Lipid Lowering Drugs

Question 1

Give an example of HMG-CoA reductase inhibitors. Explain its mechanism of action.

Answer 1

Atorvastatin, pravastatin, simvastatin

1. Inhibition of HMG-CoA reductase, which inhibits the rate limiting step for cholesterol synthesis, reducing cholesterol levels
2. Upregulates LDL receptors on cell surface, reducing plasma LDL level

Question 2

List the adverse effects of HMG-CoA reductase inhibitors.

Answer 2

Contraindicated in pregnancy, nursing mothers and children as cholesterol is needed for neurodevelopment
Biomedical abnormalities in liver function
Myopathy and rhabdomyolysis

Question 3

Give an example of a PCSK9 inhibitor. Explain its mechanism of action.

Answer 3

Evolocumab, alirocumab

1) Inhibition of hepatic PCSK9, hence reducing LDL receptors degradation in lysosomes through endocytosis
2) Reduced LDL receptor degradation, hence more LDL receptor available to bind and internalise LDLs

Question 4

List the adverse effects of PCSK9 inhibitors.

Answer 4

Contraindicated in patients with hypersensitivity reaction
Inflammation at injection site
Increased incidence of nasopharyngitis and sinusitis

Question 5

Give an example of fibrates. Explain its mechanism of action.

Answer 5

Gemfibrozil, fenofibrate

1) Ligands of PPAR-a protein, which increases activity of lipoprotein lipase, causing a decrease in plasma triacylglycerol level
2) Levels of VLDL decrease and HDL increase

Question 6

List the adverse effects of fibrates.

Answer 6

Nausea
Skin rashes
Gall stones
My Osiris

Question 7

Give an example of Omega-3-Acid ethyl esters. Explain its mechanism of action.

Answer 7

Omacor

1) Reduces hepatic triglyceride production and increases triglyceride clearance from VLDL
2) Functional inhibition of diglyceride acyltransferase, reducing triglyceride biosynthesis
3) Increase fatty acid breakdown via beta-oxidation
4) Increase lipoprotein lipase activity

Question 8

List the adverse effects of Omega3-Acid ethyl esters.

Answer 8

Contraindicated in patients allergic to fish
GIT effects like nausea and vomiting
Increased LDL-C
Reduces thromboxane A2 production, leading to increased bleeding time

Question 9

Give an example of bile acid binding resins. Explain its mechanism of action.

Answer 9

Cholestyramine

Anion exchange resins bind negatively charged bile acids in small intestine. Lowered bile acid concentration increases conversion of cholesterol to bile acids, decreasing intracellular cholesterol concentration. This activates an increased hepatic uptake of cholesterol-containing LDL particles, leading to a fall in plasma LDL.

Question 10

List the adverse effects of bile acid binding resins.

Answer 10

GIT effects like nausea and vomiting
Impaired absorption of vitamins A, D, E and K

Question 11

Give an example of intestinal sterol absorption inhibitor. Explain its mechanism of action.

Answer 11

Ezetimibe

Inhibits sterol transport NPC1L1 to reduce cholesterol absorption at small intestine.

Question 12

List the adverse effects of sterol inhibitor.

Answer 12

GIT effects like nausea and vomiting
Rhabdomyolysis, especially when taken with statins
Low incidence of reversible hepatotoxicity