Hyperlipidaemia

Question 1

Where and how is cholesterol synthesised?

Answer 1

Synthesised in the liver via the mevalonate pathway.

Question 2

What is the rate limiting enzyme in the cholesterol synthesis pathway?

Answer 2

HMG-CoA reductase - RLE in mevalonate pathway.

Question 3

What is the paradox effect of cholesterol on the cell membrane?

Answer 3

At high temperatures, it restrains movement and prevents membrane from melting.
At low temperatures, it prevents stiffness and prevents membrane from freezing.

Question 4

What is familial hyperlipidaemia? Name 3 physical signs.

Answer 4

Early development of atherosclerosis due to genetic variant in apolipoproteins.
Corneal arcus, xanthelasma, xanthoma.

Question 5

Name 2 statins.

Answer 5

Atorvastatin

Simvastatin

Question 6

What is the MOA of statins?

Answer 6

Competitively inhibits HMG-CoA reductase, the RLE in the mevalonate pathway that produces cholesterol.
Also increases expression of hepatic LDL receptors - increases LDL clearance.

Question 7

What time of day should statins be taken?

Answer 7

Just before bed, since LDL receptor synthesis is highest at this time - increases clearance of LDL and increases effectiveness.

Question 8

What needs to happen to simvastatin for it to become active?

Answer 8

Undergoes first pass metabolism to produce active metabolites (it’s a prodrug).

Question 9

Name some side effects/ADRs of statins.

Answer 9

• myalgia
• rhabdomyolysis
• GI disruption
• nausea
• headache
• elevated serum transaminase - due to liver injury

Question 10

Name some ways in which statins reduce risk of CVD.

Answer 10

• stabilisation of atherosclerotic plaques
• anti-inflammatory
• antioxidant

Question 11

Name a fibric acid derivative used as a lipid lowering drug.

Answer 11

Fenofibrate

Question 12

What is the MOA of fibric acid derivatives?

Answer 12

Activates the transcription factor PPAR-alpha, which regulates expression of lipoprotein lipase gene (RLE for hydrolysis of triglycerides) - decreases triglyceride.
Increases LDL affinity for its receptor - decreases LDL.

Question 13

Name some contraindications for lipid lowering drugs.

Answer 13

Hepatic or renal dysfunction (as most of them cause hepatotoxicity).

Question 14

Name some side effects of fibric acid derivatives.

Answer 14

• GI upset
• gall stones
• myosotis (inflammation of muscles)
• abnormal LFTs

Question 15

What drug does fibric acid derivatives interact with?

Answer 15

Warfarin - causes warfarin potentiation (increases effects of warfarin).

Question 16

Name a nicotinic acid drug that is used for lipid lowering.

Answer 16

Niacin

Question 17

What is the MOA of niacin?

Answer 17

Reduces fatty acid supply and therefore triglyceride synthesis.

Question 18

Name a cholesterol absorption inhibitor.

Answer 18

Ezetimibe

Question 19

What is the MOA of cholesterol absorption inhibitors?

Answer 19

Act at brush border of small intestine mucosa to inhibit NCPC1L1 transporter and decrease cholesterol absorption.
Increases hepatic LDL receptor expression.

Question 20

Name some side effects of nicotinic acid.

Answer 20

• flushing, itching
• headache
• GI disturbance
• hepatotoxicity

Question 21

What type of drug is ezetimibe?

Answer 21

Prodrug.

Question 22

Name some side effects of cholesterol absorption inhibitors.

Answer 22

• headache

- abdo pain, diarrhoea

Question 23

Which of the lipid lowering drugs is a useful combination with a stain for patients who can only tolerate a low dose statin?

Answer 23

Ezetimibe - cholesterol absorption inhibitor.

Question 24

Which drugs are commonly used for familial hypercholesterolaemia?

Answer 24

Fibric acid derivatives

Nicotinic acid

Question 25

What is the MOA of monoclonal antibodies when used as lipid lowering drugs?

Answer 25

PCSK9 inhibitors - inhibit degradation of LDL receptor - increases LDL clearance.

Question 26

Name 2 monoclonal antibodies used as lipid lowering drugs.

Answer 26

Alirocumab

Evolocumab

Question 27

Name some non-prescription options for high cholesterol.

Answer 27

Fish oils
Fibre
Vitamins C and E
Alcohol in small amounts - increases HDL cholesterol