42 Atherosclerosis Flashcards
Where does 25 % of cholesterol production occur?
liver
Acetyl Coa becomes HMG CoA and then what happens for it to become cholesterol?
HMG CoA reductase creates mevalonic acid –>[geranyl pyrophosphate–>farnesyl pyrophosphate—> cholesterol]
Where is triglycerides taken up? chylomicron?
- lipoprotein lipase removes in extrahepatic tissues
2. chylomicron taken up by hepatocytes
What transfers HDL cholesterol to IDL in the plasma?
LCAT
VLDL is synthesized by the liver and lipoprotein lipase hydrolyzes the triglyceride core. How are these remnants converted to LDL?
hepatic lipase removes triglycerides
What happens to hepatic LDL?
converted to bile acids
What happens to non hepatic LDL?
used for production of hormones cell membranes or stored in esterified form
Where else can circulating LDL enter?
macrophages and others to form foam cells which contribute to atheromatous plaques
What is HDL formed from? what happens to it
- phospholipids and apolipoproteins
- procurement of surface components from trig depleted chylomicrons and VLDL remnants, acquires free cholesterol from tissue sites and other lipoproteins
What is the treatment of borderline high cholesterol?
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]
What is the treatment for high cholesterol?
- dietary if no CHD or less than 2 risk factors
2. dietary +drug if CHD or 2 or more risk factors
What is the treatment for very high cholesterol?
Dietary + drug even if no CHD or other risk factors.
What do omega-3-ftty acids activate?
PPARalpha- decreases triglycerides- may increase LDL
What are the 4 approaches to lowering lipid levels?
- prevent intestinal absorption of cholesterol or bile acids
- decrease cholesterol synthesis–>increase LDL receptors–> increase LDL uptake
3, inhibit VLDL secretion –> decrease LDL production - upregulate lipoprotein lipase–> decrease trigs
Bile acid sequestrates are what? How do they increase uptake of LDL? Do they increase hepatic production of VLDL?
- large polymeric cationic exchange resins-insoluble in water
- increase uptake of LDL from up regulation of LDL receptors
- Yes
What bile sequestrates reduces hyperglycemia?
colesevalam- also has the less side effects and drug drug interactions.
What is niacins effect on bile production?
no effect
What can long term niacin treatment increase?
insulin resistnce
What CYP for lovastatin, simvastatin, atorvastatin? fluvastatin, rosuvastatin?
- CYP3A4
2. CYP2C9
How are HMG CoA reductase inhibitors enhanced absorption?
food
All statins undergo glycosylation and interact with?
gemfibrozil
What does grape juice inhibit?
CYP3A4 [lovastatin, simvastatin, atorvastatin]
PPAR activates polymerase and leads to what 4 things?
1 insulin sensitization
- anti-proliferative
- Anti-fibrotic
- anti-inflammatory
Fibric acids lowers VLDL and raises what?
HDL
What proteins do fibrin acids up regulate?
lipoprotein lipase, APO A-I, APO` A-II
When combining fibrin acids with status, what increased risk is there?
myopathy
Is ezetimibe a CYP450 substrate?
No
For high LDL cholesterol what classes do we use?
1.bile acid sequestrates
2. nicotinic acid or HMG inhibitor
can combine
For high LDL and trigs what do we use?
- weight loss and alcohol restriction
- niacin or gemfibrozil
- bile sequestrates or HMG inhibitors
[combination of the above increases risk of toxicity]
For high trig what do we use?
weight loss
gemfibrozil or nicotinic acid
For low HDL what do we use?
- diet exercise stop smoking
2. nicotinic acid or gemfibrozil
T-F– the combination of a statin and a bile acid binding resin is more effective than either alone?
True [decreases LDLs more and actually raises HDL]
