42 Atherosclerosis

Question 1

Where does 25 % of cholesterol production occur?

Answer 1

liver

Question 2

Acetyl Coa becomes HMG CoA and then what happens for it to become cholesterol?

Answer 2

HMG CoA reductase creates mevalonic acid –>[geranyl pyrophosphate–>farnesyl pyrophosphate—> cholesterol]

Question 3

Where is triglycerides taken up? chylomicron?

Answer 3

1. lipoprotein lipase removes in extrahepatic tissues

2. chylomicron taken up by hepatocytes

Question 4

What transfers HDL cholesterol to IDL in the plasma?

Answer 4

LCAT

Question 5

VLDL is synthesized by the liver and lipoprotein lipase hydrolyzes the triglyceride core. How are these remnants converted to LDL?

Answer 5

hepatic lipase removes triglycerides

Question 6

What happens to hepatic LDL?

Answer 6

converted to bile acids

Question 7

What happens to non hepatic LDL?

Answer 7

used for production of hormones cell membranes or stored in esterified form

Question 8

Where else can circulating LDL enter?

Answer 8

macrophages and others to form foam cells which contribute to atheromatous plaques

Question 9

What is HDL formed from? what happens to it

Answer 9

1. phospholipids and apolipoproteins
2. procurement of surface components from trig depleted chylomicrons and VLDL remnants, acquires free cholesterol from tissue sites and other lipoproteins

Question 10

What is the treatment of borderline high cholesterol?

Answer 10

dietary and lipoprotein analysis, with possible drug therapy if CHD or 2 other risk factors

[male, FH, premature CHD, cigarette smoking, hypertension, low HDL, diabetes, obesity]

Question 11

What is the treatment for high cholesterol?

Answer 11

1. dietary if no CHD or less than 2 risk factors

2. dietary +drug if CHD or 2 or more risk factors

Question 12

What is the treatment for very high cholesterol?

Answer 12

Dietary + drug even if no CHD or other risk factors.

Question 13

What do omega-3-ftty acids activate?

Answer 13

PPARalpha- decreases triglycerides- may increase LDL

Question 14

What are the 4 approaches to lowering lipid levels?

Answer 14

1. prevent intestinal absorption of cholesterol or bile acids
2. decrease cholesterol synthesis–>increase LDL receptors–> increase LDL uptake
   3, inhibit VLDL secretion –> decrease LDL production
3. upregulate lipoprotein lipase–> decrease trigs

Question 15

Bile acid sequestrates are what? How do they increase uptake of LDL? Do they increase hepatic production of VLDL?

Answer 15

1. large polymeric cationic exchange resins-insoluble in water
2. increase uptake of LDL from up regulation of LDL receptors
3. Yes

Question 16

What bile sequestrates reduces hyperglycemia?

Answer 16

colesevalam- also has the less side effects and drug drug interactions.

Question 17

What is niacins effect on bile production?

Answer 17

no effect

Question 18

What can long term niacin treatment increase?

Answer 18

insulin resistnce

Question 19

What CYP for lovastatin, simvastatin, atorvastatin? fluvastatin, rosuvastatin?

Answer 19

1. CYP3A4

2. CYP2C9

Question 20

How are HMG CoA reductase inhibitors enhanced absorption?

Answer 20

food

Question 21

All statins undergo glycosylation and interact with?

Answer 21

gemfibrozil

Question 22

What does grape juice inhibit?

Answer 22

CYP3A4 [lovastatin, simvastatin, atorvastatin]

Question 23

PPAR activates polymerase and leads to what 4 things?

Answer 23

1 insulin sensitization

2. anti-proliferative
3. Anti-fibrotic
4. anti-inflammatory

Question 24

Fibric acids lowers VLDL and raises what?

Answer 24

HDL

Question 25

What proteins do fibrin acids up regulate?

Answer 25

lipoprotein lipase, APO A-I, APO` A-II

Question 26

When combining fibrin acids with status, what increased risk is there?

Answer 26

myopathy

Question 27

Is ezetimibe a CYP450 substrate?

Answer 27

No

Question 28

For high LDL cholesterol what classes do we use?

Answer 28

1.bile acid sequestrates 2. nicotinic acid or HMG inhibitor can combine

Question 29

For high LDL and trigs what do we use?

Answer 29

1. weight loss and alcohol restriction 2. niacin or gemfibrozil 3. bile sequestrates or HMG inhibitors [combination of the above increases risk of toxicity]

Question 30

For high trig what do we use?

Answer 30

weight loss | gemfibrozil or nicotinic acid

Question 31

For low HDL what do we use?

Answer 31

1. diet exercise stop smoking | 2. nicotinic acid or gemfibrozil

Question 32

T-F-- the combination of a statin and a bile acid binding resin is more effective than either alone?

Answer 32

True [decreases LDLs more and actually raises HDL]