Flashcards in Lipid/Cholesterol Lowering Drugs Deck (41):
What is the arrangement of hydrophobic and hydrophilic lipids in lipoproteins?
Central core of hydrophobic lipid (triglycerides or cholesterol esters)
Hydrophilic coat of polar substances (phospholipids, free cholesterol, associated proteins)
Name the five main classes of lipoproteins.
What do the different classes of lipoproteins vary in?
What is the function of chylomicrons?
Transport triglycerides and cholesterol from the GI to tissues
What is the function of lipoprotein lipase?
Splits chylomicrons to release free fatty acids
Which structures take up free fatty acids?
Muscle and adipose tissue
What happens to the remaining chylomicron remnants following transportation to the tissues and chylomicron lipase breakdown?
Chylomicrons are taken up in the liver
What is the function of VLDLs?
To transport cholesterol and newly synthesised triglycerides to tissues
HDLs absorb cholesterol from cell breakdown. Where do they transfer the cholesterol to?
VLDLs & LDLs
Increased levels of plasma lipids, particularly cholesterol (LDL) is a common feature of what disease?
What can atherosclerosis lead to?
Ischaemic heart disease
Cerebral vascular accidents
What is the name given to an increase in the plasma concentration of lipids?
What is the average TOTAL cholesterol level in the UK?
What is the ideal level of cholesterol one should possess?
What is classed as high and very high cholesterol levels respectively?
Very High: >7.8mmol/l
When looking at average cholesterol levels, what is important to take into account?
Ratio between good (HDL) and bad (LDL) cholesterol
Other risk factors for cardiovascular disease, e.g. smoking, diabetes, high BP, etc.
How do lipid lowering drugs act?
Either reduce the production of lipoproteins or increase their removal from the blood
What should be the first step to lowering cholesterol levels before considering drug therapy?
Which 3 sources is cholesterol derived from?
De Novo synthesis in liver
Uptake from circulating LDLs
Uptake of chylomicron remnants
How does colstyramine act?
Sequesters (isolates) bile acids, preventing enterohepatic recirculation ---> decrease in ABSORPTION of exogenous (external origin) cholesterol ---> increase in METABOLISM of endogenous cholesterol into bile acids ---> increase in numbers of LDL receptors in the live so decrease of LDLs in the blood
How much can bile sequestering drugs such as colestyramine lower blood cholesterol?
What type of 'resin' is colestyramine?
Basic anion exchange resin
Give an example of a lipid lowering drug which inhibits the transport protein for cholesterol in the brush border of enterocytes in the duodenum.
How do fibrates act?
They alter the levels of plasma lipoproteins through activation of lipoprotein lipase (decreases triglyceride content of VLDLs)
Clearence of LDLs by the liver is also stimulated
HDL production is increased
Give some examples of fibrates.
Give some examples of where fibrates are used in clinical context.
In patients with low HDL and high risk of atheromatous disease (e.g. Type 2 diabetes)
In combo with other LLDs in patients with severe treatment resistant dyslipidaemia
Briefly describe the action that nicotinic acid has on lipoproteins.
Decreases VLDL production leading to a decrease in LDLs
Also activates lipoprotein lipase
What are statins?
HMG-CoA reductase inhibitors
What does HMG-CoA reductase do?
It is involved in a major rate limiting step in cholesterol synthesis - converts HMG-CoA to mevalonic acid (MVA)
Give some examples of common statins.
In very basic terms, what do statins do?
Inhibit production of cholesterol
What is a side effect of colestyramine
Can cause GI symptoms such s bloating, nausea, constipation, diahorrea
Any side effects of fibrates?
Can cause myositis (inflammation and degeneration of muscle tissue)
List some side effects of nicotinic acid usage.
Two halves make up the mevalonate pathway - what are they?
What is protein prenylation?
The addition of lipid tails to small GTPase signalling molecules
What is protein prenylation necessary?
It ensures the GTPase molecules are localised correctly
List some clinical uses of statins.
Secondary prevention of MI & stroke in those who have atherosclerotic diseases
Primary prevention of arterial disease in patients with high serum cholesterol
What action does atorvastatin have specifically?
Lowers serum cholesterol in familial hypercholesterolaemia
What is meant by 'serum cholesterol'?
Total cholesterol, i.e. HDL + LDL + IDL, etc.