20 - Antihyperlipidemics

Question 1

most dense =

Answer 1

HDL

the least dense would be a chylomicron

Question 2

dietary triglycerides and cholesteryl esters

Answer 2

chylomicron

Question 3

endogenous triglycerides and cholesteryl esters

Answer 3

VLDL

Question 4

cholesteryl esters and endogenous triglycerides

Answer 4

IDL

Question 5

apoprtns associated with chylomicron

Answer 5

B-48
C
E
A

Question 6

apoprtns associated with VLDL

Answer 6

C
B-100
E

Question 7

apoprtns associated with LDL

Answer 7

B-100

Question 8

apoprtns associated with HDL

Answer 8

A-I
A-II
C
E
D

Question 9

3 roles of lipoprtns

Answer 9

1. serve as cofactors for enzymes involved in lipoprtn metabolism
2. serve as ligands for receptors
3. structual stabillity of lipoprtns

Question 10

Chylomicron metabolism

Answer 10

1. nascent TAG rich chylomicrons with apoB48 leave the small intestine
2. Apo C and Apo E added to chylomicron from HDL
3. lipoprtn lipase degrades TAG in CM at adipose tissue
4. Apoc C is returned to HDL
5. CE rick CM remnant bind through apoE to receptors on liver where endocytosed

Question 11

what activates lipoprtn lipase?

Answer 11

apo C

Question 12

metabolism of hepatic origin lipoprtns

Answer 12

1. liver secretes nascent TAG rich VLDLs with Apo B100
2. Apo C and Apo E transferred to VLDL from HDL
3. Liportn lipase activated by apoC degrades TAG in VLDL
4. Apo C and Apo E returned to HDL (NOW AN IDL)
5. LDL binds to specific receptors and are endocytosed

Question 13

the only place where cholesterol can be eliminated

Answer 13

liver

Question 14

___ of bile acids/salts are excreted in feces daily

Answer 14

5%

95% reabsorbed and returned to liver

Question 15

accepts excess cholesterol from peripheral tissues

Answer 15

HDL

HDL is transported to the liver where it binds to SRB1 through ApoA and CE are selectively delivered to hepatocytes

Question 16

what enzyme turns a nascent HDL into a CE full mature HDL

Answer 16

LCAT

lecithin:cholesterol acyltransferase

Question 17

what apoprtn activates LCAT

Answer 17

apoA-I

Question 18

which apoprtn is a cofactor for lipoprtn lipase

Answer 18

Apo C-II

Question 19

Major goals of clinical management of dyslipidemia

Answer 19

• prevent acute pancreatitis
  (severe hypertriglyceridemia)
• preventionof cardiovascular disease (reduce LDL reduces CVD risk)

Question 20

cause primary chylomicronemia

Answer 20

decreased lipoprtn lipase activity

Question 21

manifestation primary chylomicronemia

Answer 21

increased chylomicrons/VLDL

Question 22

cause familial hypertriglyceridemia

Answer 22

impaired removal of VLDL and or chylomicrons

Question 23

manifestation of familial hypertriglyceridemia

Answer 23

increased VLDL and chylomicrons

Question 24

cause familial combined hyperliproteinemia

Answer 24

increased VLDL production and high conversion of VLDL to LDL

Question 25

manifestation of familial hyperlipoproteinemia

Answer 25

increased VLDL and LDL

Question 26

cause familial dysbetalipoproteinemia

Answer 26

decreased cleareance of VLDL IDL and chylomicron remnant because of a dysfunction or absence of apoE

Question 27

manifestation of familial dybetalipoproteinemia

Answer 27

increased IDL and chylomicrons

Question 28

cause familal hypercholesterolemia

Answer 28

LDLR impairments, high fat diet, inactivity

Question 29

manifestation of familial hypercholesterolemia

Answer 29

increased LDL

Question 30

cause familal ligand-defective apoB

Answer 30

mutation in apoB100 resulting in impaired endocytosis of LDL

Question 31

manifestation of familal ligand-defective apoB

Answer 31

increased LDL

Question 32

present in 20% of individuals who get coronary heart disease under 60

Answer 32

familial combined hyperlipidemia -- liver overproduces VLDL

Question 33

MOA gemfibrozil and fenofibrate

Answer 33

PPAR actiavtor - decreases plasma triglycerides - increases plasma HDL (increased reverse cholesterol transport) - increased oxidation of fatty acids

Question 34

MOA cholestyramine colestipol colaevelam

Answer 34

bidn to bile acids and bile salts in the intestine

Question 35

effects of bile acid-binding resins

Answer 35

decreased LDL but increased TAG

Question 36

drug of choice to lower cholesterol in children and women who are pregnant or lactating

Answer 36

bile acid sequestrants

Question 37

side effects of bile acid binding resins

Answer 37

bloating and constipation

Question 38

how does niacin reduce both triglycerides and cholesterol?

Answer 38

- reduces hormone sensitive lipase to reduce FFA in plasma --> decreased VLDL and LDL - also increases plasma HDL levels

Question 39

which enzyme does niacin target to decrease FFA?

Answer 39

hormone sensitive lipase

Question 40

side effect of niacin is reduced by what

Answer 40

flushing and itching can be reduced by pretreatment with NSAID

Question 41

what statin is safest to combine with niacin?

Answer 41

fluvastatin highest risk is lovastatin

Question 42

inhibitor of cholesterol absorption

Answer 42

ezetimibe blocks uptake of dietary cholesterol and reabsorption of cholesterol excreted in bile

Question 43

what enyme does ezetimibe target?

Answer 43

niemann-pick C1 like prtn

Question 44

most potent statins

Answer 44

atorvastatin and rosuvastatin least = fluvastatin

Question 45

statins aka

Answer 45

HMG CoA reducatase inhibitors decreases CE in cell, causing uptake of LDL from the blood

Question 46

indications for statins

Answer 46

elevated LDL CVD elevated CVD risk

Question 47

which drug would be used for treatement of primary chylomicronemmia?

Answer 47

fibrates: gemfibrozil or fenofibrate would also be used for familial dysbetaliprotenemia

Question 48

what drugs would be used to treat familial ligand-defective apoB

Answer 48

statins or ezetimibe