Lecture - Pharmacology (Statins and Fibrates)

Question 1

General background:

1. What’re some risk factors for getting high LDL and low HDL?
2. What’s the enzyme called that’s involved in the second step of the biosynthesis of cholesterol?
3. LDL transports majority of cholesterol in plasma:
   - what’re the two ways cells can obtain cholesterol?
   - so cellular cholesterol can be regulated by adjusting/targetting what two things?
4. What apolipoprotein binds to the LDL receptors? Then what happens to the receptor and the LDL?
5. When cholesterol is formed in the cell by hydrolysing the lipoproteins (and free aa’), what three things does it do?
6. If you increase plasma cholesterol, what happens to your risk of ahterosclerosis? Explain what happens between arteries and LDL
7. What sort of diet and deficiency in something is atherosclerosis associated with?
8. What does turbulent flow or hypertension do?
9. So how low should LDL-cholesterol be lowered?
   - what’s primary and secondary prevention?
10. Before you get to pharmaology, what else is used to help riase HDL-C, lower LDL-C, lower TG, lower glucose, insulin and blood pressure levels?

Answer 1

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Question 2

Anti-hyperlipidaemics:

1. What’re two endogenous CE attenuators?
2. What’s one exogenous CE uptake inhibitors?

Answer 2

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Question 3

Statins:

0. What’s an example of a statin?
1. It’s most effective treatment for dyslipidaemia. It’s described as a p_______ drug - what does this mean?
2. What’s the MOA of atorvastatin?
   - What are the results of using statins?
3. What’re the pleiotropic effects of statins? Go onto slide 31 to know this
4. What’s this pleiotropic effect of statin PPAR-alpha activation?
5. Atorvastatin PK:
   - delivery method?
   - bioavilability?
   - metabolism?
   - half life?
   - hepatic impairment?
6. What’s a major adverse reaction with statins? Explain it with slide 37
   - what may it elevate and when should you avoid it?
7. What’re drugs with potential to interat with statins to increase myopathy risk?

Answer 3

4. So statins reduce the inflammatory process by exerting anti-inflam effects by preventing binding transcription factor of NFkB to DNA target. This activates peroxisome proliferator-activated receptors which will inhibit uptake of LDL by macrophage to reduce C-reactive protein release. It will increase endogenous NO release to produce systemic vasodilation and many other effects associated with this pleiotropic drug class.

Question 4

Fibrates:

1. They’re known as _______ activators
2. What’s an example?
3. Effective at reeducing and increasing levels of what?
4. What’s the MOA of fibrates?

Answer 4

4. So they increase FA oxidation in muscles and liver and lipogenesis in the liver. SO fibrates bind to and activate the PPAR-alpha which is a nuclear receptor expressed in hepatocytes, skeletal muscles, macrophages and the heart. This activates peroxisome proliferator rersponse elements (PPREs) in the promotor regions of specific genes producing specific protein translation. They also lower LDL levels by PPAR-alpha shift in hepatocyte metabolsim towards FA-oxidation. SLide 39 has the effects

Question 5

Cholesterol uptake inhibitors:

1. What’s an example?
2. So how does it work?

Answer 5

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