Pharmacology: Lipid Metabolism

Question 1

two layers of lipoproteins

Answer 1

1. hydrophobic core (cholesterol and TAGs)

2. hydrophilic coat (phospholipids, cholesterol)

Question 2

four classes of lipoproteins

Answer 2

• HDL (apoA-I and apoA-II)
• LDL (apoB-100)
• VLDL (apoB-100)
• chylomicrons (apoB-48)

Question 3

role of apoB-containing lipoproteins

Answer 3

deliver TAGs to muscle for ATP and adipocytes for storage

Question 4

three stages in the lifecycle of apoB-containing lipoproteins

Answer 4

1. assembly
2. intravascular metabolism
3. receptor mediated clearance

Question 5

where are apoB-100 lipoproteins synthesised?

Answer 5

liver

Question 6

where are apoB-48 lipoproteins synthesised?

Answer 6

intestine (NPC1L1)

Question 7

how are chylomicrons and VLDLs activated?

Answer 7

apoC-II from HDL

Question 8

what does apoC-II facilitate?

Answer 8

binding of chylomicrons and VLDL to LPL

Question 9

what does LPL do?

Answer 9

hydrolyses TAGs

Question 10

receptor mediated clearance

Answer 10

remnants return to the liver

Question 11

why is LDL bad cholesterol

Answer 11

LDL ix oxidised to OXLDL in the artery which causes migration of monocytes which turn into macrophages and take up OXLDL and form foam cells to make a fatty streak, which stimulates proliferation of smooth muscle and deposition of collagen and formation of a plaque

Question 12

why is HDL good cholesterol?

Answer 12

it transfers excess cholesterol from plasma membrane to the liver which removes cholesterol from the body

Question 13

two classes of drugs that lower lipids

Answer 13

1. statins

2. fibrates

Question 14

examples of statins

Answer 14

simvastatin

atrovastatin

Question 15

what are statins first lines for?

Answer 15

reducing LDLs

Question 16

mechanism of action of statins

Answer 16

inhibits HMG-CoA which decreases LDL expression and clearance

Question 17

what are statins useless in

Answer 17

familial hypercholesterolaemia where LPL receptors are absent

Question 18

adverse of statins

Answer 18

myositis

rhabdoymyolosis

Question 19

examples of fibrates

Answer 19

bezafibrate

gemifibrozil

Question 20

what are fibrates first line for?

Answer 20

reducing TAGs

Question 21

mechanism of action of fibrates

Answer 21

agonists of the nuclear receptor PPAR-alpha which enhances transcription of LPL genes

Question 22

adverse of fibrates

Answer 22

myositis, rhabdomyolysis, GI symptoms, pruritus and rash

Question 23

two types of drugs that inhibit cholesterol absorption

Answer 23

• bile acid binding resins

- ezetimibe

Question 24

examples of bile acid binding resins

Answer 24

colestyramine
colestipol
colsevelam

Question 25

mechanism of action of bile acid binding resins

Answer 25

excretion of bile salts increased so there is decreased absorption of TAGs

Question 26

adverse of bile acid binding resins

Answer 26

GI tract irritation

Question 27

mechanism of action of ezetimibe

Answer 27

inhibits NPC1L1, reducing absorption of cholesterol

Question 28

adverse of ezetimibe

Answer 28

diarrhoea abdominal pain headaches