Pharmacology: Lipid Metabolism Flashcards
two layers of lipoproteins
- hydrophobic core (cholesterol and TAGs)
2. hydrophilic coat (phospholipids, cholesterol)
four classes of lipoproteins
- HDL (apoA-I and apoA-II)
- LDL (apoB-100)
- VLDL (apoB-100)
- chylomicrons (apoB-48)
role of apoB-containing lipoproteins
deliver TAGs to muscle for ATP and adipocytes for storage
three stages in the lifecycle of apoB-containing lipoproteins
- assembly
- intravascular metabolism
- receptor mediated clearance
where are apoB-100 lipoproteins synthesised?
liver
where are apoB-48 lipoproteins synthesised?
intestine (NPC1L1)
how are chylomicrons and VLDLs activated?
apoC-II from HDL
what does apoC-II facilitate?
binding of chylomicrons and VLDL to LPL
what does LPL do?
hydrolyses TAGs
receptor mediated clearance
remnants return to the liver
why is LDL bad cholesterol
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
why is HDL good cholesterol?
it transfers excess cholesterol from plasma membrane to the liver which removes cholesterol from the body
two classes of drugs that lower lipids
- statins
2. fibrates
examples of statins
simvastatin
atrovastatin
what are statins first lines for?
reducing LDLs
mechanism of action of statins
inhibits HMG-CoA which decreases LDL expression and clearance
what are statins useless in
familial hypercholesterolaemia where LPL receptors are absent
adverse of statins
myositis
rhabdoymyolosis
examples of fibrates
bezafibrate
gemifibrozil
what are fibrates first line for?
reducing TAGs
mechanism of action of fibrates
agonists of the nuclear receptor PPAR-alpha which enhances transcription of LPL genes
adverse of fibrates
myositis, rhabdomyolysis, GI symptoms, pruritus and rash
two types of drugs that inhibit cholesterol absorption
- bile acid binding resins
- ezetimibe
examples of bile acid binding resins
colestyramine
colestipol
colsevelam
mechanism of action of bile acid binding resins
excretion of bile salts increased so there is decreased absorption of TAGs
adverse of bile acid binding resins
GI tract irritation
mechanism of action of ezetimibe
inhibits NPC1L1, reducing absorption of cholesterol
adverse of ezetimibe
diarrhoea
abdominal pain
headaches
