Hyperlipidemics

Question 1

What breaks down triglycerides into free fatty acids?

Answer 1

Lipoprotein lipase

Question 2

Endogenous route of getting FFA to tissues?

Answer 2

Liver produces VLDL which takes triglycerides to tissues which are broken down by LPL

Question 3

What happens to VLDL after dropping off triglycerides?

Answer 3

Converted to IDL and taken up by liver.

Or IDL can be converted to LDL which is taken up by liver or extrahepatic tissues through LDL receptor

Question 4

LDL and HDL are higher in density because they have less what and more what?

Answer 4

LDL and HDL have less triglycerides and more cholesterol

Question 5

Which lipoproteins are present on chylomicrons? 4

Answer 5

A, B-48, C-2, and E

Question 6

Which lipoproteins are present on VLDL? 3

Answer 6

B-100, C-2, and E

Question 7

Which lipoproteins are present on LDL? 1

Answer 7

B-100

Question 8

Which lipoproteins are present on HDL? 5

Answer 8

A-1, A-2, C-2, D, and E

Question 9

What 2 enzymes re-esterify cholesterol and monoglycerides?

Answer 9

1. ACAT (acetyl-CoA acyltransferase)

2. DGAT (diglyceride acyltransferase)

Question 10

Which transporter transporter cholesterol from the lumen of the SI into the SI?
Which drug inhibits this transporter?

Answer 10

NPC1L1

Ezitemibe (Zetia)

Question 11

What is the lipoprotein that chylomicrons acquire in the SI?
What lipoproteins (2) do they acquire from HDL?
What lipoprotein/cofactor allows chylomicrons to bind to LPL?
Once triglycerides have left, which lipoprotein is released back to HDL?
Which lipoproteins are necessary for reuptake by the liver? 2

Answer 11

Apo-B48
Apo-C2 and Apo E
Apo-C2 does the LPL thing
Apo-C2 is released back to HDL
Apo B48 and Apo E allow remnants to be taken up by liver but it is mostly Apo E

Question 12

VLDL particles receive which lipoprotein in the liver?
Which 2 lipoproteins do VLDL receive from HDL?
What lipoprotein/cofactor allows VLDL to bind to LPL?
Which lipoprotein is an important ligand for LDL receptors?

Answer 12

Apo-B100
Apo-C2 and Apo E
Apo C2 does the LPL thing again
Apo B100 allows LDL to be taken up into the liver or extra-hepatic tissues

Question 13

HDL is transported to the liver where it binds to (what) though which lipoprotein? What is transferred to hepatocytes?

Answer 13

HDL binds to SR-B1 through Apo A-1

Cholesterol esters are selectively delivered to hepatocytes

Question 14

Cause of primary chylomicronemia?

Answer 14

Deficient LPL activity

Question 15

Cause of familial hypertriglycerideemia?

Answer 15

Deficient removal of VLDL or chylomicrons

Question 16

Cause of familial combined hyperlipidemia/hypercholesterolemia?

Answer 16

Increased VLDL production

Question 17

Cause of familial dysbetalipoproteinemia?

Answer 17

Deficient clearance of VLDL, IDL, and chylomicron remnants due to dysfunction or absence of Apo E

Question 18

Cause of familial hyper-cholesterolemia

Answer 18

LDL-R impairment

Question 19

Cause of familiar ligand-defective apoB?

Answer 19

Mutation in apo-B100 resulting in impaired endocytosis of LDL

Question 20

Fibric acid derivatives (2(

Answer 20

Gemfibrozil and fenofibrate

Question 21

How do the fibric acid meds work? 3

Answer 21

1. Increase plasma HDL
2. Increases reverse cholesterol transport
3. Increased fatty acid oxidation

Question 22

Gemfibrozil and fenofibrate upregulate which transcription factor?

Answer 22

Activate/upregulate the PPAr receptor

Question 23

Which lipoproteins are upregulated with gemfibrozil and fenofibrate?

Answer 23

Apo A1 and Apo A2

Question 24

Why should gemfibrozil and fenofibrate not be combined with statins?

Answer 24

Increased risk of myopathy

Question 25

How do cholestyramine. colesevelam, colestipol work?

Answer 25

Bind bile acids and bile salts in the intestines and shat them out. Liver has to increase synthesis of bile acid to replaces what was lost

Question 26

How do the bile binders remove LDL?

Answer 26

Liver requires LDL to replace lost bile acids so there is an upregulation of LDL-R in the liver

Question 27

Bile binders would help treat which disorder?

Answer 27

Familiar hypercholesterolemia (LDL-R issues)

Question 28

Which population should not be taking bile-binders?

Answer 28

Anyone with high triglycerides

Question 29

Bile binders are drug of choice for which 2 populations?

Answer 29

1. Children

2. Pregnant or lactating women

Question 30

Niacin is used to lower (2) and raise (1)?

Answer 30

Lower VLDL and LDL, raise HDL

Question 31

How does niacin work exactly?

Answer 31

Niacin decreases lipase activity in adipose tissue. This decreases FFA in the blood which means the liver cannot produce triglycerides as much.
This causes less VLDL and LDL delivery to peripheral cells. The liver needs cholesterol so there is an upregulation of cholesterol removal by HDL.
This cholesterol is brought to liver to be used for bile acids and other stuff

Question 32

How effective is niacin?

Answer 32

Not very effective which is why it is used in combination therapy

Question 33

4 common side effects of niacin?

Answer 33

1. Flushing/itching (niacin flush)
2. Hyperuricemia
3. Hyperglycemia
4. Hepatotoxicity

Question 34

Safest niacin + statin combination?

Least safest combination?

Answer 34

Niacin plus fluvastatin is good.

Niacin plus lovastatin is bad

Question 35

Ezetimibe blocks intestinal absorption of cholesterol and bile acids through which transporter?

Answer 35

Niemann-Pick C1 like 1 protein

Question 36

Statin adverse effects (2)

Answer 36

1. Liver toxicity in low percentage of patients

2. Never use in pregnancy