Na Channels blockers Flashcards
What does ischemia lead to on a cellular level?
Decreased O2 in tissue
- Cellular Hypoxia
- Mitochondria damage
- Diminished Intracellular ATP
Why is ATP so important for cardiac function?
Provided energy needed for the Na+/K+/ATPase transport pump
What is the purpose of the Na/K/ATPase pump?
Pumps more 3:2 Na:K ions out than K ions in.
- Net loss of + charge
- leads to increasing negativity
- Repolarization happens
What happens when this Na/K/ATPase pump goes out?
cells stays more positive and doesnt repolarize
What do the cells do the compensate for the loss of ATP?
Activates K+ATP channels which open at reduced values of ATp
- Allows outflow of K+ so cells can depolarize
What is the net effect of the K+ATP channels?
Too much extracellular K+ and Too much Na+ intracellulary (backwards)
- More positive (less negative) and thus depolarized
- Leads to delayed depolarization and quicker repole
- High intracellular Ca 2+
What does decrease in ATP do the Action Potential curve?
Depolarization slope is less steep and the repole (refractory period) shortens
-shape determined by specific perm to diff ions
What does decrease in ATP do to the sodium channels?
Channel is dependent on membrane potential
- More positive membrane means channels become inactivated
- Slower channel recovery
How does the affect sodium channels due to decreased ATP lead to Action potential curve changes?
Less sodium channels open to cause the depolarization (curve is less steep)
- Decrease CONDUCTION velocity
** Altered impulse conduction
What does slowed conduction lead to?
Unidirectional block
If functional: Impulse reaches tissue that is still in refractory state from previous stimulation
Fixed: scarring or fibrosis replaces myocyte
What is accommodation?
Fast response action potential begins to looks like slow response AP
-Leads to altered impulse formation
What can the altered impulse formation lead to?
Display spontaneous depolarization and automaticity
- Thus can lead to ectopic beats or arrhythmia
What can ischemia thus lead to?
Depolarized membrane potential that can potentially create arrhythmias
What are the MOA of antiarrhythmics?
Reduced pacemaker activity
- modify conduction/refractoriness
How doe we deal with reentry?
- Slow conduction further
- Speed conduction
- Alter effective refractory period
What are the Class 1 drugs MOA?
Na Channel blockage
- Alters AP duration and kinetics of Na Channel blockage
What are the Class II drugs and their MOA?
Beta-Andrenoceptor Blockade
-Blocks the SNS effects on the heart
What are the Class II drugs and their MOA?
K channel blockage
- Prolongation of the effective refractory period
What are the Class IV drugs?
Ca channel blockade
- slows conduction where depole is Ca dependent
What do Na channel blockers do the AP curve?
Elongates phase 0
- Slows conduction
- binds to channels in the the inactivated state
What doe K channel blockers do the AP curve?
Slows the efflux of K during phase 3 prolonging the refractory time of the cell
- Repole takes longer
How do we deal with accommodation?
Change cell from altered Ca dependent back to Na dependent depole by altering Ca2+ perm.
What do Ca channel blockers do the AP curve?
Slows influx of Ca by blocking L-type channels
- allows Na to take back over for repole
What are Class 1 useful for? Which tissues do they affect?
treating tachycardias
- increases type needed for phase 0 (decreases slope and amplitude)
- only affect non-nodal tissues
