Hyperlipidaemias Flashcards
What is the mechanism of action of statins?
- 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
What is cholesterol essential for?
- Membrane integrity
- Production of steroid horomones, bile acids + vitamin D
Types of lipoproteins
Chylomicrons
VLDL
IDL
LDL
HDL
Function of Chylomicron
Transports dietary TAGs from intestines to tissue
Function of VLDL
Transport liver synthesised TAGs to adipose tissue for storage
Function of IDLs
Transport liver synthesised cholesterol to tissues
Function of LDLs
Transport liver synthesised cholesterol to tissue
Function of HDLs
Transports excess tissue cholesterol to liver for disposal as bile salts
What are the uses of stains?
Hypercholesterolaemia
Prevention of cardiovascular disease
Reduce risk of atherosclerosis
What are the adverse effects of statins?
- GI disruption > nausea, constipation + diarrhoea
- headache
- diffuse muscle pain
- increased liver enzymes
- Rhabdomyolysis (rare)
What are contraindications of statins?
Renal or hepatic impairment
Pregnancy or breastfeeding
What are the important drug drug interactions of stains?
Amlodipine
Drugs which inhibit CYP3A4: amiodarone, Macrolides (e.g. clarithromycin)
What effects do statins have that contribute towards reduction in cardiovascular disease risk?
- reduce cholesterol
- improved vascular endothelial function
- stabilising of atherosclerotic plaques
- improved haemostasis
- anti-inflammatory + antioxidant
= reduction in cardiovascular disease risk
Examples of statins
Atorvastain
Rosuvastatin
Simvastatin
What is the suffix of stains?
-statin
Why may a simvastatin be suggested to be taken at night time?
- Most cholesterol is made at night
- Simvastatin has a short half life
- Can have the ‘best aciton’
Why shouldn’t you have grapefruit juice whilst taking statins?
Grapefruit inhibit CYP3A4 causes higher levels of stain in blood
Difference between primary and secondary prevention of CVD
- primary prevention: for people at high risk of CVD
- secondary prevention: for people who already have CVD
What is the nocebo effect?
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
What is the mechanism of fibrates?
- Activation of PPARa
- increase production of lipoprotein lipase
- increases triglyceride removal + fatty acid uptake by liver
What are adverse effects of fibrates?
GI upset
Myositis
Cholelithiasis
What are contraindications of fibrates?
Gall bladder disease
Photosensitivity
What is an important drug drug interaction of fibrates?
Warfarin - increase anticoagulation
Examples of fibrates
Fenofibrate
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
Why is simvastatin given orally?
It is a prodrug
Needs to pass through first pass metabolism
What are adverse effects of cholesterol absorption inhibitors?
Abdo pain
GI upset
Angioedma
What are contraindications of cholesterol absorption inhibitors?
Hepatic failure
What are important drug drug interactions of cholesterol absorption inhibitors?
Ciclosporin
Fibrates
Example of cholesterol absorption inhibitor
Ezetimibe
What is the mechanism of action for bempedoic acid?
ATP citrate lyase inhibitor
Reduction of cholesterol synthesised
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
What are the adverse effects of bempedoic acid?
Hyperuricaemia - gout
Anaemia
Pain in extremity
What are contradictions of bempedoic acid
Pregnancy
Breastfeeding
Gout
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
Which statin is offered as a first line option to patients in the UK and why?
Atorvastatin
High intensity for low dose + cost
What can be added to diet to decrease cholesterol?
Fibre
Whole grains
Fish oils/oily fish
Vitamin C/E
What effect does drinking alcohol have on cardiovascular health?
Increases HDL (good)
Increases triglycerides (bad)
Compare the mechanism of action of alirocumab + inclisiran
- alirocumab: block PCSK9 action
- inclisiran: inhibit hepatic translation of PCSK9 > less produced
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
What does QRISK tell you?
Chance of having a cardiovascular condition in next 10 years
What QRISK would indicate statin administration?
> 10%
What is given for primary prevention of CVD?
20mg atorvastatin
What is given for secondary prevention of CVD?
80mg atorvastatin
20mg atorvastatin if CKD
