Antihyperlipidemics

Question 1

what is the lowest density lipoprotein?

Answer 1

chylomicron

Question 2

what are the roles of the apolipoproteins?

Answer 2

1. cofactors
2. ligands for receptors
3. structural stability

Question 3

what is the role of NPC1L1?

Answer 3

cholesterol uptake

Question 4

which drug inhibits the NPC1L1 enzyme?

Answer 4

ezetimibe

Question 5

what is the role of acetyl CoA cholesterol acyltransferase?

Answer 5

converts cholesterol to cholesterol ester

Question 6

what is the role of diglyceride acyltransferase?

Answer 6

converts monoglycerides to TGs

Question 7

where are chylomicrons associated with the B28 apoprotein?

Answer 7

intestine

Question 8

where do chylomicrons associate with apoC2 and apo3?

Answer 8

lymphatic system

Question 9

where are the chylomicrons broken down to TGs by lipoprotein lipase?

Answer 9

capillaries (via apoC2)

Question 10

what is the importance of apoE?

Answer 10

allows chylomicron remnants to be taken back up by liver

Question 11

what is the importance of apoB100 for VLDL particles?

Answer 11

ligand for LDL receptors (important for clearance of cholesterol from circulatory system)

Question 12

what is reverse cholesterol transport?

Answer 12

1. HDL accepts excess cholesterol from peripheral tissues
2. HDL is transported to liver where it binds SRB1 via apoA1 and cholesterol esters are selectively delivered to hepatocytes

Question 13

apoA1 is associated with which lipoproteins? what is its function?

Answer 13

1. HDL, chylomicrons

2. structural for HDL, activates LCAT, SRB1 ligand

Question 14

apoA2 is associated with which lipoproteins? what is its function?

Answer 14

1. HDL, chylomicrons

2. structural for HDL

Question 15

apoB48 is associated with which lipoproteins? what is its function?

Answer 15

1. chylomicrons, remnants

2. structural

Question 16

apoB100 is associated with which lipoproteins? what is its function?

Answer 16

1. VLDL, LDL, IDL

2. structural for above, ligand for LDL

Question 17

apoC2 is associated with which lipoproteins? what is its function?

Answer 17

1. chylomicrons, VLDL, HDL

2. COFACTOR FOR LIPOPROTEIN LIPASE

Question 18

apoE is associated with which lipoproteins? what is its function?

Answer 18

1. chylomicron, VLDL, IDL, HDL

2. ligand for LDL and remnant receptors

Question 19

what is the cause of primary chylomicronemia? how does it manifest?

Answer 19

1. decrease in lipoprotein lipase activity

2. increased chylomicrons, VLDL

Question 20

what is the cause of familial hypertriglyceridemia? how does it manifest?

Answer 20

1. impaired removal of VLDL and/or chylomicrons

2. increased VLDL (moderate), VLDL AND chylomicrons (severe)

Question 21

what is the cause of familial combined hyperlipoproteinemia? how does it manifest?

Answer 21

1. increased VLDL production by liver

2. increased VLDL, LDL

Question 22

what is the cause of familial dysbetalipoproteinemia? how does it manifest?

Answer 22

1. decreased clearance of VLDL, IDL, and chylomicrons due to dysfunction or absence of apoE
2. increased IDL chylomicrons

Question 23

what is the cause of primary familial hypercholesterolemia? how does it manifest?

Answer 23

1. LDLr impairments, high fat diet, inactivity

2. increased LDL

Question 24

what is the cause of familial ligand defective apoB? how does it manifest?

Answer 24

1. mutation in apoB100 - impaired endocytosis of LDL

2. increased LDL

Question 25

what do the fibrates do? what is the MOA?

Answer 25

1. activate PPAR receptor 2. increase plasma HDL, lower TGs 3. increase oxidation of fatty acids

Question 26

what are the fibrate drugs?

Answer 26

1. gemfibrozil | 2. fenofibrate

Question 27

the fibrates are good for what condition?

Answer 27

hypertriglyceridemia

Question 28

what are the bile acid binding resins?

Answer 28

1. cholestyramine 2. colesevelam 3. colestipol

Question 29

what do the bile acid binding resins do? what is the MOA?

Answer 29

1. soak up bile acids in intestine 2. liver makes more bile acids and uptakes cholesterol to do so 3. increases LDL receptors - decreases plasma LDL

Question 30

what does niacin do? what is the MOA?

Answer 30

1. decreases VLDL and LDL 2. increases HDL, decreases plasma free fatty acids which decreases VLDL synthesis by liver 3. may also decrease plasma plasminogen (anti-thrombosis)

Question 31

what are the side effects of niacin?

Answer 31

1. cutaneous flushing and itching | 2. hyperuricemia (gout susceptible)

Question 32

what is the main cholesterol uptake inhibitor drug? what is the MOA?

Answer 32

1. ezetimibe | 2. inhibits nieman pick C1 like protein

Question 33

how do the statins work? what is the MOA?

Answer 33

1. inhibits cholesterol synthesis 2. competitive inhibitor of HMG CoA reductase 3. increases concentration of LDLr in blood, hepatocytes, and extrahepatic sites

Question 34

what are the most potent statins?

Answer 34

atorvastatin and rosuvastatin

Question 35

what are the adverse effects of the statins?

Answer 35

1. liver failure 2. myopathy 3. contraindicated during pregnancy