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PHAR20300 > Lipid lowering drugs > Flashcards

Lipid lowering drugs Flashcards

1
Q

Which organ synthesises lipids?

A

Liver

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2
Q

Are lipids hydrophobic or hydrophilic?

A

Hydrophobic

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3
Q

Cholesterol synthesised in the liver is reffered to as exogenous. True or false?

A

False - endogenous

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4
Q

Cholesterol from diet is referred to as exogenous. True or false?

A

True

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5
Q

Where is triglyceride synthesised?

A

Obtained from the diet or synthesised in the liver

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6
Q

What is the role of lipoproteins and what are they made from?

A

To transport lipids in plasma, solubilise them

They are made of lipids (TGs, cholesterol, phospholipids) and a protein called apolipoprotein

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7
Q

What is the role of apolipoprotein in lipoproteins?

A

It interacts with receptors on target cells

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8
Q

Where is the lipoprotein chylomicron made and what is its job?

A

In the gut (enterocytes)

It transports fats and cholesterol absorbed from the intestine

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9
Q

Which apolipoprotein do chylomicrons contain?

A

ApoB-48

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10
Q

Which apolipoprotein do VLDLs contain?

A

ApoB-100

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11
Q

What is the role of VLDLs and where are they made?

A

They are made in the liver

Transport TGs and cholesterol from the liver to tissue

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12
Q

When VLDLs transport TG and cholesterol to tissues, they lose TG to produce what?

A

IDL and LDL

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13
Q

IDLs are present at high concentrations. True or false?

A

False - low

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14
Q

Which apolipoprotein do LDLs have?

A

ApoB-100

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15
Q

Do LDLs have a high or low TG content?

A

Low

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16
Q

What is the role of LDLs?

A

Deliver cholesterol to tissues

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17
Q

Which apolipoproteins do HDLs have?

A

Apo-A1 and Apo-B2

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18
Q

HDLs have high TG content. True or false?

A

False - little/no TG

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19
Q

What is the role of HDLs?

A

Scavange cholesterol from tissues

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20
Q

What is dyslipidaemia?

A

When something is wrong with lipid levels in the blood

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21
Q

What is meant by hyperlipidaemia?

A

Excessive levels of plasma lipoproteins

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22
Q

What happens in type I hyperlipidaemia and what is the effect?

A

Chylomicrons elevated - no increased risk of atherosclerosis

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23
Q

What happens in type IIa hyperlipidaemia and what are the effects?

A

LDL elevated - high risk of atherosclerosis

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24
Q

What happens in type IIb hyperlipidaemia and what are the effects?

A

LDL elevated and VLDL elevated - high risk of atherosclerosis

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25
Q

Which type of hyperlipidaemia is a result of IDL levels being elevated and what effect does this have on risk of atherosclerosis?

A

Type III and there is moderate risk of atherosclerosis

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26
Q

What is type IV hyperlipidaemia?

A

VLDL elevated - moderate risk of atherosclerosis

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27
Q

What is type V hyperlipidaemia?

A

VLDL and chylomicrons elevated - no increased risk of atherosclerosis

28
Q

Which enzyme breaks down TG in lipoproteins?

A

Lipoprotein lipase

29
Q

Lipoprotein lipase removes TG from LDLs. True or false?

A

False - removes from VLDL and chylomicrons where levels of TG are high

30
Q

What is left of the chylomicron when TG is removed by lipoprotein lipase?

A

TG remenant and cholesterol - cholesterol is removed in circulation by the liver

31
Q

What is left of VLDL when TG is removed by lipoprotein lipase?

A

LDL - this is removed by LDL receptors by endocytosis (which are found in all cells but abundant in liver)

32
Q

LDL receptors are synthesised within cells. True or false?

A

True

33
Q

Surface expression of LDL receptors is increased when intracellular cholesterol is high. True or false?

A

False - reduced expression

34
Q

What does an increase in number of LDL receptors do to serum LDL levels?

A

Reduce them

35
Q

What are clathrin coated pits?

A

LDL receptors that have bound to LDL on the surface are internalised by clathrin coated pits and the LDL is then segregated and broken down, and the receptor is recycled back to plasma membrane

36
Q

Most of the cholesterol absorbed from the intestine ends up in the liver. True or false?

A

True

37
Q

Where is cholesterol taken up in the diet digested?

A

In the intestine

38
Q

What are bile acids made from?

A

Cholesterol

39
Q

Where are bile acids made?

A

In the liver and then are transported to the intestine via bile duct as they are needed for the absorption of cholesterol from the intestine to liver

40
Q

What is the role of bile acids?

A

Esterify dietary fats and make them more miscible with water, allowing cholesterol etc. to be taken up by cells

41
Q

After bile acids esterify fats, what happens?

A

Cholesterol etc. can be taken up by cells and some cholesterol and bile acid return to liver via hepatic portal vein to be recycled

42
Q

LDL inhibits fibrinolysis and platelet aggregation. True or false?

A

False - inhibits fibrinolysis but promotes platelet aggregation and so promotes thrombosis

43
Q

How many mmol/L should total cholesterol be in healthy adults?

A

5mmol/L or less

44
Q

How many mmol/L should LDL be in healthy adults?

A

3mmol/L

45
Q

HDL should be 1mmol/L or more. True or false?

A

True

46
Q

What should the ratio of total cholesterol: HDL be?

A

< 4

47
Q

What is the function of PCSK9?

A

It binds to the LDL receptor before endocytosed and is internalised with it.
It interferes with the recycling of the LDL receptor and targets it for degradation. This means less LDL receptors can be recycled to plasma membrane so less LDL can be broken down

48
Q

People with loss of function of PCSK9 are at lower risk of cardiovascular risk. Why?

A

Because they have lower LDL levels

49
Q

Hypercholesterolaemia can be inherited. True or false?

A

True

50
Q

What is the main aim of treatment for hyperlipidaemia?

A

Reduce total cholesterol, reduce LDL and increase HDL

51
Q

What are the class of drugs that are first line for treatment of high LDL levels?

A

Statins

52
Q

Which enzyme do statins competitively inhibit?

A

HMG-CoA reductase

53
Q

What side effects do statins cause?

A

Myositis (muscle inflammation)

Rhabdomyolysis - muscle breakdown

54
Q

Statins block endogenous liver synthesis in the liver. True or false?

A

True

55
Q

Grapefruit juice interacts with which class of lipid-lowering drugs?

A

Statins

56
Q

How does Ezetimibe work?

A

Blocks NPC1L1 cholesterol transporter and so less dietary cholesterol is absorbed so instead of being taken up by liver it remains in gut where it eventually passes out as faeces

57
Q

Ezitimibe is an adjunct to statins. Why?

A

So there is inhibition of synthesis of cholesterol by liver and the uptake of it - increased effect

58
Q

What side effects may ezitimibe cause?

A

Myopathy, GI disturbances

59
Q

How do bile acid sequestrants affect absorption of cholesterol from the diet?

A

Because bile acids are needed for emulsification of dietary cholesterol

60
Q

Bile acid sequestrants interfere with absorption of fat soluble vitamins so supplements may be needed. What are the fat soluble vitamins?

A

Vitamins A, D, K

61
Q

What is the mechanism of action of Evolocumab and Alirocumab?

A

They are antibodies for PCSK9 and so prevent it from degrading LDL receptors so these can be expressed on plasma membrane and continue to breakdown LDL

62
Q

Why should fibrates not be used with statins?

A

Increased risk of rhabdomyolysis

63
Q

How does nicotinic acid and its derivatives work?

A

Reduce VLDL and upregulate HDL

64
Q

What is the main unwanted effect of nicotinic acid?

A

Facial flushing

65
Q

How do fibrates work?

A

Reduce VLDL and upregulate HDL

66
Q

Fibrates are only used with patients with elevated TG. True or false?

A

True

67
Q

Fibrates are PPARa antagonists. True or false?

A

False - agonists

PHAR20300 (25 decks)

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