Pharmacology of Anti-Hyperlipidemics

Question 1

Generally statins are well-tolerated. This, however, is a rare and life-threatening ADR that may lead to renal failure.

Answer 1

Rhabdomyolysis (breakdown of skeletal muscle releasing myoglobin into the blood)

Question 2

True/False. Statins are contraindicated in pregnancy.

Answer 2

True. They are contraindicated and pregnant and breast feeding women

Question 3

What ADRs are associated with fibrates?

Answer 3

Cholecystitis & gallstones

Question 4

What is the MOA of Ezetimibe?

Answer 4

Blocks NPC1L1 receptors to prevent cholesterol absorption in the intestines

Question 5

These drugs prevent reabsorption of bile acids by trapping them in the intestines for excretion.

Answer 5

Bile Acid Resins - Cholestyramine, Cholesevelam, Colestipol

Question 6

What is the MOA of statins?

Answer 6

Inhibit the HMG-CoA Reductase (rate-limiting step of cholesterol synthesis). This leads to increased expression of LDL receptors on hepatocytes

Question 7

What is the primary target of antihyperlipidemic drugs?

Answer 7

To decrease LDL, often done by impacting cholesterol synthesis and absorption

Question 8

What is the ligand that facilitates LDL entry into hepatocytes?

Answer 8

ApoB100

Question 9

These drugs primarily work to decrease triglycerides by increasing lipoprotein lipase to breakdown fatty acids.

Answer 9

Gemfibrozil, Fenofibrate

Question 10

What is the most common ADR associated with statins?

Answer 10

Myalgia (due to inhibition of the Coenzyme Q10 in skeletal muscle cells).

Hepatotoxicity is another significant ADR

Question 11

What is the function of HDL?

Answer 11

To scavenge free cholesterol in the blood for delivery to hepatocytes

Question 12

This statin should be given with food.

Answer 12

Primvastatin

Question 13

This drug is primarily intended to increase HDL, but also decreases LDL and triglycerides. What is its MOA?

Answer 13

Niacin - inhibits hormone sensitive lipase thus decreasing fatty acid supply in the liver

Question 14

What is the MOA of Alirocumab?

Answer 14

Inhibitor of the PCSK9 enzyme, which breaks down LDL receptors on hepatocytes. This leads to increased expression of LDL receptors

Question 15

What is the MOA of Gemifibrozil?

Answer 15

Increases activity of lipoprotein lipase to increase fatty acid breakdown

Question 16

Niacin is not a first-line therapy due to its various side effects. What are the common ADRs?

Answer 16

Flushing, hyperuricemia, hyperglycemia

Question 17

Bempedoic acid inhibits the ATP citrate lystae, a step in cholesterol synthesis before the HMG-CoA Reductase. Why does this drug not cause myalgia?

Answer 17

Only active in hepatocytes. Does not inhibit cholesterol synthesis in skeletal muscle cells

Question 18

True/False. Alcohol increases HDL synthesis.

Answer 18

False - alcohol increases VLDL and triglyceride synthesis

Question 19

What ADRs are associated with cholestyramine?

Answer 19

Elevated triglycerides, gallstones, constipation

Question 20

These statins are prodrugs administered at night.

Answer 20

Lovastatin & Simvastatin

Question 21

What is the first line therapy for hypercholesterolemia?

Answer 21

Statins

Question 22

What are the most commonly used statins?

Answer 22

Atorvastatin & Rosuvastatin