Intro to Antiarrhythmics Drugs - Nordgren

Question 1

What is an Arrhythmia?

Answer 1

• Any condition of the heart in which the electrical activity is:
  
  • Faster (tachycardia)
  • Slower (bradycardia)
  • Irregular

Question 2

Normal cardiac rhythm depends on what three things?

Answer 2

1. Impulse site of origin
2. Rate of impulse
3. Conduction (Transport) of Impulse

Question 3

What is the Potassium Equilibrium Potential?

Electrochemical movement?

Answer 3

-90mV

• Charge (electro):
  
  • K⁺ wants to move into cell
• Concentration (chemical):
  
  • K⁺ want to leave cell

Question 4

What is the Sodium Equilibrium Potential?

Electrochemical movement?

Answer 4

+70mV

• Charge (electro):
  
  • Na⁺ wants to leave cell
• Concentration (chemical):
  
  • Na⁺ want to move into cell

Question 5

What effect will inhibiting the sodium channels have on the action potential of the cardiac cell?

Answer 5

• Fast response/Contractile Myocytes:
  
  • elongates depolarization (phase 0)
  • slows conduction

Question 6

What effect will inhibiting the potassium channels have on the action potential of the cardiac cell?

Answer 6

• Prolong repolarization (phase 3)
  
  • Slows repolarization
  • Increases AP duration
  • Increases refractory period

Question 7

What effect will inhibiting the calcium channels have on the action potential of the cardiac cell?

Answer 7

• Fast Response/Cardiac Myocytes:
  
  • Shortens plateau of AP (phase 2)
  • Reduces force of contraction
    
    • Less Ca²⁺ available to bind troponin
• Slow Resonse/Pacemaker cells:
  
  • Slows rise of AP (phase 0)
    
    • consequently prolongs repolarization at AV node → Decreased conduction velocity
  • Takes longer to reach threshold → Decreased HR

Question 8

Atrial, Purkinje, and Ventricular Cells are dependent on what ion current for depolarization?

Answer 8

Na⁺

Question 9

SA and AV nodal cells are dependent on what ion current for depolarization?

Answer 9

Ca²⁺

Question 10

What are the three states of voltage gates in an active cell membrane?

Answer 10

• Resting
  
  • activation gate closed
  • inactivation gate open
• Activated
  
  • both activation and inactivation gates open
• Inactive
  
  • activation gate open
  • inactivation gate closed

Question 11

What is the key factor in pathophysiology of arrhythmias and the drugs used to treat them?

Answer 11

Relation between RESTING potential of a cell and the number of ACTION POTENTIALS that can be evoked.

• membrane potential determines how many channels are open
  
  • e.g. Na⁺ channel inactivation gates close between -75 and -55 mV
    
    • if AP is evoked at -60mV, fewer Na⁺ channels will be available for diffusion of Na⁺ than if the AP occurred at -80mV

Question 12

What factors lead to arrhythmia?

Answer 12

• Many factors… but they all lead to arrhythmia through disturbances of either:
  
  • 1)Impulse Formation
  • 2) Impulse Conduction!

Question 13

What effect do Na+-channel blockers have on the pace-maker rate, refractory period, and velocity of conduction?

Answer 13

• Alters AP duration & kinetics of Na+ channel blockade
  
  • Steady-state reduction in # of available unblocked channels, which reduces excitatory currents to a level below that required for propagation

Question 14

What effect do Ca²⁺-channel blockers have on the pace-maker rate, refractory period, and velocity of conduction?

Answer 14

• Slows conduction where depolarization is Ca2+ dependent
• Steady-state reduction in # of available unblocked channels, which reduces excitatory currents to a level below that required for propagation

Question 15

What effect do K⁺-channel blockers have on the pace-maker rate, refractory period, and velocity of conduction?

Answer 15

• Prolongation of the effective refractory period
• Prolongation of recovery time of the channels still able to reach the rested and available state, which increases refractory period