Hyperlipidaemia Flashcards
Where and how is cholesterol synthesised?
Synthesised in the liver via the mevalonate pathway.
What is the rate limiting enzyme in the cholesterol synthesis pathway?
HMG-CoA reductase - RLE in mevalonate pathway.
What is the paradox effect of cholesterol on the cell membrane?
At high temperatures, it restrains movement and prevents membrane from melting.
At low temperatures, it prevents stiffness and prevents membrane from freezing.
What is familial hyperlipidaemia? Name 3 physical signs.
Early development of atherosclerosis due to genetic variant in apolipoproteins.
Corneal arcus, xanthelasma, xanthoma.
Name 2 statins.
Atorvastatin
Simvastatin
What is the MOA of statins?
Competitively inhibits HMG-CoA reductase, the RLE in the mevalonate pathway that produces cholesterol.
Also increases expression of hepatic LDL receptors - increases LDL clearance.
What time of day should statins be taken?
Just before bed, since LDL receptor synthesis is highest at this time - increases clearance of LDL and increases effectiveness.
What needs to happen to simvastatin for it to become active?
Undergoes first pass metabolism to produce active metabolites (it’s a prodrug).
Name some side effects/ADRs of statins.
- myalgia
- rhabdomyolysis
- GI disruption
- nausea
- headache
- elevated serum transaminase - due to liver injury
Name some ways in which statins reduce risk of CVD.
- stabilisation of atherosclerotic plaques
- anti-inflammatory
- antioxidant
Name a fibric acid derivative used as a lipid lowering drug.
Fenofibrate
What is the MOA of fibric acid derivatives?
Activates the transcription factor PPAR-alpha, which regulates expression of lipoprotein lipase gene (RLE for hydrolysis of triglycerides) - decreases triglyceride.
Increases LDL affinity for its receptor - decreases LDL.
Name some contraindications for lipid lowering drugs.
Hepatic or renal dysfunction (as most of them cause hepatotoxicity).
Name some side effects of fibric acid derivatives.
- GI upset
- gall stones
- myosotis (inflammation of muscles)
- abnormal LFTs
What drug does fibric acid derivatives interact with?
Warfarin - causes warfarin potentiation (increases effects of warfarin).
Name a nicotinic acid drug that is used for lipid lowering.
Niacin
What is the MOA of niacin?
Reduces fatty acid supply and therefore triglyceride synthesis.
Name a cholesterol absorption inhibitor.
Ezetimibe
What is the MOA of cholesterol absorption inhibitors?
Act at brush border of small intestine mucosa to inhibit NCPC1L1 transporter and decrease cholesterol absorption.
Increases hepatic LDL receptor expression.
Name some side effects of nicotinic acid.
- flushing, itching
- headache
- GI disturbance
- hepatotoxicity
What type of drug is ezetimibe?
Prodrug.
Name some side effects of cholesterol absorption inhibitors.
- headache
- abdo pain, diarrhoea
Which of the lipid lowering drugs is a useful combination with a stain for patients who can only tolerate a low dose statin?
Ezetimibe - cholesterol absorption inhibitor.
Which drugs are commonly used for familial hypercholesterolaemia?
Fibric acid derivatives
Nicotinic acid
What is the MOA of monoclonal antibodies when used as lipid lowering drugs?
PCSK9 inhibitors - inhibit degradation of LDL receptor - increases LDL clearance.
Name 2 monoclonal antibodies used as lipid lowering drugs.
Alirocumab
Evolocumab
Name some non-prescription options for high cholesterol.
Fish oils
Fibre
Vitamins C and E
Alcohol in small amounts - increases HDL cholesterol
