agents used to treat hyperlipidemias Flashcards
hyperlipidemia
defect in lipid transport system that provides cholesterol and triglycerides to the cell.
hyperlipidemia leads to what
increase risk for coronary artery disease
increase risk of plaque formation in vascular
increase risk of pancreatits
increase risk of xanthoma
LDL stands for what
low density lipoprotein
how much LDL should you have
<100 mg/DL
secondary hyperlipoproteinemias
environmental causes
alcholoism- cirrhosis
diabetes- nephrosis
primary hyperlipoproteinemias.
genetic abnormalities decrease in lipoprotein lipase abnormal LDL receptors overproduction of VLDL decrease in HDL synthesis
treatment of hyperlipidemias
non-pharmacologic- diet, weight loss, aerobic exercise, stop smoking
also pharmacologic
decreasing fats in diet = decrease in what
cholesterol
pharmacologic treatment of hyperlipidemias
decrease production of lipoproteins
decrease absorption
increase removal of lipoproteins
(all effective with oral admin)
what is the most effective LDL lowering agent?
HMG CoA reductase inhibitors- lovastatin, “statin”s
lovastatin mech of action
prodrug
HMG CoA reductase- rate limiting step in cell synthesis of cholesterol
if cells can’t make any of their own cholesterol what happens?
find another way to get more LDL- increase LDL receptors of the cell = increase in LDL uptake (25%- 60%).
SE of lovastatin
- myositis (muscle pain) -> rhabdomyolysis (total breakdown of muscle)
- liver toxicity
- teratogenic pregnancy category X
- some memory loss
fats go into the gut and come out as _____ containing _____ and _____
chylomicrons, triglycerides, cholesterol
fate of chylomicrons
- lipoprotein lipase convert to free fatty acids that go to the cell
- remnants go to liver
chylomicrons remnants in the liver and do 2 things
- bind with apolipoprotein B and make VLDL
2. relased from liver as bile acids into the gut
liver also produces _____ that is ultimately reabsorbed by it
HDL
fate of VLDL
lipoprotein lipase takes of triglycerides = IDL,
Lplipase takes off more stuff = LDL
LDL is major carrier of what
cholesterol
fate of LDL
- oxidized and taken up by macrophages and deposited on arterial lining
- bind to LDL receptors on cell membrane where its converted to cholesterol
another way to make cholesterol in the cell
HMG CoA reductase
what is niacin?
vitamin B3
mechanism of action of niacin
- inhibits an enzyme essential for VLDL synthesis
2. bind to receptor that decreases VLDL synthesis
T/F niacin is best increaser of HDL
True
ultimately niacin increases what and decreases what
increases HDL, decrease VLDL
SE of niacin
cutaneous flushing “red face”
itching
increase uric acid-gout
increase incidence of diabetes
drugs that bing to bile acid
cholestyramine
colestipol
coleselevam
mech of action of bile acid binding resins
irreversibly bind to bile acids in gut causing them to be excreted with their cholesterol
outcome of taking bile acid binding agents
decreases circulating cholesterol
increases LDL receptors
do you have to take a lot of this drug to be effective?
yes 5-30g a day
SE of bile acid binding resins
no systemic cuz too big to be absorbed
can bind to acidic drugs like oral anticoagulants and digoxin
decrease absorption of fat soluble vitamins
nausea
agents that decrease cholesterol absorption by the intestines
SOOE Sitostanol orlistat olestra ezetimibe
ezetimibe
blocks cholesterol transporter
sitostanol
looks like cholesterol, blocks uptake
orlistat
inhibits GI, pancreatic lipase, decreases fat absorption in gut, major problem is loose stools
fibrates
best triglyceride lowering agents, bind to PPAR
fibrate drugs
gemfibrozil, fenofibrate
mech. of action of fibrates
increase transcription of lipoprotein lipase- decrease in triglycerides and VLDL
what can you not take with fibrates
warfarin- displaces it.
omega 3 fatty acids
decrease triglyercide synthesis, by inhibiting enzymes
omega 3 FA drug
icosapent
lomitapide
inhibits assembly of VLDL in liver
both enzyme and a transporter
SE of lomitapride
hepatoxicity
other hyperlipidemias
lomitapide
mipomersen
mipomersen
amhistase oligonucleotide
binds to RNA for APOb and prevents synthesis of APO
