15 Hyperlipidaemia Pharmacology Flashcards
What causes Atherosclerosis?
LDL accumulation, which are oxidised and them absorbed by macrophage
How can macrophage containing oxLDL cause a problem?
release growth factor, causing smooth muscle and connective tissue to proliferate. forms a fibrous cap over lipid cores
What is the fibrous cap over lipid cores called, what can happen if it breaks?
atheromatous plaque
thrombosis
What are the two lipid pathways?
exogenous
endogenous
How does the exogenous pathway work?
normal lipid absorption, absorbed and turned into chylomicrons, TG’s hydrolysed by lipoprotein lipase. Free fatty acids then go into the blood and the chylomicron remnants for to the liver
What are the two parts of the endogenous pathway, how is it different to the exogenous pathway?
hepatic
extrahepatic
(independent of the GI tract)
What does the liver do with VLDL and CE?
packages them in VLDL things, delivers TG to blood, and takes back LDL’s to the liver
What proportion of circulating cholesterol is LDL, and what is it used for?
60-70%
membrains, steroids, and bile acids
How do we treat high levels of HDL’s and low levels of LDL’s differently?
high LDL’s - drugs
low HDL’s - lifestyle
What are the different types of hyperlipidaemia?
primary (IIa, IIb)
secondary
What is the difference between primary IIa and IIb?
IIa - high LDL
IIb - high LDL and high VLDL
what might cause secondary hyperlipidaemia?
metabolic disorders
alcoholism
diabetes
What are the 7 pharmacological interventions for hyperlipiaemia?
statins PCSK9 inhibitors fibrates bile acid binding resins ezetimibe nicotinic acid fish oil
How do statins work?
inhibit HMG CoA reductase, which is the rate determining dtep enzyme for hepatic cholesterol synthesis
Roughly, what is the function of LDL’s and HDL’s?
LDL’s - transport cholesterol around the body (bad)
HDL’s - take cholesterol back to liver (good)
How do PCSK9 inhibitorswork?
give one example?
stop PCSK9 from binding to LDL receptors on hepatocytes and breaking them down (therefore, it increases the number of LDL receptors around to reduce blood LDL levels)
Alirocumab
How do fibrates work? name 2 examples
activate nuclear receptors, increasing transcription;
increases HDL’s
increased uptake of LDL
bezafibrate, Gemfibrozil
How do bile acid binding resins work?
bowel loses cholesterol and bile acid, increased LDL receptors as feedback control, decreasing LDL levels
Cholestyramine, colestipol
how does exetimibe work?
inhibits cholesterol trasnporter protein NPC1L1, limiting absorption
How does nicotinic acid work?
decreased TG synthesis (hence decreased VLDL’s and LDL’s)
high HDL’s
How does fish oil work?
decreasing clotting, not sure how
