20 - Antihyperlipidemics Flashcards
most dense =
HDL
the least dense would be a chylomicron
dietary triglycerides and cholesteryl esters
chylomicron
endogenous triglycerides and cholesteryl esters
VLDL
cholesteryl esters and endogenous triglycerides
IDL
apoprtns associated with chylomicron
B-48
C
E
A
apoprtns associated with VLDL
C
B-100
E
apoprtns associated with LDL
B-100
apoprtns associated with HDL
A-I A-II C E D
3 roles of lipoprtns
- serve as cofactors for enzymes involved in lipoprtn metabolism
- serve as ligands for receptors
- structual stabillity of lipoprtns
Chylomicron metabolism
- nascent TAG rich chylomicrons with apoB48 leave the small intestine
- Apo C and Apo E added to chylomicron from HDL
- lipoprtn lipase degrades TAG in CM at adipose tissue
- Apoc C is returned to HDL
- CE rick CM remnant bind through apoE to receptors on liver where endocytosed
what activates lipoprtn lipase?
apo C
metabolism of hepatic origin lipoprtns
- liver secretes nascent TAG rich VLDLs with Apo B100
- Apo C and Apo E transferred to VLDL from HDL
- Liportn lipase activated by apoC degrades TAG in VLDL
- Apo C and Apo E returned to HDL (NOW AN IDL)
- LDL binds to specific receptors and are endocytosed
the only place where cholesterol can be eliminated
liver
___ of bile acids/salts are excreted in feces daily
5%
95% reabsorbed and returned to liver
accepts excess cholesterol from peripheral tissues
HDL
HDL is transported to the liver where it binds to SRB1 through ApoA and CE are selectively delivered to hepatocytes
what enzyme turns a nascent HDL into a CE full mature HDL
LCAT
lecithin:cholesterol acyltransferase
what apoprtn activates LCAT
apoA-I
which apoprtn is a cofactor for lipoprtn lipase
Apo C-II
Major goals of clinical management of dyslipidemia
- prevent acute pancreatitis
(severe hypertriglyceridemia) - preventionof cardiovascular disease (reduce LDL reduces CVD risk)
cause primary chylomicronemia
decreased lipoprtn lipase activity
manifestation primary chylomicronemia
increased chylomicrons/VLDL
cause familial hypertriglyceridemia
impaired removal of VLDL and or chylomicrons
manifestation of familial hypertriglyceridemia
increased VLDL and chylomicrons
cause familial combined hyperliproteinemia
increased VLDL production and high conversion of VLDL to LDL
manifestation of familial hyperlipoproteinemia
increased VLDL and LDL
cause familial dysbetalipoproteinemia
decreased cleareance of VLDL IDL and chylomicron remnant because of a dysfunction or absence of apoE
manifestation of familial dybetalipoproteinemia
increased IDL and chylomicrons
cause familal hypercholesterolemia
LDLR impairments, high fat diet, inactivity
manifestation of familial hypercholesterolemia
increased LDL
cause familal ligand-defective apoB
mutation in apoB100 resulting in impaired endocytosis of LDL
manifestation of familal ligand-defective apoB
increased LDL
present in 20% of individuals who get coronary heart disease under 60
familial combined hyperlipidemia – liver overproduces VLDL
MOA gemfibrozil and fenofibrate
PPAR actiavtor
- decreases plasma triglycerides
- increases plasma HDL (increased reverse cholesterol transport)
- increased oxidation of fatty acids
MOA cholestyramine
colestipol
colaevelam
bidn to bile acids and bile salts in the intestine
effects of bile acid-binding resins
decreased LDL but increased TAG
drug of choice to lower cholesterol in children and women who are pregnant or lactating
bile acid sequestrants
side effects of bile acid binding resins
bloating and constipation
how does niacin reduce both triglycerides and cholesterol?
- reduces hormone sensitive lipase to reduce FFA in plasma –> decreased VLDL and LDL
- also increases plasma HDL levels
which enzyme does niacin target to decrease FFA?
hormone sensitive lipase
side effect of niacin is reduced by what
flushing and itching can be reduced by pretreatment with NSAID
what statin is safest to combine with niacin?
fluvastatin
highest risk is lovastatin
inhibitor of cholesterol absorption
ezetimibe
blocks uptake of dietary cholesterol and reabsorption of cholesterol excreted in bile
what enyme does ezetimibe target?
niemann-pick C1 like prtn
most potent statins
atorvastatin and rosuvastatin
least = fluvastatin
statins aka
HMG CoA reducatase inhibitors
decreases CE in cell, causing uptake of LDL from the blood
indications for statins
elevated LDL
CVD
elevated CVD risk
which drug would be used for treatement of primary chylomicronemmia?
fibrates: gemfibrozil or fenofibrate
would also be used for familial dysbetaliprotenemia
what drugs would be used to treat familial ligand-defective apoB
statins or ezetimibe
