Drugs effecting atherosclerosis Flashcards
what is the central core of lipoproteins composed of
HYDROPHOBIC
triglycerides or cholesterol esters
what is the coat of the lipoprotein composed of
hydrophilic coat of polar substances - phopholipids - free cholesterol - associated proteins apoproteins or apolipoproteins
what are the four main variations of lipoproteins
core lipids
apoproteins
size
density
what are the five main classes of lipoproteins
HDL IDL LDL VLDL chylomicrons
what acts as a transport molecules for TG and cholesterol esters
chylomicrons
what are the three outcomes when chylomicrons enter the liver
cholesterol is stored
cholesterol is oxidised to bile acids
released to VLDL which transport cholesterol and newly synthesised triglycerides to tissues
what happens to the TGs on VLDL
they are removed leaving an LDL with a high cholesterol which is taken up by cells pr liver
what is the role of HDL
absorbs cholesterol from cell breakdown and transfer it to VLDL and LDL
what is a risk factor for atheromatous disease
increase in plasma cholesterol associated with increase in LDL
THIS IS CALLED HYPERLIPIDAEMIA
What is stenosis
narrowing
what is an ideal level of cholesterol
less than 5 mmol/l
mildly high cholesterol
5 to 6.4 mmol/l
high cholesterol
6.5 to 7.8 mmol/l
very high cholesterol
above 7.8 mmol/l
how do lipid lowering drugs act and what are the alternatives
either by reducing production of lipoproteins or increasing their removal from the blood as the aim is to reduce plasma cholesterol
- lifestyle modification (diet and excercise)
- drug therapy should be secondary
where is cholesterol derived from
- de nova synthesis in liver
- uptake from circulating LDL’s
- Uptake of chylomicron remnants
PCSK9 (enzyme that mediates degradation of LDL receptors on the surface of liver cells) inhibitors
alirocumab and evolcumab
inhibiting the enzyme increases the amount of LDL bound and cleared by the liver
side effects of stratins
myositis angio-oedema GI disturbances insomnia rash
side effects of fibres
myositis
Gi disturbances
side effects of colestyramine, ezetimibe
GI symptoms
side effects of nicotinic acid
flushing
palpitations
GI disturbances
what are the clinical uses of statins
- primary prevention of arterial disease in patent with high serum cholesterol
- secondary prevention of myocardial infarction and stroke in those who have atherosclerotic diseases
- atorvastatin lowers serum cholesterol in familial hypercholesterolaemia
what makes up the mevalonate pathway
cholesterol synthesis and protein prenylation
what is protein preylation
addition of lipid tails to small GTPase signalling molecules
ensures they are localised correctly
clinical uses of fibrates
mixed dyslipidaemia (raised serum triglyceride as well as cholesterol) in patients with low HDL and high risk of atheromatous disease (type 2 diabetes) combined with other lipid lowering drugs in patients with severe treatment resistant dyslipidaemia
