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MD2002 > Lipid/Cholesterol Lowering Drugs > Flashcards

Lipid/Cholesterol Lowering Drugs Flashcards

1
Q

What is the arrangement of hydrophobic and hydrophilic lipids in lipoproteins?

A

Central core of hydrophobic lipid (triglycerides or cholesterol esters)
Hydrophilic coat of polar substances (phospholipids, free cholesterol, associated proteins)

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2
Q

Name the five main classes of lipoproteins.

A 
HDLs
IDLs
LDLs
VLDLs
Chylomicrons
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3
Q

What do the different classes of lipoproteins vary in?

A

Core lipids
Size
Apoproteins
Density

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4
Q

What is the function of chylomicrons?

A

Transport triglycerides and cholesterol from the GI to tissues

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5
Q

What is the function of lipoprotein lipase?

A

Splits chylomicrons to release free fatty acids

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6
Q

Which structures take up free fatty acids?

A

Muscle and adipose tissue

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7
Q

What happens to the remaining chylomicron remnants following transportation to the tissues and chylomicron lipase breakdown?

A

Chylomicrons are taken up in the liver

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8
Q

What is the function of VLDLs?

A

To transport cholesterol and newly synthesised triglycerides to tissues

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9
Q

HDLs absorb cholesterol from cell breakdown. Where do they transfer the cholesterol to?

A

VLDLs & LDLs

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10
Q

Increased levels of plasma lipids, particularly cholesterol (LDL) is a common feature of what disease?

A

Atherosclerosis

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11
Q

What can atherosclerosis lead to?

A

Ischaemic heart disease
Myocardial infarction
Cerebral vascular accidents

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12
Q

What is the name given to an increase in the plasma concentration of lipids?

A

Hyperlipidaemia

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13
Q

What is the average TOTAL cholesterol level in the UK?

A

5.7mmol/l

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14
Q

What is the ideal level of cholesterol one should possess?

A
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15
Q

What is classed as high and very high cholesterol levels respectively?

A

High: >5mmol/l

Very High: >7.8mmol/l

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16
Q

When looking at average cholesterol levels, what is important to take into account?

A

Ratio between good (HDL) and bad (LDL) cholesterol

Other risk factors for cardiovascular disease, e.g. smoking, diabetes, high BP, etc.

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17
Q

How do lipid lowering drugs act?

A

Either reduce the production of lipoproteins or increase their removal from the blood

18
Q

What should be the first step to lowering cholesterol levels before considering drug therapy?

A

Lifestyle modification

19
Q

Which 3 sources is cholesterol derived from?

A

De Novo synthesis in liver
Uptake from circulating LDLs
Uptake of chylomicron remnants

20
Q

How does colstyramine act?

A

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

21
Q

How much can bile sequestering drugs such as colestyramine lower blood cholesterol?

A

By 50%

22
Q

What type of ‘resin’ is colestyramine?

A

Basic anion exchange resin

23
Q

Give an example of a lipid lowering drug which inhibits the transport protein for cholesterol in the brush border of enterocytes in the duodenum.

A

Ezetimibe

24
Q

How do fibrates act?

A

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

25
Q

Give some examples of fibrates.

A

Fenofibrate
Bezafibrate
Gemfibrozil
Nicotinic acid

26
Q

Give some examples of where fibrates are used in clinical context.

A

Mixed dyslipidaemia
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

27
Q

Briefly describe the action that nicotinic acid has on lipoproteins.

A

Decreases VLDL production leading to a decrease in LDLs

Also activates lipoprotein lipase

28
Q

What are statins?

A

HMG-CoA reductase inhibitors

29
Q

What does HMG-CoA reductase do?

A

It is involved in a major rate limiting step in cholesterol synthesis - converts HMG-CoA to mevalonic acid (MVA)

30
Q

Give some examples of common statins.

A

Simvastatin
Pravastatin
Atorvastatin
Rosuvastatin

31
Q

In very basic terms, what do statins do?

A

Inhibit production of cholesterol

32
Q

What is a side effect of colestyramine

A

Can cause GI symptoms such s bloating, nausea, constipation, diahorrea

33
Q

Any side effects of fibrates?

A

Can cause myositis (inflammation and degeneration of muscle tissue)
GI disturbances

34
Q

List some side effects of nicotinic acid usage.

A

Flushing
Palpitations
GI disturbances

35
Q

Two halves make up the mevalonate pathway - what are they?

A

Cholesterol synthesis

Protein prenylation

36
Q

What is protein prenylation?

A

The addition of lipid tails to small GTPase signalling molecules

37
Q

What is protein prenylation necessary?

A

It ensures the GTPase molecules are localised correctly

38
Q

List some clinical uses of statins.

A

Secondary prevention of MI & stroke in those who have atherosclerotic diseases
Primary prevention of arterial disease in patients with high serum cholesterol

39
Q

What action does atorvastatin have specifically?

A

Lowers serum cholesterol in familial hypercholesterolaemia

40
Q

What is meant by ‘serum cholesterol’?

A

Total cholesterol, i.e. HDL + LDL + IDL, etc.

41
Q

List some side effects of statins.

A 
Myositis
Angio-oedema
GI disturbances
Insomnia (inability to sleep)
Rash

MD2002 (27 decks)

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