodal re-entrant tachycardia

• Sotalol is used maintain normal sinus rhythm in patient with highly symptomatic atrial fibrillation/flutter who are currently in sinus rhythm

• Mechanism: Increases QT interval by blocking potassium channels which result in prolongation of repolarization

• TdP can result

• Due to Class IV effects, amiodarone is contraindicated in patients with heart block, or sinoatrial node dysfunction

Amiodarone

• Indications include Recurrent/refractory VF and hemodynamically unstable VT + Acute control of SVT/PSVT, including recent-onset atrial fibrillation
• Mechanism of action includes blockage of Na, K, and Ca channels, as well as α- and β-adrenergic receptors
• Contraindications include Severe SA node disease + Heart block, bradycardia with associated syncope, except in patients with a functioning artificial pacemaker + Prolonged QT
• Adverse effects include Pulmonary fibrosis + Hypothyroidism + Bradycardia, AV block + Hypotension and Heart failure

Class 4 – Calcium Channel Blockers

• Medication: Diltiazem, verapamil
• Slow ventricular response to atrial fibrillation/flutter, terminate and prevent SVT
• In cardiac nodal tissue, CCBs block L-type calcium channels causing a slow AV node conduction and increased the AV node ERP
• May cause Excessive bradycardia, atrioventricular nodal block, and depressed contractility

Other Antidysrhythmics - Adenosine

• Used in the treatment of re-entry circuit SVT/WPW to find unknown origin
• Decreases heart rate and reduces conduction velocity, especially at the AV node, which can produce atrioventricular block
• Stimulates adenosine A1 receptors in the SA and AV node, causing decreased inward Ca and inward Na through funny sodium channels
• May cause Dyspnea, angina, nausea, impending sense of doom, hypotension, and heart block.

Adenosine

• Indications for the conversion of paroxysmal supraventricular tachycardia to sinus rhythm to aid in diagnosis of SVT
• Slows conduction through the AV node, interrupts AV-nodal re-entry pathways and normal rhythm in PSVT
• Contraindications include Second- or third-degree AV block, bronchoconstrictive/bronchospastic lung disease, and asthma
• Side effects are transient asystole, varied atrial and ventricular arrhythmias and facial flushing, chest pain, dyspnea, headache, light-headedness

Medical Cardiac Arrest

• Shockable rhythms include pulseless VT and VF
  • Treated through defibrillation, epinephrine, lidocaine, or amiodarone
• Non Shockable rhythms include PEA and/asystole
  • Treated by addressing underlying causes and administering epinephrine
• Special Cases
  • Hyperkalemia Arrest which includes calcium and epinephrine
  • Polymorphic VT, which includes magnesium

VT With Pulse

• Monomorphic VT:
  • HR>150
  • if hemodynamically stable, administer lidocaine or amiodarone + Synchronized cardioversion + Treat underlying causes
• Polymorphic VT:
  • Consider toxicology
  • Use Magnesium, calcium, sodium bicarbonate, if not, use Defibrillation/cardioversion

Symptomatic Bradycardia

• Address underlying causes such as toxicology
• With high junctional rhythms with 2nd: degree type 1 AV blocks, give Atropine and if not working, use Epinephrine, dopamine, or isoproterenol + consider TCP/TVP
• With low junctional rhythms, 2nd degree type 2, 3rd degree AV blocks, or idioventricular rhythms, use Epinephrine, dopamine, or isoproterenol + consider TCP/TVP

Symptomatic Atrial Fibrillation/Flutter

- Determine anticoagulation and hemodynamic status.
- Use Amiodarone or procainamide to control the underlying causes
- Beta blockers or calcium channel blockers can benefit
- If dire, apply Synchronized cardioversion

PSVT

• Consider Hemodynamic status
• Determine the underlying causes and apply Valsalva manoeuvres
• use Adenosine or diltiazem
• If unsuccessful, apply Synchronized cardioversion

Other Dysrhythmias

• Sinus tachycardia:
  • Treat underlying causes
• Premature complexes (PAC, PJC, PVC):
  • Treat underlying causes
  • Administer amiodarone or lidocaine
• Atrial and junctional tachycardia:
  • Treat underlying causes
  • Use Amiodarone, diltiazem (atrial), or beta blockers