PCSK9 inhibitors

[aspiringmd1015]

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what in the world are these?

 

[StIGMA]

Newish LDL reducing monoclonal antibodies (can reduce LDL by 75%; Yes, 75%!). Right now have to be combined with other cholesterol drugs (eg ezetimbe) for insurance coverage. No evidence right now that they reduce MI's, etc (havent been out long enough).

 

[dirty630]

PCSK9 degrades the LDLR, so inhibiting it should increase LDL clearance because of increased hepatocyte LDLRs. Alirocumab and evolocumab are both approved in the US. AFAIK, they're only for familial hypercholesteremia that doesn't respond to statins.

 

[Transposony]

Monoclonal antibodies ( Alirocumab and Evolocumab) against PCSK9 (proprotein convertase subtilisin kexin 9).

LDL-R on hepatocytes bind to LDL and remove them from the circulation.
Normally PCSK9 binds LDL-receptor on the liver that clears cholesterol. This leads to LDL-receptor being destroyed and recycled.
PCSK9 inhibitors binds PCSK9. Therefore, LDL- receptor stays on the liver longer and clears more cholesterol from the body.

Bottomline:

PCSK9 inhibitors leads to decreased LDL-receptor degradation > increased LDL-receptor on the surface of hepatocytes > lowering of LDL cholesterol in blood.

 

[aspiringmd1015]

inhibits a protein that degardes LDLR, increasing LDLR on hepatocytes. cool, thanks guys. it was in a diagram in UW. hoping for this to come on my exam.