15 Hyperlipidaemia Pharmacology

Question 1

What causes Atherosclerosis?

Answer 1

LDL accumulation, which are oxidised and them absorbed by macrophage

Question 2

How can macrophage containing oxLDL cause a problem?

Answer 2

release growth factor, causing smooth muscle and connective tissue to proliferate. forms a fibrous cap over lipid cores

Question 3

What is the fibrous cap over lipid cores called, what can happen if it breaks?

Answer 3

atheromatous plaque

thrombosis

Question 4

What are the two lipid pathways?

Answer 4

exogenous

endogenous

Question 5

How does the exogenous pathway work?

Answer 5

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

Question 6

What are the two parts of the endogenous pathway, how is it different to the exogenous pathway?

Answer 6

hepatic
extrahepatic
(independent of the GI tract)

Question 7

What does the liver do with VLDL and CE?

Answer 7

packages them in VLDL things, delivers TG to blood, and takes back LDL’s to the liver

Question 8

What proportion of circulating cholesterol is LDL, and what is it used for?

Answer 8

60-70%

membrains, steroids, and bile acids

Question 9

How do we treat high levels of HDL’s and low levels of LDL’s differently?

Answer 9

high LDL’s - drugs

low HDL’s - lifestyle

Question 10

What are the different types of hyperlipidaemia?

Answer 10

primary (IIa, IIb)

secondary

Question 11

What is the difference between primary IIa and IIb?

Answer 11

IIa - high LDL

IIb - high LDL and high VLDL

Question 12

what might cause secondary hyperlipidaemia?

Answer 12

metabolic disorders
alcoholism
diabetes

Question 13

What are the 7 pharmacological interventions for hyperlipiaemia?

Answer 13

statins
PCSK9 inhibitors
fibrates 
bile acid binding resins
ezetimibe
nicotinic acid
fish oil

Question 14

How do statins work?

Answer 14

inhibit HMG CoA reductase, which is the rate determining dtep enzyme for hepatic cholesterol synthesis

Question 15

Roughly, what is the function of LDL’s and HDL’s?

Answer 15

LDL’s - transport cholesterol around the body (bad)

HDL’s - take cholesterol back to liver (good)

Question 16

How do PCSK9 inhibitorswork?

give one example?

Answer 16

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

Question 17

How do fibrates work? name 2 examples

Answer 17

activate nuclear receptors, increasing transcription;
increases HDL’s
increased uptake of LDL
bezafibrate, Gemfibrozil

Question 18

How do bile acid binding resins work?

Answer 18

bowel loses cholesterol and bile acid, increased LDL receptors as feedback control, decreasing LDL levels
Cholestyramine, colestipol

Question 19

how does exetimibe work?

Answer 19

inhibits cholesterol trasnporter protein NPC1L1, limiting absorption

Question 20

How does nicotinic acid work?

Answer 20

decreased TG synthesis (hence decreased VLDL’s and LDL’s)

high HDL’s

Question 21

How does fish oil work?

Answer 21

decreasing clotting, not sure how