Hyperlipidemia

Question 1

What does intracellular effects does cholesterol have in the liver?

Answer 1

1. Decrease activity of HMG CoA Reducatase
2. Activates ACAT –> stores cholesterol as cholesterol ester.
3. Inhibits LDL-R gene transcription

Question 2

What is the FIRST step in treatment of all forms of primary hyperlipidemia?

Answer 2

Diet modification. Often the only treatment necessary.

Question 3

When do you use drug therapy for hyperlipidemia?

Answer 3

When diet and weight reduction hasn’t lowered total and LDL cholesterol sufficiently after 6-12 months.

Question 4

What are the most effective drugs for hyperlipidemia? What are they contraindicated in?

Answer 4

The statins (HMG-CoA reductase inhibitors). They reduce LDL and TGs and increase HDL.

They are contraindicated for pregnant or nursing women.

Question 5

What is the mechanism of statins?

Answer 5

They are reversible, competitive inhibitors of HMG-CoA reductase and inhibit cholesterogenesis in the liver.

The reduced free cholesterol levels in the liver causes an increase (via SREBP) in the synthesis of LDL receptors and a decrease in their degradation and also reduce VLDL production.

Question 6

What two statins have longer half-lives and can be administered once a day?

Answer 6

Atorvastatin and Rosuvastatin

Question 7

What is the best agent for increasing HDL-C?

Answer 7

Nicotinic acid (niacin). It also lowers LDL-C levels.

Question 8

What agent is especially useful for patients with both hypertriglyceridemia and low HDL-C levels?

Answer 8

Niacin

Question 9

What are the therapeutic effects of niacin?

Answer 9

1. Reduces triglyceride synthesis in liver (less VLDL production)
2. Decreased lipolysis in adipose tissue (less free fatty acids to liver, thus less TG synthesis)
3. Reduces clearance of HDL apoAI (raises HDL-C levels)

Question 10

What are niacin’s major side effects?

Answer 10

Hepatotoxicity, hyperglycemia and hyperuricemia. Also, flushing/pruritis offace and uper trunk and other skin problems, as well as peptic ulcer disease.

Question 11

What is niacin contraindicated in?

Answer 11

Diabetes mellitus or history of gout.

Question 12

What are the best drugs for patients with severe hypertriglyceridemias?

Answer 12

Fibric Acid Derivatives (Fibrates)

Question 13

How are fibrates believed to lower lipoprotein levels and raise HDL levels?

Answer 13

Through stimulation of PPAR-alpha.

Question 14

Which fibrates have the most and least risk for gallstone formation?

Answer 14

Most: clofibrate
Least: gemfibrozil

Question 15

What is the mechanism behind bile acid sequestrants?

Answer 15

They prevent the reabsorption of bile in the intestine, causing the liver to increase bile acid synthesis. This causes the hepatic cholesterol content to decline, stimulating the production of LDL receptors.

Question 16

What do bile acid sequestrants slightly increase the level of?

Answer 16

Triglyceride and HDL levels. (Contraindicated in hypertriglyceridemia)

Question 17

What bad things can bile acid sequestrants do?

Answer 17

Impairs absorption of fat soluble vitamins and various drugs.

Question 18

What does ezetimibe do?

Answer 18

Inhibits cholesterol absorption by enterocytes in the small intestine.

Question 19

What is ezetimibe often combined with?

Answer 19

Statins. Statins inhibit cholesterol biosynthesis and increase intestinal absorption, while ezetimibe inhibits intestinal absorption and increases cholesterol biosynthesis.

Question 20

What is the current combination therapy?

Answer 20

Resin and statin. Resins inhibit bile acid reabsorption and statin inhibits cholesterol biosynthesis, all of which increases LDL receptor production.

Question 21

What should never be combined?

Answer 21

Statins and fibrates. (Increased risk of myositis)

Question 22

What do the three bile acid sequestrants have in commmon?

Answer 22

They all start with “chole-“ or something like that.