lipid lowering drugs Flashcards
what is the central core of lipoproteins made up of?
triglycerides (cholesterol esters)
what is the outer hydrophilic coat of lipoproteins made up of?
phospholipids
free cholesterol
unique apoproteins/apolipoproteins
what is the ‘good’ lipoproteins?
HDL
what is the ‘bad’ lipoproteins?
LDL
how is cholesterol taken up from the diet?
cholesterol is produced when fats are broken down along with fatty acids and glycerol. Taken up by CHYLOMICRONS
what is the contents of chylomicrons like?
they have a higher content of triglycerides than esterified cholesterol
how are fatty acids released from chylomicrons?
by the enzyme lipoprotein lipase
what type of tissue takes up free fatty acids?
muscle tissue and adipose tissue
what happens to the CHYLOMICRON REMNANTS (chylomicrons without fatty acids in them)
they are taken up by the liver by ENDOCYTOSIS
what happens to the cholesterol once it reaches the liver?
it can be stored, oxidised to bile acids or releases as VLDL for transportation of fatty acids to other tissues
what does HDL do?
absorbs cholesterol from cell breakdown and transfers it to VLDL and LDL
what diseases are associated with an increase in plasma cholesterol associated with high LDL?
atheromatous disease - may lead to atherosclerosis, ischaemic heart disease, myocardial infarction and cerebral vascular accidents
how is the level of total cholesterol calculated?
total lipoproteins - HDL
what is the IDEAL level of cholesterol?
less tha 5mmol/l
what is a mildly high level of cholesterol?
5 to 6.4mmol/l
what is a moderately high level of cholesterol?
6.5 to 7.8
what is a very high cholesterol level?
more than 7.8
what is the three ways which cholesterol can be derived?
- de novo synthesis in the liver
- uptake from circulating LDLs
- uptake from chylomicron remnants
which drug prevents bile acids from entering hepatic recirculation and therefore increases the metabolism of endogenous cholesterol into bile acids and increase the number of LDL receptor numbers resulting in the removal of LDLs from the blood?
Colestyramine
which class of lipid lowering drug has a main action of stimulating lipoprotein lipase which decreases the triglyceride content of VLDL, increases clearance of LDL by the liver and increases HDL production and reverse cholesterol transport?
fibrates eg fenofibrate, gemfibrozol
what patients are usually given fibres?
patients with low HDL and high risk of atheromatous disease (i.e. type 2 diabetes)
what is the mechanism of action of niacin (nicotinic acid)?
decreases VLDL production which leads to a decrease in LDL, also activates lipoprotein lipase
which drug specifically reduces intestinal cholesterol absorption by inhibiting a sterol carrier in the brush border of enterocytes?
Ezetimibe
what is the major rate limiting step in the production of cholesterol in the liver which STATINS INHIBIT?
step which involves HMG-CoA reductase - converts HMG-CoA to mevalonic acid (MVA)
what are some examples of statins?
simvastatin, pravastatin, atorvastatin and rosuvastatin
what are the two half of the mevalonate pathway?
first half = cholesterol synthesis
second half = protein prenylation
what does the protein prenylation step involve?
addition of lipid tails to seal GTPase molecules and ensures they are localised correctly in the plasma membrane
which patients are given statins as a secondary prevention of myocardial infarction?
those who have atherosclerotic diseases
which patients are given statins as a primary prevention of arterial disease?
patients with high serum cholesterol
which statin lowers serum cholesterol in familial hypercholesterolaemia?
atorvastatin
what is a common side effect of lipid lowering drugs?
GI disturbances
which lipid lowering drugs can cause myositis (inflammation and degeneration of muscle)?
statins and fibrates
