Hyperlipidaemias

Question 1

What is the mechanism of action of statins?

Answer 1

• competitive inhibition of HMG-CoA reductase
• limits conversion of HMG-CoA to mevalonate > less cholesterol made
• up regulation of hepatic LDL receptors
• increased clearance of circulating LDL

Question 2

What is cholesterol essential for?

Answer 2

• Membrane integrity
• Production of steroid horomones, bile acids + vitamin D

Question 3

Types of lipoproteins

Answer 3

Chylomicrons
VLDL
IDL
LDL
HDL

Question 4

Function of Chylomicron

Answer 4

Transports dietary TAGs from intestines to tissue

Question 5

Function of VLDL

Answer 5

Transport liver synthesised TAGs to adipose tissue for storage

Question 6

Function of IDLs

Answer 6

Transport liver synthesised cholesterol to tissues

Question 7

Function of LDLs

Answer 7

Transport liver synthesised cholesterol to tissue

Question 8

Function of HDLs

Answer 8

Transports excess tissue cholesterol to liver for disposal as bile salts

Question 9

What are the uses of stains?

Answer 9

Hypercholesterolaemia
Prevention of cardiovascular disease
Reduce risk of atherosclerosis

Question 10

What are the adverse effects of statins?

Answer 10

• GI disruption > nausea, constipation + diarrhoea
• headache
• diffuse muscle pain
• increased liver enzymes
• Rhabdomyolysis (rare)

Question 11

What are contraindications of statins?

Answer 11

Renal or hepatic impairment
Pregnancy or breastfeeding

Question 12

What are the important drug drug interactions of stains?

Answer 12

Amlodipine
Drugs which inhibit CYP3A4: amiodarone, Macrolides (e.g. clarithromycin)

Question 13

What effects do statins have that contribute towards reduction in cardiovascular disease risk?

Answer 13

• reduce cholesterol
• improved vascular endothelial function
• stabilising of atherosclerotic plaques
• improved haemostasis
• anti-inflammatory + antioxidant
  = reduction in cardiovascular disease risk

Question 14

Examples of statins

Answer 14

Atorvastain
Rosuvastatin
Simvastatin

Question 15

What is the suffix of stains?

Answer 15

-statin

Question 16

Why may a simvastatin be suggested to be taken at night time?

Answer 16

• Most cholesterol is made at night
• Simvastatin has a short half life
• Can have the ‘best aciton’

Question 17

Why shouldn’t you have grapefruit juice whilst taking statins?

Answer 17

Grapefruit inhibit CYP3A4 causes higher levels of stain in blood

Question 18

Difference between primary and secondary prevention of CVD

Answer 18

• primary prevention: for people at high risk of CVD
• secondary prevention: for people who already have CVD

Question 19

What is the nocebo effect?

Answer 19

If you are aware of an adverse effect of a drug, you will think you have it
e.g. you know a drug could cause muscle aches > you think you have muscle aches even if you don’t

Question 20

What is the mechanism of fibrates?

Answer 20

• Activation of PPARa
• increase production of lipoprotein lipase
• increases triglyceride removal + fatty acid uptake by liver

Question 21

What are adverse effects of fibrates?

Answer 21

GI upset
Myositis
Cholelithiasis

Question 22

What are contraindications of fibrates?

Answer 22

Gall bladder disease
Photosensitivity

Question 23

What is an important drug drug interaction of fibrates?

Answer 23

Warfarin - increase anticoagulation

Question 24

Examples of fibrates

Answer 24

Fenofibrate

Question 25

What is the mechanisms of action of cholesterol absorption inhibitors?

Answer 25

- **Inhibit NPC1L1 transporter at brush border in SI** - reduces absorption of cholesterol by gut - hepatic LDL receptor expression increases - decreases total cholesterol

Question 26

Why is simvastatin given orally?

Answer 26

It is a prodrug Needs to pass through first pass metabolism

Question 27

What are adverse effects of cholesterol absorption inhibitors?

Answer 27

Abdo pain GI upset Angioedma

Question 28

What are contraindications of cholesterol absorption inhibitors?

Answer 28

Hepatic failure

Question 29

What are important drug drug interactions of cholesterol absorption inhibitors?

Answer 29

Ciclosporin Fibrates

Question 30

Example of cholesterol absorption inhibitor

Answer 30

Ezetimibe

Question 31

What is the mechanism of action for bempedoic acid?

Answer 31

**ATP citrate lyase inhibitor** Reduction of cholesterol synthesised

Question 32

Why does bempedoic acid have fewer muscle adverse drug reactions compared to stains?

Answer 32

It is a prodrug metabolised to active form which is almost exclusively in liver

Question 33

What are the adverse effects of bempedoic acid?

Answer 33

Hyperuricaemia - gout Anaemia Pain in extremity

Question 34

What are contradictions of bempedoic acid

Answer 34

Pregnancy Breastfeeding Gout

Question 35

What is the mechanism of action of alirocumab?

Answer 35

- binds to pro-protein > inhibits PCSK9 - this protein is involved in regulation of LDL receptors on liver cells - increases receptor numbers - increased LDL uptake from blood

Question 36

Which statin is offered as a first line option to patients in the UK and why?

Answer 36

Atorvastatin High intensity for low dose + cost

Question 37

What can be added to diet to decrease cholesterol?

Answer 37

Fibre Whole grains Fish oils/oily fish Vitamin C/E

Question 38

What effect does drinking alcohol have on cardiovascular health?

Answer 38

Increases HDL (good) Increases triglycerides (bad)

Question 39

Compare the mechanism of action of alirocumab + inclisiran

Answer 39

- **alirocumab**: block PCSK9 action - **inclisiran**: inhibit hepatic translation of PCSK9 > less produced

Question 40

What is the mechanism of action of inclisiran?

Answer 40

- small interfering RNA - inhibits hepatic translation of PCSK9 - **limits production of PCSK9** - this increases uptake of LDL cholesterol - lower levels in blood

Question 41

What does QRISK tell you?

Answer 41

Chance of having a cardiovascular condition in next 10 years

Question 42

What QRISK would indicate statin administration?

Answer 42

>10%

Question 43

What is given for primary prevention of CVD?

Answer 43

20mg atorvastatin

Question 44

What is given for secondary prevention of CVD?

Answer 44

80mg atorvastatin 20mg atorvastatin if CKD

Question 45

Pharmacological management of Hyperlipidaemia stepwise approach

Answer 45

- **statin**: first line *20mg atorvastatin, then 80mg* - **add *ezetimibe*** - **add *fenofibrate***

Question 46

Target levels for: - total cholesterol - HDL - LDL

Answer 46

- **total cholesterol**: <5 - **HDL**: 1.0+ - **LDL**: <4

Question 47

Conservative management of Hyperlipidaemia

Answer 47

- low fat + high fibre diet (Mediterranean) - no smoking - control HTN - weight loss - reduce alcohol - regular exercise

Question 48

Follow up after starting Hyperlipidaemia management

Answer 48

- lipid profile again 2-3 months after starting statin - aim to lower non HDL cholesterol by 40% - if not met, discuss adherence, taking at correct time, consider changing dose or addition medication - continue to encourage lifestyle changes - assess for adverse affects - annual medications reviews

Question 49

When should statins be stopped before trying to conceive?

Answer 49

3 months

Question 50

In what scenarios can QRISK underestimate CVS risk?

Answer 50

- people treated for HIV - serious mental health problems - meds that can cause dyslipidaemia *e.g. corticosteroids, immunosuppressants, antipyschotics* - autoimmune disorders *e.g. SLE*

Question 51

Primary prevention of cardio vascaulr disease in adults with type 1 diabetes mellitus

Answer 51

Offer 20mg atorvastatin if: - >40 - have diabetes for >10 years - established - other CVD risk factors

Question 52

Primary prevention of cardio vascular disease in CKD

Answer 52

Offer atorvastatin 20mg