Lipid Lowering Drugs

Question 1

How do statins work?

Answer 1

Statins are HMG-CoA reductase inhibitors.
HMG-CoA reductase would usually convert HMG-CoA to mevalonate. Prevention decreases cholesterol synthesis.

1. Decreased concentration of cholesterol in cell due to statins.
2. Low cholesterol stimulates LDL receptor synthesis.
3. Increased LDL receptors = LDL uptake from blood (good)
4. Low cholesterol decreases secretion of VLDL (precursor to LDL)

Results in decreased production of cholesterol in increased clearance of LDL.

Question 2

How much % CVD risk is reduced from a 1mmol reduction in LDL-C?

Answer 2

22% reduction in CVD

Question 3

How does Ezetimibe work?

Answer 3

Blocks uptake of dietary cholesterol and blocks reabsorption of bile.
Makes you use your own bile from gut, which uses cholesterol to make.

Has some GI side effects, as it works on the gut.

Question 4

What do PCSK9 proteins do and how can they be used to lower LDL?

Answer 4

PCSK9 binds to LDL receptors, preventing LDL uptake from blood into cells.
PCSK9 inhibitors prevent this, allowing LDL receptors to uptake LDL from blood.

Also trialled monoclonal antibodies against PCSK9.

Question 5

In what occasion is alirocumab and evolocumab used?

Answer 5

Adjunct to proper diet and exercise in people with familial hypercholesterolaemia.

Question 6

How does Inclisiran work?

Answer 6

Inclisiran interferes with PCSK9.

Significant side effects:

• Nasopharyngitis
• Injection site reactions

Question 7

How do fibrates work?

Answer 7

Increases FFA beta-oxidation, decreasing FFA synthesis and thus VLDL formation.