Hyperlipidaemias Flashcards

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1
Q

What is the mechanism of action of statins?

A
  • 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
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2
Q

What is cholesterol essential for?

A
  • Membrane integrity
  • Production of steroid horomones, bile acids + vitamin D
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3
Q

Types of lipoproteins

A

Chylomicrons
VLDL
IDL
LDL
HDL

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4
Q

Function of Chylomicron

A

Transports dietary TAGs from intestines to tissue

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5
Q

Function of VLDL

A

Transport liver synthesised TAGs to adipose tissue for storage

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6
Q

Function of IDLs

A

Transport liver synthesised cholesterol to tissues

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7
Q

Function of LDLs

A

Transport liver synthesised cholesterol to tissue

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8
Q

Function of HDLs

A

Transports excess tissue cholesterol to liver for disposal as bile salts

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9
Q

What are the uses of stains?

A

Hypercholesterolaemia
Prevention of cardiovascular disease
Reduce risk of atherosclerosis

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10
Q

What are the adverse effects of statins?

A
  • GI disruption > nausea, constipation + diarrhoea
  • headache
  • diffuse muscle pain
  • increased liver enzymes
  • Rhabdomyolysis (rare)
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11
Q

What are contraindications of statins?

A

Renal or hepatic impairment
Pregnancy or breastfeeding

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12
Q

What are the important drug drug interactions of stains?

A

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

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13
Q

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

A
  • reduce cholesterol
  • improved vascular endothelial function
  • stabilising of atherosclerotic plaques
  • improved haemostasis
  • anti-inflammatory + antioxidant
    = reduction in cardiovascular disease risk
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14
Q

Examples of statins

A

Atorvastain
Rosuvastatin
Simvastatin

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15
Q

What is the suffix of stains?

A

-statin

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16
Q

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

A
  • Most cholesterol is made at night
  • Simvastatin has a short half life
  • Can have the ‘best aciton’
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17
Q

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

A

Grapefruit inhibit CYP3A4 causes higher levels of stain in blood

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18
Q

Difference between primary and secondary prevention of CVD

A
  • primary prevention: for people at high risk of CVD
  • secondary prevention: for people who already have CVD
19
Q

What is the nocebo effect?

A

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

20
Q

What is the mechanism of fibrates?

A
  • Activation of PPARa
  • increase production of lipoprotein lipase
  • increases triglyceride removal + fatty acid uptake by liver
21
Q

What are adverse effects of fibrates?

A

GI upset
Myositis
Cholelithiasis

22
Q

What are contraindications of fibrates?

A

Gall bladder disease
Photosensitivity

23
Q

What is an important drug drug interaction of fibrates?

A

Warfarin - increase anticoagulation

24
Q

Examples of fibrates

A

Fenofibrate

25
Q

What is the mechanisms of action of cholesterol absorption inhibitors?

A
  • Inhibit NPC1L1 transporter at brush border in SI
  • reduces absorption of cholesterol by gut
  • hepatic LDL receptor expression increases
  • decreases total cholesterol
26
Q

Why is simvastatin given orally?

A

It is a prodrug
Needs to pass through first pass metabolism

27
Q

What are adverse effects of cholesterol absorption inhibitors?

A

Abdo pain
GI upset
Angioedma

28
Q

What are contraindications of cholesterol absorption inhibitors?

A

Hepatic failure

29
Q

What are important drug drug interactions of cholesterol absorption inhibitors?

A

Ciclosporin
Fibrates

30
Q

Example of cholesterol absorption inhibitor

A

Ezetimibe

31
Q

What is the mechanism of action for bempedoic acid?

A

ATP citrate lyase inhibitor
Reduction of cholesterol synthesised

32
Q

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

A

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

33
Q

What are the adverse effects of bempedoic acid?

A

Hyperuricaemia - gout
Anaemia
Pain in extremity

34
Q

What are contradictions of bempedoic acid

A

Pregnancy
Breastfeeding
Gout

35
Q

What is the mechanism of action of alirocumab?

A
  • 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
36
Q

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

A

Atorvastatin

High intensity for low dose + cost

37
Q

What can be added to diet to decrease cholesterol?

A

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

38
Q

What effect does drinking alcohol have on cardiovascular health?

A

Increases HDL (good)
Increases triglycerides (bad)

39
Q

Compare the mechanism of action of alirocumab + inclisiran

A
  • alirocumab: block PCSK9 action
  • inclisiran: inhibit hepatic translation of PCSK9 > less produced
40
Q

What is the mechanism of action of inclisiran?

A
  • small interfering RNA
  • inhibits hepatic translation of PCSK9
  • limits production of PCSK9
  • this increases uptake of LDL cholesterol
  • lower levels in blood
41
Q

What does QRISK tell you?

A

Chance of having a cardiovascular condition in next 10 years

42
Q

What QRISK would indicate statin administration?

A

> 10%

43
Q

What is given for primary prevention of CVD?

A

20mg atorvastatin

44
Q

What is given for secondary prevention of CVD?

A

80mg atorvastatin
20mg atorvastatin if CKD