Anti-dyslipidaemics Flashcards
Explain this picture?
Cholesterol is synthesised from acetyl coA.
Inhibiting HMG coA reductase could help prevent high cholesterol.
Which lipoprotein is protective? Which are atherlerogenic?
HDL=good.
LDL and IDL=bad.
Which apoproteins are in which lipoproteins?
ApoA and ApoB.
LDL and VLDL are associated with ApoB100 proteins.
What role does HDL have?
- Delivers cholesterol esters to livse and LDLs in plasma for peripheral delivery.
- Also plays a vital role in scavenging excess used cholesterol from peripheral tissues.
What are the 2 ways in which cells can obtain cholesterol?
Explain the process of LDL uptake from the plasma into cells?
What happens to the receptors after uptake?
What are the downstream effects (in the photo)?
Raised intracellular cholesterol has 3 effects:
1) Decreased activity of HMG CoA reductase.
2) activates acetyl coA:cholesterolacyltransferase (ACAT) to esterify free cholesterol into cholesterol ester that can be stored within the cell.
3) Inhibits the gene encoding for the LDL receptor, and therefore decreases further uptake of LDL.
What does an increase in plasma cholesterol put you at risk of?
Atherosclerosis and therefore CHD.
LDL makes it to the _____ of the _______ arteries.
This is then taken up by _________ and this turns them into _______ cells.
This then leads to cell __________ and matrix _________.
Intima of the elastic arteries.
Macrophages and turns them to foam cells.
cell growth and matrix degradation.
(the macrophages release even more cytokines which attract them to the intima).
Main causes of high cholesterol?
What is the most effective pharmacological intervention for dyslipidemia?
How do statins work?
They inhibit HMG-CoA reductase action. This means that hepatic de novo synthesis of cholesterol is inhibited. This increases the cells LDL-R (increase in LDL gene expression) removing LDL from circulation.
Why is a statin considered to have pleiotropic effects?
The decrease in hepatocyte cholesterol causes a lot of good downstream effects.
What is the statin which we need to know?
Atorvastatin.
How is atorvastatin removed from the body? (what major enzyme degrades it?)
What is the half life of atorvastatin and its active metabolites?
_____ impairment increases atorvastatin retention, _____ impairment has no major impact.
CYP3A4.
What is the example of the cholesterol uptake inhibitor and how does it work?
Ezetimibe
What are the main side effects of taking statins?
Myopathy and rhabdomyolysis.
Rhabdo can damage the kidneys and cause death.
What drugs have the potential to interact with statins and cause an increase in myopathy risk?
CYP3A4 inhibitor is the main one.
What are fibrates?
What an example of a fibrate that we need to know?
Bezafibrate: activates PPARalpha which causes an increase in fatty acid oxidation in muscles and liver plus lipogenesis in the liver.
Increases HDL,
Decreases VLDL, TG and LDL.
Explain how you could prevent this from happening?
Monoclonal antibody for enzyme which degrades the LDL receptor.
