Heart Conduction and ECG Basics

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Questions and Answers

What is the mechanism of action of digoxin?

  • Blocks both activated and inactivated L-type calcium channels
  • Inhibits Ca2+ channels
  • Activates inward rectifier K+ current
  • Inhibits Na+/K+-ATPase (correct)

Which antiarrhythmic agent is the drug of choice for paroxysmal supraventricular tachycardia?

  • Magnesium
  • Verapamil
  • Diltiazem
  • Adenosine (correct)

What effect does verapamil have on the heart?

  • Increases blood pressure
  • Increases cardiac contractility
  • Slows SA node automaticity (correct)
  • Enhances AV nodal conduction velocity

What is a possible toxicity associated with potassium administration?

<p>Reentrant arrhythmias (D)</p> Signup and view all the answers

What clinical condition is magnesium commonly used to treat?

<p>Torsade de pointes (A)</p> Signup and view all the answers

What is characterized by the absence of visible P waves and irregular R-R intervals?

<p>Atrial Fibrillation (C)</p> Signup and view all the answers

What condition results from the interaction of three specific criteria involving conduction and obstacles?

<p>Reentry Circuit (A)</p> Signup and view all the answers

Which class of antiarrhythmic drugs primarily works by sodium channel blockade?

<p>Class I (B)</p> Signup and view all the answers

Which of the following is not a common trigger for arrhythmia?

<p>Hyperglycemia (A)</p> Signup and view all the answers

What is the primary effect of Procainamide?

<p>Slows conduction velocity (A)</p> Signup and view all the answers

Which of the following is a side effect of Quinidine?

<p>Cinchonism (D)</p> Signup and view all the answers

What type of tachycardia is defined as having a heart rate of 180 bpm or more?

<p>Supraventricular Tachycardia (B)</p> Signup and view all the answers

What is the pharmacological aim when treating arrhythmias?

<p>To reduce ectopic pacemaker activity (B)</p> Signup and view all the answers

Which arrhythmia is characterized by a gradual change in the amplitude and twisting of the QRS complexes?

<p>Torsades de Pointes (C)</p> Signup and view all the answers

What is the significance of calcium channel blockade in antiarrhythmic therapy?

<p>Decreases automaticity (A)</p> Signup and view all the answers

Which adverse effect is associated with disopyramide?

<p>Urinary retention (D)</p> Signup and view all the answers

What is a characteristic of class IB antiarrhythmic agents?

<p>They shorten the action potential. (C)</p> Signup and view all the answers

Which class of antiarrhythmic drugs is primarily used for atrial arrhythmias?

<p>Class II (B)</p> Signup and view all the answers

What is the mechanism of toxicity in Flecainide?

<p>Proarrhythmic effects (D)</p> Signup and view all the answers

Which statement about Amiodarone is false?

<p>It primarily treats supraventricular arrhythmias. (D)</p> Signup and view all the answers

What effect does Dronedarone lack compared to Amiodarone?

<p>Iodine atoms (B)</p> Signup and view all the answers

Which antiarrhythmic drug is indicated for the maintenance of normal sinus rhythm in atrial fibrillation?

<p>Dofetilide (B)</p> Signup and view all the answers

Which class of drugs does Verapamil belong to?

<p>Class IV (D)</p> Signup and view all the answers

What is a common side effect of Sotalol?

<p>Torsades de pointes (C)</p> Signup and view all the answers

Which antiarrhythmic drug is effective in relieving chronic pain due to diabetic neuropathy?

<p>Mexiletine (D)</p> Signup and view all the answers

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Study Notes

Heart Conduction

  • Heart conduction involves four steps
    • Pacemaker impulse generation
    • AV node impulse conduction
    • AV bundle impulse conduction
    • Purkinje fibers impulse conduction

Action Potential Phases

  • 0 = Upstroke/Depolarization
  • 1 = Early Fast Repolarization
  • 2 = Plateau
  • 3 = Repolarization
  • 4 = Diastole

ECG

  • The ECG reflects 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 known as dysrrhythmia
  • Describes irregular heartbeats
    • Tachycardia: heart beats too fast
    • Bradycardia: heart beats too slowly
    • Premature contraction: heart beats too early
    • Fibrillation: heart beats irregularly

Factors that trigger arrhythmia

  • Ischemia
  • Hypoxia
  • Acidosis or Alkalosis
  • Electrolyte Abnormalities
  • Excessive catecholamine 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"

  • Requires three 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 (AFib)

  • No visible P waves
  • Irregular R-R intervals

Problems with AFib

  • Anxiety
  • Palpitations
  • Risk of heart failure symptoms
  • Risk of cardiac thrombus & embolism (stroke)

Supraventricular Tachycardia (SVT)

  • Heart rate ≥ 180 bpm

Ventricular Tachycardia (VT)

  • Monomorphic
  • Polymorphic (e.g., Torsades de Pointes)

Basic Pharmacology of Antiarrhythmic Agents

Aim of Therapy

  • Reduce ectopic pacemaker activity
  • Modify conduction or refractoriness in reentry circuits to disable "circus movement"

Major Mechanisms 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 the action potential
    • Procainamide
    • Quinidine
    • Disopyramide
Procainamide
  • Slows conduction velocity and pacemaker rate
  • Prolongs action potential duration
  • 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
Procainamide 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
Quinidine Toxicity
  • Torsade de Pointes
  • Cinchonism (headache, dizziness, and tinnitus)

Class IB

  • Shortens action potential
    • Lidocaine
    • Phenytoin
    • Tocainide
    • Mexiletine
Lidocaine
  • Xylocaine®
  • Low incidence of toxicity and high effectiveness against arrhythmias during myocardial infarction
  • Given intravenously
Clinical Applications
  • Terminate ventricular tachycardia
  • Prevent ventricular fibrillation after cardioversion
Lidocaine Toxicity
  • Neurologic symptoms: Nystagmus, paresthesia, tremor, nausea, lightheadedness, hearing disturbances, slurred speech, convulsions
Mexiletine
  • Mexitil®
  • Orally active congener of Lidocaine
Clinical Applications
  • Similar to Lidocaine
  • Significant efficacy in relieving chronic pain (especially diabetic neuropathy and nerve injury)
Mexiletine Toxicity
  • Neurologic: Tremor, blurred vision, lethargy

Class IC

  • No effect on action potential
    • Flecainide
    • Encainide
    • Moricizine
    • Propafenone
Flecainide
  • Tambocor®
  • Potent blocker of sodium and potassium channels with slow unblocking kinetics
Clinical Applications
  • Supraventricular Arrhythmias in patients with normal hearts
  • DO NOT USE in ischemic conditions (Post-Myocardial Infarction)
Flecainide Toxicity
  • Proarrhythmic
Propafenone
  • Rhythmol®
  • Primarily used for supraventricular arrhythmias
  • Adverse Drug Reactions (ADRs): Metallic taste, constipation, arrhythmia exacerbation
Moricizine
  • Phenothiazine derivative used for the treatment of ventricular arrhythmias

Class II: Beta-Adrenoceptor Blocking Agents

  • Clinical Applications
    • Atrial arrhythmias
    • Prevention of recurrent infarction and sudden death

Class II Toxicity

  • Asthma

  • AV Blockade

  • Acute Heart Failure

  • Propanolol (Inderal®)

  • Esmolol (Brevibloc®) - a short-acting β-blocker, primarily used as an antiarrhythmic drug for intraoperative and other acute arrhythmias

  • Sotalol - non-selective β-blocking drug that prolongs the action potential

Class III: Drugs that Prolong Effective Refractory Period by Prolonging Action Potential: Potassium Channel Blockers

  • Amiodarone
  • Sotalol
  • Bretylium
  • Dofetilide
  • Ibutilide
Amiodarone
  • Cordarone
  • Given IV or PO
Clinical Applications
  • Serious ventricular arrhythmias
  • Supraventricular arrhythmias
Amiodarone Toxicity
  • Bradycardia
  • Heart block in diseased hearts
  • Peripheral vasodilation
  • Pulmonary & hepatic toxicity
  • Hyper- or hypothyroidism
  • Photodermatitis
    • Gray-blue discoloration in exposed areas of the skin
  • Asymptomatic corneal microdeposits
  • Blocks the peripheral conversion of thyroxine (T4) and triiodothyronine (T3)
  • Potential source of large amounts of inorganic iodine
Dronedaron
  • Structural analog of Amiodarone but lacks iodine atoms
  • First antiarrhythmic drug shown to reduce mortality or hospitalization in patients with atrial fibrillation
Vernakalant
  • Investigational multichannel blocker developed for the treatment of atrial fibrillation
Vernakalant 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: Torsades 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 channels
Effects
  • Slows SA node automaticity and AV nodal conduction velocity
  • Decreases cardiac contractility
  • Reduces blood pressure
Clinical Applications
  • Supraventricular tachycardia
Diltiazem
  • Cardizem®
  • Similar 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®
  • 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 Applications
  • Currently, the drug of choice (DOC) for paroxysmal supraventricular tachycardia
Adenosine Toxicity
  • Flushing
  • Chest tightness
  • Dizziness
Magnesium
  • MOA: Poorly understood; interacts with Na+/K+ ATPase, K+, and Ca2+ channels
Clinical Applications
  • Torsades de Pointes
  • Digitalis-induced arrhythmias
Magnesium Toxicity
  • Muscle weakness with 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 the heart
Clinical Applications
  • Digitalis-induced arrhythmias
  • Arrhythmias associated with hypokalemia
Potassium Toxicity
  • Reentrant arrhythmias
  • Fibrillation
  • Cardiac arrest with overdose

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