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Hyperlipidaemias Flashcards

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
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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

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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
What is the mechanisms of action of cholesterol absorption inhibitors?
- **Inhibit NPC1L1 transporter at brush border in SI** - reduces absorption of cholesterol by gut - hepatic LDL receptor expression increases - decreases total cholesterol
26
Why is simvastatin given orally?
It is a prodrug Needs to pass through first pass metabolism
27
What are adverse effects of cholesterol absorption inhibitors?
Abdo pain GI upset Angioedma
28
What are contraindications of cholesterol absorption inhibitors?
Hepatic failure
29
What are important drug drug interactions of cholesterol absorption inhibitors?
Ciclosporin Fibrates
30
Example of cholesterol absorption inhibitor
Ezetimibe
31
What is the mechanism of action for bempedoic acid?
**ATP citrate lyase inhibitor** Reduction of cholesterol synthesised
32
Why does bempedoic acid have fewer muscle adverse drug reactions compared to stains?
It is a prodrug metabolised to active form which is almost exclusively in liver
33
What are the adverse effects of bempedoic acid?
Hyperuricaemia - gout Anaemia Pain in extremity
34
What are contradictions of bempedoic acid
Pregnancy Breastfeeding Gout
35
What is the mechanism of action of alirocumab?
- 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
Which statin is offered as a first line option to patients in the UK and why?
Atorvastatin High intensity for low dose + cost
37
What can be added to diet to decrease cholesterol?
Fibre Whole grains Fish oils/oily fish Vitamin C/E
38
What effect does drinking alcohol have on cardiovascular health?
Increases HDL (good) Increases triglycerides (bad)
39
Compare the mechanism of action of alirocumab + inclisiran
- **alirocumab**: block PCSK9 action - **inclisiran**: inhibit hepatic translation of PCSK9 > less produced
40
What is the mechanism of action of inclisiran?
- small interfering RNA - inhibits hepatic translation of PCSK9 - **limits production of PCSK9** - this increases uptake of LDL cholesterol - lower levels in blood
41
What does QRISK tell you?
Chance of having a cardiovascular condition in next 10 years
42
What QRISK would indicate statin administration?
>10%
43
What is given for primary prevention of CVD?
20mg atorvastatin
44
What is given for secondary prevention of CVD?
80mg atorvastatin 20mg atorvastatin if CKD
45
Pharmacological management of Hyperlipidaemia stepwise approach
- **statin**: first line *20mg atorvastatin, then 80mg - **add *ezetimibe*** - **add *fenofibrate***
46
Target levels for: - total cholesterol - HDL - LDL
- **total cholesterol**: <5 - **HDL**: 1.0+ - **LDL**: <4
47
Conservative management of Hyperlipidaemia
- low fat + high fibre diet (Mediterranean) - no smoking - control HTN - weight loss - reduce alcohol - regular exercise
48
Follow up after starting Hyperlipidaemia management
- lipid profile again 2-3 months after starting statin - aim to lower non HDL cholesterol by 40% - if not met, discuss adherence, correct time, consider changing dose or addition medication - assess for adverse affects

CPT (29 decks)

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