Antiarrhymatic agents

Question 1

Slow Action Potentials vs Fast Action Potentials:

Answer 1

• Slow APs (Gradual hill on ECG)
  
  • Occur in cells of the SA & AV node
  • Calcium Dependent
  • class 2 & 4 drugs
  • 3 features
    
    • Phase 0
      
      • slow depolarization caused by Ca2+ influx
        
        • slower than Fast APs
    • Phase 1, 2, 3
      
      • Phase 1 &2=absent
      • Phase 3=not significant=K+ eflux
    • Phase 4:
      
      • Depolarization=GENTLE HILL
      • Na+ influx
• Fast APs-Steep incline
  
  • Occurs in fibers of His-Purkinje system and atrial and ventricular muscle
  • Sodium Dependent
  • Class 1 & 3 drugs
  • 5 distinct phases
    
    • Phase 0
      
      • depolarization; Na+ influx
    • Phase 1:
      
      • (partial) repolarization; K+ eflux
    • Phase 2:
      
      • plateau (potassium mediated); Ca2+ influx, K+ eflux
    • Phase 3:
      
      • repolarization; K+ eflux
    • Phase 4:
      
      • stable potential (that can be depolarized again); K+ eflux

Question 2

Pacemaker vs cardiomyocyte

Answer 2

• Pacemaker
  
  • Slow cells
  • SA node
• Cardiomyocyte
  
  • fast cells

Question 3

Arrhythmia

Answer 3

• Deviation from a normal cardiac rhythm
• unexplained by physiology
• Normal: 60-100 BPM
• Bradycardia: <60 BPM
• Tachycardia: >100 BPM
  
  • majority of abnormal

Question 4

Mechanisms responsible for Arrhythmia:

• Abnormal Impulse formation:
  
  • ​Enhanced Automaticity-faster than SA node
    
    • abnormal impulses form faster than the impusled formed by the SA node
    • result in fast arrythmia=tachycardia
  • Triggered activity- after depolarization (early or late)
    
    • _​_significant enough to trigger AP
• Abnormal Impulse Conduction
  
  • ​Reentry rhythms:
    
    • abnormal conduction in which impuses repetitively move through tissue previously excited by the same impulse
    • self sustaining but not self-initiated
    • require an area of unidirecitonal block–>associated with an area of damage
      
      • previous ischemia or myocardial infarction
• BOTH

Question 5

Normal Impulse Conduction vs Abnormal Impulse Conduction:

Answer 5

• Normal:
  
  • Impulse comes down purkinje fibers & into ventricles
  • impulse spreads
  • some cancel each other out, bc they both hit tissue that can’t be depolarized
  • others spread to tissues to depolarize
• Unidirectional Block (ischemia or myocardial infarction)
  
  • Impulse comes down purkinje fibers
  • Unidirectional block–Impulse can only go one way
    
    • impulses don’t cancel each other out (normal)
    • impulse cycles around to other side of block and IS ALLOWED to cross the damaged tissue=retrograde impulse
  • AP keeps cycling–> results in self-sustaining reentry arrythmia

Question 6

Long QT interval

Answer 6

start arrythmias within the heart

Question 7

Principles of Antiarrhythmic Drug use:

Answer 7

• identiy the arrythmia mechanism (understand cardia electrophysiology) and remove and precipitating factors
  
  • Precipitating factors=drugs that prolong QT interval
• Establish Goals of Treatment
  
  • Decision to Treat
  • risk vs benefit
  • examine all modalities available
• Minimize risk
  
  • proarrythmic effects
  • monitor BLood levels

Question 8

Anti-Arrhythmic Drugs: Therapy and Therapeutic Goal

Answer 8

• Anti-arrhythic drug therapy=DANGEROUS
  
  • can exacerbate existing arrhythmias and create new ones
  • benefits must outweigh risks greatly
  • There are no safe drugs, many patients have died during clinical trials
• Goal:
  
  • blunt or prevent abnormal impulse formation and/or abnormal conduciton

Question 9

Vaughn-Williams Classification of antiarrhythmic agents:

Answer 9

• Classified based on MOA only
• 4 classes and other (5 total)
• Class 1:
  
  • block Sodium Channels w/fast APs
• Class 2: