Cholesterol Lowering Drugs Flashcards
what are the 5 main classes of lipoproteins?
- HDL
- IDL
- LDL
- VLDL
- chylomicrons
what do chylomicrons do?
transport TG and cholesterol esters from GI to tissues
- split by lipoprotein lipase to release free fatty acids (FFAs)
where are chylomicron remnants taken up?
the liver
- cholesterol stored, oxidised to bile acids or released to VLDL
what does VLDL do?
transports cholesterol and newly synthesised TG to tissues
- TGs removed from VLDL leaving LDL with a high cholesterol (taken up by cells or liver)
what is the relationship between plasma cholesterol and LDL?
increased plasma cholesterol associated with increased LDL is a risk factor for atheromatous disease
- may lead to atherosclerosis, ischaemic heart disease, MI and cerebral vascular incidents
what is the term for an increase in plasma concentration of lipids?
hyperlipidaemia
what is the average total cholesterol level in UK?
5.7mmol/l
what is the ideal level of total cholesterol?
<5mmol/l
what is the aim of lipid lowering drugs?
to reduce plasma cholesterol by:
+ reducing production of lipoproteins
OR
+ increasing lipoprotein removal from blood
what 3 sources is cholesterol derived from?
+ de novo synthesis in liver
+ uptake from circulating LDLs
+ uptake of chylomicron remnants
what is the main action of colestyramine?
to sequester bile acids in the intestine/decrease hepatic stores of cholesterol
what is the main action of ezetimibe?
to inhibit the transport protein for cholesterol in the brush border of enterocytes in the duodenum
what is the main action of fibrates?
to alter the levels of plasma lipoproteins
what is the main action of simvastatins, pravastatins, atorvastatins and rosuvastatins?
to inhibit the synthesis of cholesterol in liver
what is colestyramine?
a basic anion exchange resin:
- sequesters bile acids to prevent enterohepatic recirculation
- ∴↑ metabolism of endogenous cholesterol into bile acids
- ↑LDL receptor numbers in liver resulting in removal of LDLs from blood
what combination can lower blood cholesterol by 50%?
bile-sequestering drugs plus inhibitors of cholesterol biosynthesis
what are examples of fibrates?
+ fenofibrates
+ bezafibrates
+ gemfibrozils
how do fibrates work?
+↓plasma triglycerides and, to a lesser extent, cholesterol
+ particularly ↓ elevated concentrations of VLDL
+ main action is stimulation of lipoprotein lipase
which ↓ the triglyceride content of VLDL
+ clearance of LDL by the liver is also stimulated
+ ↑ HDL production and reverse cholesterol transport
what are clinical uses of fibrates?
+ mixed dyslipidaemia (raised serum triglyceride as well as cholesterol)
+ in patients with low HDL and high risk of atheromatous diease (type 2 diabetes)
+ combined with other lipid-lowering drugs for severe treatment resistant dyslipidaemia
what is an example of a nicotinic acid?
niacin
what are nicotinic acids?
vitamin with lipid-lowering properties:
- ↓ VLDL production which leads to ↓ in LDL
- also activates lipoprotein lipase
what does an ezetimibe do?
specifically reduces intestinal cholesterol absorption
- inhibits a sterol carrier protein in brush border of enterocytes
what are statins?
hydroxymethlglutamyl-coenxyme A reductase (HMG-CoA reductase) inhibitors
what does HMG-CoA reductase do?
+ major rate-limiting step in cholesterol synthesis
+ converts HMG-CoA to mevalonic acid (MVA)
what are examples of statins?
simvastatin, pravastatin, atorvastatin, rosuvastatin - long lasting HMG-CoA reductase inhibitors
what are clinical uses of statins?
+ primary prevention of arterial disease in patients with high serum cholesterol
+ secondary prevention of MI and stroke in those who have atherosclerotic diseases
+ atorvastatin lowers serum cholesterol in familial hypercholesterolaemia
what are side effects of statins?
can cause:
- myositis
- angio-oedema
- GI disturbances
- insomnia
- rash
what are side effects of fibrates?
can cause:
- myositis (esp. in patients with renal impairment)
- GI disturbances
what are side effects of colestyramine and ezetimibe?
can cause GI symptoms:
- nausea
- abdominal bloating
- constipation
- diarrhoea
what are side effects of nicotinic acids?
can cause:
- flushing
- palpitations
- GI disturbances
