lipid lowering drugs

Question 1

mechanism of HMG-CoA reductase inhibitors

Answer 1

1. Inhibits HMG-CoA reductase. (This enzyme is the rate limiting step of cholesterol synthesis.)
2. Upregulate LDL receptors on hepatocyte surface to bind to and internalise as much circulation LDL-cholesterol (LDL-C).

Question 2

use of HMG-CoA reductase inhibitors

Answer 2

lowering cholesterol levels

Question 3

administration of statins

Answer 3

oral, take at night (HMG-CoA is more active at night)

Question 4

adverse effect of statins

Answer 4

Biomedical abnormalities in liver function (raised creatinine kinase levels), Myopathy and Rhabdomyolysis

Question 5

statins contraindicated in

Answer 5

pregnancy and children/teenagers (affects neurodevelopment; cholesterol needed)

Question 6

PCSK9 inhibitors mechanism

Answer 6

Inhibition of PCSK9 that targets LDL receptors for degradation in lysosomes → results in more cell-surface LDL receptors that can bind and internalise LDL

Question 7

adverse effects of PCSK9 inhibitors

Answer 7

Injection site inflammatory reactions

contraindicated in patients who develop hypersensitivity rxns

Question 8

Fibrates/Fibric Acid Derivatives mechanism

Answer 8

Ligands for PPAR-α protein that results in increased lipoprotein lipase (LPL) activity → causes more TG to enter into tissues, causing a decrease in plasma triglyceride levels

Causes VLDL levels to decrease through increasing fatty acid b-oxidation and increase HDL synthesis

Question 9

Omega-3-acid ethyl esters
mechanism

Answer 9

Reduces TG production through functional inhibition of diglyceride acyltransferase (responsible for TG biosynthesis)

Question 10

Omega-3-acid ethyl esters adverse effects

Answer 10

GI symptoms, in some patients could also increase LDL-C, reduces production of thromboxane A2 which can lead to bleeding

Question 11

Bile acid binding resins mechanism

Answer 11

1. Resins bind to negatively charged bile acids in small intestine → lowering bile acid concentration causes hepatocytes to increase conversion of cholesterol to bile acids → decreases intracellular cholesterol concentration
2. Increase hepatic uptake of cholesterol-containing LDL particles (same as statins)

Question 12

Bile acid binding resins used together with

Answer 12

niacin which reduces LDL levels through inhibiting the production of VLDL in the liver and inhibits the breakdown of HDL

Question 13

what are some inhibitors of intestinal sterol absorption

Answer 13

Zetia/Ezetimibe & Sitosterol

Question 14

mechanism of inhibitors of intestinal sterol absorption

Answer 14

inhibits sterol transporter NPC1L1 → reduces cholesterol absorption at small intestine (specific to dietary cholesterol) → reduces LDL