Flashcards in Na Channels blockers Deck (38):
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?
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
-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?
-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?
- increases type needed for phase 0 (decreases slope and amplitude)
- only affect non-nodal tissues
What is the reason for subclasses of Class 1 Na blockers?
Affects action potential duration (APD) and effective refractory period (ERP)
- Diff affects on slope of phase 0
What is the effects of ERP from Na channel blockers from?
specific secondary activity of these drugs on efflux of K+ in phase 3
Which subdivision of class one is best at Na channel blockage?
Which class 1 subdivision is best at increase the ERP?
Class 1A kinetics with Na channel and effect?
- slow rate of rise of AP (phase 0)
- Prolongs AP (increase refractory)
Class 1B kinetics with Na Channel and effect?
- Shorten refractory period (phase 3)
-Decreases duration of AP
Class 1C kinetics with Na channel and effect?
- Markedly slows phase 0 Depole
-No effect on refractory
What are class II Beta Andrenoceptor blockers mainly used for?
Prevent and treat supraventicular arrhythmias and reduce ectopic depole and sudden death in pts with MI
What are Beta blocker effects?
-Decrease AV node conduction
-Increase the AV node refractory period
-Little to no effect on ventricular conduction and repolarization
What suffix do beta blockers end in?
What is propranolol AE's?
Adverse effects include bronchospasm, bradycardia, fatigue
What is Acebutolol mainly used for?
better for use in patients with asthma (to avoid the adverse effects such as bronchospasm
What is Esmolol used for?
short acting blocker used primarily for intraoperative and acute arrhythmias