Hyperlipidaemia Flashcards
describe what HDL particles do
transport excess cholesterol from tissues to liver for elimination
describe what LDL particles do
transport cholesterol from liver to muscle and adipose tissue
describe what VLDLs do
transport newly synthesised TG from liver to muscle and adipose tissue
describe what chylomicrons do
transport lipids from intestines to liver muscle and adipose tissue
when do we start treatment for hyperlipidaemia?
- high CVD risk (>15%)
- moderate risk (10-15%): if lifestyle modification is inadequate after 3-6 months
common examples of statins?
atorvastatin, fluvastatin, pravastatin, rosuvastatin, simvastatin
MoA of statins?
- competitively inhibit HMG-CoA reductase (which is involved in cholesterol synthesis)
- HMG-CoA reductase inhibition –> decreased hepatic cholesterol synthesis –> increased demand for cholesterol –> increased expression of LDL receptors –> increased plasma LDL clearance –> decreased plasma LDL
other potential beneficial actions of statins?
- decrease plasma TG
- increase plasma HDL
- improved endothelial function
- reduced vascular inflammation
- reduced platelet agreeability
- increased neovascularisation of ischaemic tissue
- stabilisation of atherosclerotic plaque
- antithrombotic actions
enhanced fibrinolysis
pharmacokinetics of statins?
- metabolism: liver CYP450 enzymes (except pravastatin which is renally cleared)
- excretion: biliary
which statins have short half-lives
fluvastatin, pravastatin, simvastatin (1.5-4h)
which statin have long half-lives
atorvastatin, rosuvastatin (20-30h)
adverse effects of statins?
- common: myalgia, mild GI disturbances, elevated aminotransferase concentrations
- rarely: rhabdomyolysis
clinical use of statins?
- hypercholesterolaemia
- high risk of coronary heart disease, with or without hypercholesterolaemia
MoA of ezetimibe?
decreases absorption of exogenous cholesterol by blocking transport protein NPC1L1 in small intestine enterocytes –> increased cholesterol demand –> increased LDL receptors expression –> increased plasma LDL clearance –> decreased plasma LDL concentration
adverse effects of ezetimibe?
- generally very well tolerated
- headache, abdominal pain, diarrhoea
clinical use of ezetimibe?
hypercholesterolaemia (when statins are not well tolerated or can be added to statins)
what does bile acids facilitate?
- lipids absorption and regulate cholesterol homeostasis
- primary pathway for cholesterol catabolism
where are bile acids synthesised?
synthesised in liver via cholesterol oxidation
what mechanism is bile acids recycled through?
enterohepatic recirculation, where about 95% of bile acids are delivered to duodenum and reabsorbed within ileum
common example of bile-acid binding resins?
cholestyramine
MoA of bile acid binding resins?
bind bile acids in intestinal lumen, preventing reabsorption and increase bile acid excretion in faeces —> decreased absorption of exogenous cholesterol and increased metabolism of endogenous cholesterol into bile acids –> increased demand for cholesterol –> increased LDL receptors expression –> increased plasma LDL clearance –> reduced plasma LDL concentration
what are some problems with therapy with bile acid binding resins?
- increase plasma TG (avoid use if plasma TG >3mmol/L)
- decreased absorption of fat-soluble vitamins (ADEK)
- decreased absorption of some orally administered drugs (take other medications 1 hour before or 4 hours after the resin)
- low patient adherence levels due to its unpleasant texture
adverse effects of bile acid binding resins?
- GI disturbances - constipation, abdominal pain, flatulence, dyspepsia, nausea, vomiting, diarrhoea. anorexia, increase TG
clinical use of bile acid binding resins?
combination treatment when stain alone is inadequate
