Hyperlipidaemias

Question 1

Name some statins.

Answer 1

• Atorvastatin

- Simvastatin

Question 2

Mechanism of action of statins.

Answer 2

• Competitive inhibition of HMG-CoA reductase.

- Upregulation of LDL receptors so increased clearance of LDL occurs.

Question 3

Side effects of statins

Answer 3

• GI disruption
• Myalgia (therefore, check CPK levels)

Adjust dose based off side effects

Question 4

Avoid the use of statins in patients with:

Answer 4

• Renal impairment

- Pregnancy and breast feeding as cholesterol is required for development of fetus

Question 5

Contraindications of statins

Answer 5

• CYP3A4 inhibitors = amiodarone, diltiazem, macrolides, amlodipine is a weak inhibitor so can be given with high dose statin.
• Avoid grape fruit juice

Question 6

What is the first line statin prescribed and why?

Answer 6

• Atorvastatin because it reduces LDL levels greater for over the same period of time compared to simvastatin. Also has a longer half life.

Question 7

When should simvastatin be prescribed to be used for?

Answer 7

• Used at night because it has a shorter half life so it’s efficacy would be maximised as increased cholesterol production at night.

Question 8

What is treatment and allocation of dose based off to treat hyperlipidaemia?

Answer 8

• QRISK score >10% to see the risk of CVD in the next 10 years.

Question 9

Additional benefits of statin therapy?

Answer 9

• Decreased CVD risk
• Improved vascular endothelial function by increasing NO and VEGF and decreasing endothelin.
• Stabilisation of atherosclerotic plaque - decreased SMC proliferation and increased collagen.
• Improved Haemostasis by decreasing plasma fibrinogen, platelet aggregation and increasing fibrinolysis.
• Anti-inflammatory decreasing proliferation of inflammatory cells into plaque
• Antioxidant which reduces superoxide formation so less ROS = less foam cell production = less fatty streak production.

Question 10

Name a fibrates and it’s mechnism of action

Answer 10

• Fenofibrate
• Actives PPAR alpha which regulates gene expression - increased LPL expression.
• Increased FA brought to liver and increased TAG in plasma.

Question 11

Side effects of fibrates.

Answer 11

• Cholelithiasis As fibrates decrease bile acid excretion

- Myositis

Question 12

Contraindication of fibrates

Answer 12

• Warfarin - gets potentiated so increased bleeding.

Question 13

What are fibrates co-prescribed with?

Answer 13

• Statin

Question 14

Name a cholesterol absorption inhibitor

Answer 14

• Ezetimibe

Question 15

Mechanism of action of Ezetimibe

Answer 15

• Inhibits NPC1L1 in brush border of small intestine resulting in decreased absorption of cholesterol by 50%.

Question 16

Describe the metabolism of cholesterol absorption inhibitors.

Answer 16

• They are pro-drugs that get activated in the liver and remain in the entero-hepatic circulation.
• Since it remains in the GI, very few ADRs.

Question 17

Side effects of cholesterol absorption inhibitors.

Answer 17

• Abdo pain

- GI upset

Question 18

Avoid the cholesterol absorption inhibitors in patients with:

Answer 18

• Hepatic failure

Question 19

Which prescription regime will potentiate the effect of cholesterol absorption inhibitors?

Answer 19

• If it is co-prescribed with a statin at a low dose = decreased CVD more than a statin would alone.

Question 20

Name PCSK9 inhibitors.

Answer 20

• Alirocumab

- Evolocumab

Question 21

Mechanism of action of PCSK9 inhibitor

Answer 21

• Prevents LDL receptor internalisation and lysosomal degradation of the receptor. So increased LDL receptor expression = increased clearance or LDL from plasma.

Question 22

Why are PCSK9 inhibitors not prescribed more frequently?

Answer 22

• They are an expensive depo injection.