Hyperlipidemia Q2L

Question 1

What % of annual deaths does CHD account for?

Answer 1

50%

Question 2

What is incidence of CHD correlated with?

Answer 2

positively associated with high total cholesterol and elevated LDL in the blood

Clinical artherosclerotic disease confers high risk for CHD: Clinical CHD, Symptomatic carotid artery disease, symptomatic carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm

Question 3

What are the risk factors for CHD?

Answer 3

smoking, HTN, low HDL, family Hx of premature CHD, age (>45yrs men, >55 women)
HDL >60mg/dl is a negative risk factor (good cholesterol)

Question 4

How much reduction in mortality due to CHD can clinical management provide?

Answer 4

30-40% (clinical management = lifestyle changes + drug therapy)

Question 5

What are the different types of familial hyperlipidemias?

Answer 5

Type I, IIA, IIB, III, IV, V

Question 6

What is Type I hyperlipidemia?

Answer 6

(Familial hyperchylomicronemia)
◦ Massive fasting hyperchylomicronemia
◦ Deficiency of lipoprotein lipase
◦ NOT associated with an increase in coronary heart disease

Question 7

What is Type IIA hyperlipidemia?

Answer 7

(Familial hypercholesterolemia)
◦ Elevated LDL with normal VLDL caused by a block in LDL degradation
◦ Characterized by an increased serum cholesterol level but normal TG levels
◦ Correlated to ischemic heart disease
◦ Treated with cholestyramine, niacin, or a statin

Question 8

What is Type IV hyperlipidemia?

Answer 8

(familial hypertriglyceridemia)
◦ Increased VLDL levels with normal or decreased LDL levels resulting in normal to increased cholesterol and GREATLY elevated TG
◦ Overproduction and / or decreased removal of VLDL and TG in serum
◦ Common
◦ Treated with niacin and / or fenofibrate

Question 9

What are the important apolipoproteins and their functions?

Answer 9

Apoliproprotein B-48 + PL, TG, CE = Chylomicrons.
B-100 binds to LDL receptor
C-II cofactor for activating lipoprotein lipase
E mediates remnant uptake

Question 10

What are the important apolipoprotein functions?

Answer 10

Apolipoproteins bind lipids to form lipoproteins.

Question 11

What is the primary goal of hyperlipidemia treatment?

Answer 11

reduction of the LDL level

Question 12

What are the desirable levels of cholesterols?

Answer 12

LDL: < 200

TG <150

Question 13

What is xanthalasma?

Answer 13

fat deposits in the skin (can be anywhere, but we will likely see them in the eyelids)

Question 14

What is arcus?

Answer 14

cholesterol deposits in the corneal stroma. Common in the elderly, but can occur earlier in life due to hypercholesterolemia.

Question 15

What are treatment options for hypertriacylglycerolemia?

Answer 15

1. diet and exercise are the primary modes

2. niacin and fibric acid derivatives (fibrates)

Question 16

How do ‘-statins’ class of drugs work?

Answer 16

Note: HMG is the precursor of cholesterol

1. inhibits the first step of cholesterol synthesis –> decreases amount of cholesterol in the cell
   - decreased cholesterol in cell stimulates synthesis of LDL receptors-> increase amount of LDL receptors promotes uptake of LDL in blood
   - decreased cholesterol also decreases VLDL secretion from cell
2. improves coronary endothelial function
3. inhibits platelet thrombus formation
4. anti-inflammatory

Question 17

Statin SEs

Answer 17

SE: liver failure, myopathy, CI in pregnancy

Question 18

What is niacin used for?

Answer 18

Most effective agent for increasing HDL*

Question 19

Niacin Side effects

Answer 19

SE: intense cutaneous flush and pruritus, inhibits tubular secretion of uric acid

Question 20

What are the fibrates?

Answer 20

Fibrates increase lipoprotein lipase therefore lowering serum triacylgycerols and increasing HDL levels-> use to treat hypertriacylglycerolemias

Question 21

Fibrate SEs

Answer 21

SE: gallstones (more cholesterol into gall bladder), myositis

Question 22

Fibrate MoA

Answer 22

Fenofibrate and Gemfibrol binds to PPAR-alpha

Question 23

What are the bile acid sequestrants?

Answer 23

Colesevelam, colestipol, cholestyramine

-prevent reabsorption of bile acids and salt, therefore liver uses more cholesterol to replace the bile

Question 24

Bile Acid sequesterant SEs

Answer 24

SE: constipation, nausea, flatulence, impair the absorption of fat soluble vitamins (DAKE)

Question 25

An example of cholesterol absorption inhibitor?

Answer 25

Ezetimibe

Question 26

Which drug to start if a patient has high cholesterol?

Answer 26

Statins

Question 27

Which drug to start if a patient has high TG?

Answer 27

Fibrates

Question 28

Which drug to start if a patient has low HDL?

Answer 28

Niacin

Question 29

What is the advantage of combo cholesterol drugs?

Answer 29

Synergistic effect and better compliance.

Question 30

What is the disadvantage of combo cholesterol drugs?

Answer 30

Liver and muscle toxicity occurs more frequently, cost