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YR2 LCRS Pharm > Atherosclerosis, Lipoproteins and Lipid-Lowering Agents > Flashcards

Atherosclerosis, Lipoproteins and Lipid-Lowering Agents Flashcards

1
Q

What is the main difference in the composition of LDLs and HDLs?

A

They have different apoproteins

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2
Q

What are dietary triglycerides and cholesterol packaged into once they are absorbed?

A

Chylomicrons

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3
Q

What are chylomicrons broken down into? What breaks them down?

A

Chylomicron remnants

By Lipoprotein lipase

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4
Q

Are most circulating lipids endogenous or exogenous?

A

Endogenous

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5
Q

What is the significance of chylomicron remnants with regards to atherosclerosis?

A

They are very good at getting into the tunica intima

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6
Q

Define atherosclerosis.

A

An inflammatory fibro-proliferative disorder

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7
Q

What cells are recruited in the process of atherosclerosis?

A

Macrophages (which turn into foam cells)
Fibroblasts
Smooth muscle cells

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8
Q

What must initially happen for the process of atherosclerosis to begin?

A

Increase in permeability of the endothelium
Up-regulation of endothelial adhesion molecules (key in inflammation)
Leukocyte adhesion
Migration of leukocytes into arterial wall

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9
Q

What can happen as the atheroma grows larger?

A

Some of the foam cells die + rupture, releasing their toxic contents to form a lipid necrotic core

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10
Q

Which cells are responsible for producing a protective fibrous cap over the fat core? What is the significance of this?

A

Smooth muscle cells lay down collagen fibres.

It separates the thrombogenic lipid rich core from circulating platelets + other coagulation factors

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11
Q

What happens to unstable atherosclerotic plaques?

A

Fibrous cap thins + eventually ruptures, exposing thrombogenic lipid core to platelets + coagulation factors
This causes THROMBOSIS

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12
Q

What are some characteristics of vulnerable plaques?

A

Thin fibrous cap
A core rich in lipid + macrophages
Less evidence of smooth muscle proliferation

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13
Q

What can modify LDL cholesterol?

A

Low HDL
Diabetes
Smoking
Hypertension

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14
Q

What do low HDL cholesterol levels tend to be associated with?

A

Higher risk of atherosclerosis + CHD

High triglyceride levels

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15
Q

What 3 factors can lower HDL cholesterol levels?

A

Smoking
Obesity
Physical inactivity

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16
Q

Other than heart disease, what else is a very high triglyceride level associated with?

A

Pancreatitis

17
Q

State 4 different drug therapies that have been used to treat high cholesterol.

A

Bile acid sequestrants
Nicotinic acid
Fibrates
Statins

18
Q

Describe the mechanism of action of statins.

A

HMG-CoA reductase inhibitors (enzyme involved in the RDS in formation of cholesterol)

19
Q

What are 2 important products of the cholesterol synthesis pathway?

A

Geranyl pyrophosphate
Farnesyl pyrophosphate
Involved in modification + activation of proteins

20
Q

How do statins decrease plasma LDL levels?

A

Statins block the cholesterol synthesis pathway, which leads to the liver responding by producing more LDL receptors
This increases binding + removal of LDL from the blood

21
Q

What is the selectivity ratio of a statin?

A

The higher the selectivity ratio, the greater the likelihood of the molecule being concentrated in the liver cell

22
Q

What is the Rule of 6?

A

Doubling the dose of any statin will give a 6% reduction in the level of LDL

23
Q

How do fibrates act? Which patient group are they often used in?

A

Activate PPAR-alpha
Lead to decreased plasma fatty acids + triglycerides
Often used in diabetics with high triglycerides

24
Q

Name an important drug that can be given with statins to further decrease LDL levels?

A

Ezetimibe – it inhibits cholesterol absorption

25
Q

What is Ezetimibe activated as?

A

Glucuronide

26
Q

Which protein is involved in the transport of cholesteryl esters and triglycerides from HDLs to LDLs?

A

Cholesteryl Ester Transfer Protein (CETP)

27
Q

What was the result of attempted inhibition of CETP?

A

Increased HDL + decreased LDL but it had off target effects that led to increased mortality

28
Q

What is PCSK9?

A

An inhibitor of LDL receptors
Stops LDL in plasma from binding to the LDL receptor + being taken up
PCSK9 inhibition can lead to a decrease in cholesterol levels

29
Q

What characterises a stable atherosclerotic plaque?

A

A necrotic core covered by a thick vascular smooth muscle rich fibrous cap

30
Q

What can promote rupture of an atherosclerotic plaque?

A

High BP

Inflammation

31
Q

Which diseases are strongly associated with high levels of LDL cholesterol?

A

Atherosclerosis

CHD Events

32
Q

Expression of what is induced by statins? How does this have a counterintuitive effect?

A

LDLR + PCSK9
Increase in LDLR to bind LDL
But increase in PCSK9 inhibits LDLR

YR2 LCRS Pharm (34 decks)

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