Chapter 19: Cholesterol and Lipoprotein Synthesis Flashcards
MOA of the “statins?” What is the result of administering?
Inhibit HMG-coA reductase (RL step in cholesterol synthesis)
Decrease in LDL, increase HDL, decrease triglycerides
What is the least potent statin?
Fluvastatin
What are the two most potent statins?
Atorvastatin & rosuvastatin
How does inhibiting cholesterol synthesis decrease LDL?
A decrease in cholesterol causes up regulation of LDL receptors (SREBP2) so they express more –> more uptake of cholesterol from the plasma
MOA of cholestyramine?
Inhibits bile acid absorption - this prevents enterohepatic circulation of the bile acids –> causes more bile salts to be made –> cholesterol is then excreted more
LDL decreases
HDL increase
What are the first and second line treatments for lowering LDL? What are the effects (respectively) on triglycerides?
Statins
Bile acid absorption inhibitors (Cholestyramine, colesevelam, colestipol)
Stains decrease tryglycerides, but bile acid abs inhibitors INCREASE levels!
Ezetimibe MOA?
Decreases cholesterol transport form micelles into the enterocyte by inhibiting uptake through brush border protein NPC1L1
Modest LDL reduction
What should you use with ezetimibe? Why?
Use a statin to prevent compensatory cholesterol synthesis
What drugs increase ezetimibe levels?
cyclosporine & fibrates
Do not use ezetimibe in pts with ____??
active liver disease
persistently elevated liver fxn test (even when given w a statin)
How do fibrates work?
Agonists of PPAR alpha –> this will increase lipoprotein lipase –> increase FA uptake into cells and decrease plasma TGs
What are the fibrate drugs?
Gemfibrozil
Fenofibrate
Drug of choice for hypertriglyeridemia?
Fibrates
When combining a fibrate with a statin, what is there an increased risk of?
myopathy
Fibrates _____ warfarin levels?
increase
Niacin MOA?
Decreases hormone sensitive lipase in order to decrease FFAs going to the liver for TG synthesis
Niacin is the drug of choice for what?
Tx for low HDL
What is a side effect of niacin that occurs within the first few weeks of use? How can this be prevented?
Flushing
Pretreat with aspirin
Niacin does what to insulin sensitivity?
impairs
What omega-3-fatty-acids are used to tx hypertriglyceridemia?
Eicosapentaenoic acid
Docosehexanoic acid
How do omega 3 fatty acids lower TG levels?
regulate nuclear transcription factors (SREBP-1c and PPARalpha) to reduce TG synthesis
