Pharmacology - CHF

Question 1

What are Ryanodine receptors?

Answer 1

A calcium activated channel (at low concs) that releases more calcium

RyR1 –> Skeletal

RyR2 –> Cardiac

RyR3 –> Brain and other tissues

So when activated it stimulates contraction

Question 2

What is SERCA?

Answer 2

A channel that is activated by high levels of calcium and cathecholamines, causing phophorylation of phospholamban (PLN) by PKA

This causes Ca2+ to be re-uptaken into the SR

Question 3

What is NCX?

Answer 3

A channel that can be used to pump either Ca2+ or Na+ into the cell

Normal mode (repolarisation) –> Activated by high calcium

Removes 1 Ca2+ for 3 Na+ –> causing relaxation

Reverse mode (depolarisation) –> Activated by high cystolic sodium

Expels 3 Na+ for 1 Ca2+

Question 4

What’s the difference between Inotropic and Lusitropic?

Answer 4

Inotropic –> Contraction

Lusiotropic –> Relaxation

Question 5

How do positive inotropes, like Milrinone and Enoximone work?

Answer 5

They are PDEs….

So prevent the breakdown on cAMP –> causing an increase in PKA/Ca2+, and so more contraction

Question 6

How does Levosimendan work?

Answer 6

Binds to TroponinC in a Ca2+ dependent way –> prolonging its action (systole/contraction)

Question 7

How does Digoxin (a cardiac glycoside) work?

Answer 7

Binds competitivly to K+ binding sites on the Na+/K+/ATPase, blocking Na+ from moving out of the cell

This promotes the NCX transporter to go into reverse, bringing Ca2+ into the cell…..causing heart contractions