Friday, October 9, 2020

Mechanism of action of lipid-lowering drugs

Hey everyone! 

I wanted to talk about the new lipid-lowering drug, bempedoic acid. But first, let’s just quickly go through the mechanism of action of the existing lipid-lowering drugs:

Statin reduces cholesterol synthesis by HMG-CoA Reductase inhibition.

Ezetimibe inhibits cholesterol absorption from the intestine.

Fibrates activate PPAR-alpha to induce HDL synthesis and increase triglyceride degradation by activating lipoprotein lipase.

PCSK9 inhibitors (Evolocumab and Alirocumab) inactivate LDL receptor degradation.

Niacin inhibits lipolysis in adipose tissue.

Cholestyramine and colestipol are bile acid sequestrants which prevent bile from being absorbed so
the liver uses cholesterol to make more bile.

The new drug, bempedoic acid, works upstream from the HMG-CoA Reductase enzyme in cholesterol synthesis it inhibits ATP Citrate lyase (ATC) enzyme affecting both cholesterol and carbohydrate pathway. It is indicated for people who are maxed out on statin or have an intolerance to statin. However, it is not the mainstay treatment. It is interesting to know that extension of the cholesterol pathway can also help us reduce our lipids.

Written by Tasneem Adenwala

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