Hyperlipidaemias

Question 1

Via what receptor do monocytes uptake oxidised LDLs via?

Answer 1

Scavenger receptor SR-A

Question 2

How do statins result in decreased circulating LDLs?

Answer 2

Upregulation of hepatic LDL receptors leading to increased clearance of circulating LDLs.

Question 3

Give two additional benefits of statin therapy.

Answer 3

Improved vascular endothelial function - increased NO and VEGF and decreased endothelium

Stabilisation of the atherosclerotic plaque - decreased SMC proliferation and increased collagen

Question 4

What CYP are statins metabolised by?

Longer half life simvastatin or Atorvastatin?

Which one is a prodrug?

Answer 4

CYP 3A4

Atorvastatin - 30h vs 2hrs of simvastatin.

Simvastatin

Question 5

Give some ADRs of statins.

Answer 5

Transient serum transaminase elevation due to drug accumulation in the liver and subsequent damage.

Myalgia

Rhabdomyolysis

Nausea, GI disruption and headache

Question 6

Why was rosuvastatin withdrawn from use?

Second best efficacy?

Answer 6

Diabetes risk

Greatest efficacy out of statins though .

Atorvastatin.

Question 7

What is the primary prevention of statin dosage?

What qualifies you for primary prevention?

Secondary prevention?

Unless?

Answer 7

20mg Atorvastatin once daily

10 year CVD risk of >10% using Q risk

80mg “

CKD - 20mg dose instead.

Question 8

Why is simvastatin given before bed?

Why not Atorvastatin at this time?

Answer 8

LDL receptor synthesis greatest

Longer half life

Question 9

Name 3 fibrates.
Which one has extensive protein binding?
MOA fibrates.

Why do they elevated HDL?

Answer 9

fenofibrate
Ciprofibrate
Gemfibrozil

Fenofibrate

Actiavtion of PPARa - increased production of lipoprotein lipase - leads to TG decrease.

Increased apoAI and apoAII

Question 10

When are fibrates indicated?

ADRs.

Answer 10

Familial hypertriglyciridaemia (especially if HDL low who do not respond to NA)

Nausea and vomiting
Cholelithiasis (increase cholesterol content of bile)
Myositis
Warfarin potentiation

Question 11

Fibrate contraindications?

Answer 11

Hepatic/ Renal dysfunction

Pre-existing gallbladder disease

Question 12

MOA niacin.

Affect on other lipoproteins?

Answer 12

Inhibition of hormone sensitive lipase
Less FAs - means less FA can then be used by the liver to make VLDLs/ TGs

Increased HDL, decreased VLDL and LDL and decreased TGs. A

Question 13

ADRs?

Answer 13

Flushing (niacin induced prostaglandin release)
Gout/ hyperuricaemia (competes for excretion)
Hepatotoxicity
Headache
Itching

Question 14

How would you reduce headaches, itching and flushing?

Answer 14

Slow release preparations

Low dose aspirin 30 minutes prior (lowers PG synthesis)

Question 15

MOA ezetimibe.

ADRs?

Answer 15

Inhibition of NCPC1L1 transporter in small intestinal mucosa reducing cholesterol absorption. Less cholesterol to liver means more receptors and more clearance of LDLs.

few and mild
headache, abdominal pain and diarrhoea

Question 16

Why is the fact that ezetimibe undergoes enterohepatic circulation good?

Answer 16

It is a pro-drug that gets converted to ezetimibe glucoronide which is more efficacious

Question 17

What are you aiming for in secondary prevention?

Answer 17

Aim for 2mmol LDL-C

Or total 4mmol/L

Question 18

Name an effective combination therapy?

Answer 18

Statin + ezetimibe

Question 19

Name two monoclonal antibodies that can be used in hyperlipidaemia usage?

Answer 19

Alirocumab
Evolocumab

AliroEvolo
EliroEvolo

Question 20

Give some non prescription options.

Answer 20

Plant sterols (LDL lowering effects)
Fish oils
Fibre
Vitamin C/E

Question 21

Why do they not work with ezetimibe?

How do plant sterols work?

Answer 21

Similar structure and therefore compete for absorption

Because ezetimibe decreases absorption of cholesterol and hence would decrease the absorption of plant sterols also

Question 22

Affect of alcohol on lipid profile.

Answer 22

increased HDL and but also increased TGs.