Hyperlipidaemias

Question 1

What is the pathophysiology of atherosclerosis?

Answer 1

1. Endothelial injury (^BP/hyperlipidaemia/smoking).
2. LDL deposit in intima or if LDL receptors become saturated.
3. LDL oxidised by macrophages.
4. Foam cells made.
5. Foam cells accumulate.
6. Smc from the media migrate.
7. Fatty streak formed.
8. Fibrous cap form over top.
9. Centre of plaque die and necrosis occur.
10. Dead cell release cholesterol so cholesterol clefts seen.

Question 2

Give 2 examples of statins.

Answer 2

Atorvastatin and Simvastatin.

Question 3

How do statins work?

Answer 3

1. Competitive inhibition of HMG-CoA reductase: inhibit cholesterol synthesis in hepatocytes.
2. Decrease production of LDL and increase LDL receptor synthesis (taken up rather than oxidised).

Question 4

What are the other benefits of statins?

Answer 4

Improve vascular endothelial function, stabilise plaque, prevent thrombus formation, anti-inflammation and anti-oxidation.

Question 5

What are the adverse side effects of statins?

Answer 5

1. Myalgia.
2. Rhabdomyolysis.
3. GI disruption.
4. Nausea.
5. Headaches.

Question 6

When are statins used?

Answer 6

First line treatment for elevated cholesterol with increased CVD risk.
Used post-MI to reduce chance of another event.

Question 7

How do Fibric Acid Derivatives treat hyperlipidaemias?

Answer 7

Increase production of lipoprotein lipase which allows chylomicrons to release their TAG into muscle cells.
Reduce TAG.
Increase HDL.

Question 8

Give an example of a fibric acid derivative.

Answer 8

Fenofibrate.

Question 9

How are fibric acid derivatives used clinically?

Answer 9

Co-prescribed with statin as they act at a different site.

Used when there is hyperlipidaemia with low HDL.

Question 10

Describe the pharmacokinetics of fibric acid derivatives (fenofibrate).

Answer 10

Fenofibrate is widely distributed and bound to albumin.

Question 11

What are the side effects of fibric acid derivatives?

Answer 11

1. GI upset.
2. Cholelithiasis.
3. Myositis.
4. Abnormal LFT.

Question 12

What are the contraindications to use of fibric acid derivatives?

Answer 12

Do not use in patients with hepatic or renal dysfunction or pre-existing gallbladder disease.

Question 13

How do nicortinic acid drugs work to treat hyperlipidaemia?

Answer 13

Reduce VLDL levels and LDL levels and increase HDL levels.

They are antilipolytic so reduce fatty acid supply and TAG synthesis.

Question 14

Give an example of a nicotinic acid.

Answer 14

Niacin.

Question 15

How do Cholesterol Absorption Inhibitors work at treating hyperlipidaemia?

Answer 15

1. Act at brush border of SI mucosa, inhibit NCP1L1 transporter: decrease absorption of cholesterol by gut.
2. Increase hepatic LDL-R.
3. Reduce LDL.

Question 16

Give an example of a Cholesterol Absorption Inhibitor.

Answer 16

Ezetimibe.

Question 17

What are the side effects of CAI?

Answer 17

1. Headache.
2. Abdominal pain.
3. Diarrhoea.

Question 18

Identify and describe a new development in hyperlipidaemia treatment.

Answer 18

Alirocumab: stop the recycling/destruction of the LDL-R when it is being internalised with LDL via receptor mediated endocytosis.

Question 19

What are resins?

Answer 19

Bile acid sequesters that stop bile acids being recycled and thus mean more cholesterol is used to make bile.

Question 20

Give an example of a resin.

Answer 20

Cholestyramine.

Question 21

Why are resins not used much anymore?

Answer 21

They increase TAG.