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Drugs > L15- Drugs affecting plasma lipids > Flashcards

L15- Drugs affecting plasma lipids Flashcards

1
Q

What are lipoproteins composed of?

A

Lipids (triglyceride or cholesterol esters)

PLUS

Phospholipids, cholesterol, proteins

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2
Q

WHat are the 5 types of lipoproteins?

A
  1. HDL
  2. LDL
  3. IDL
  4. VLDL
  5. Chylomicrons
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3
Q

Dietary cholesterol and fats are taken up into the blood stream in what form?

A

Chylomicrons

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4
Q

IN the peripheral tissues what happens to the fats from the bloodstream?

A

The fats (chylomicron form) are broken down into fatty acids (which are taken up by the tissues) and glycerol.

Broken down by lipoprotein lipase

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5
Q

What happens to the chylomicron remnants in the blood?

A

The chylomicron remnants are then taken up by the liver and the cholesterol they contain is added to the livers;s synthesized cholesterol.

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6
Q

In what form does the liver secrete cholesterol and newly synthesized triglycerides?

A

VLDL

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7
Q

After the liver has secreted cholesterol and triglycerides what is it converted to?

A

SEcreted as VLDL. Then converted to LDL by the absorption of fatty acids in the peripheral tissue. (again by lipoprotein lipase)

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8
Q

What can the peripheral tissue take up from the LDLs?

A

cholesterol

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9
Q

After the LDLs leave the peripheral tissues, what happens?

A

LDLs can be taken up into the liver via a receptor mediated process

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10
Q

How do HDLs arise?

A

From te recycling of cholesterol (from cell breakdown) in the perippheral tissues.

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11
Q

How are bile acids formed?

A

By the oxidation of cholesterol. They’re then secreted into the GI tract (mixed with cholesterol) and act as detergents + emulsify fats.

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12
Q

What happens to most of the secrted bile?

A

It’s returned to the liver via the portal vein.

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13
Q

What is bad cholesterol?

A

LDL and to a lesser extent VLDL

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14
Q

WHy is bad cholesterol bad?

A

LDL and VLDL are involved in the formation of fatty deposits (fatty streaks) in blood vessels. leads to atherosclerosis

Inhibit fibrin breakdown

Activate platelets- increase aggregation

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15
Q

What are LDL and VLDL a major risk factor for?

A

Thrombosis (increase atherosclerosis- cause thrombosis)

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16
Q

How does HDL help?

A

Lowers the risk of atherosclerosis by:

INcreasing fibrinolysis

Increasing prostacyclin formation- decreasing aggregation

17
Q

What is hyperlipidaemia?

A

HIgh levels of lipis/lipoproteins. Range of forms because of different lipoprotein types

18
Q

What;s the aim of lipid lowering drugs?

A

Reduce LDL and Increase HDL

19
Q

Give 5 examples of drugs used to treat hyperlipidaemias?

A
  1. Statins
  2. Ezetimibe
  3. Fibrates
  4. Exchange resins
  5. nicotinic acid
20
Q

How do statins work?

A

They inhibit HMG-CoA reductase, the rate limiting enzyme in the production of cholesterol.

So rduce cholesterol production.

More LDL receptors on hepatocytes, removing more LDL from plasma.

Also causes an increase in HDL and a decrease in the amount of triglycerides.

21
Q

What do statins do in an arrowed step form?

A

STATIN INHIBITS—- HMG-CoA

Acetyl coenzyme A

mevalonate

Cholesterol

22
Q

What are the side effects of statins?

A
  • muscle inflammation
  • sometimes leads to muscle breaksown which releases toxic substances into the blood. kidney particularly sensitive to this- results in renal failure
23
Q

How does ezetimibe work?

A

It inhibits a specific cholesterol transporter in enterocytes and reduces cholesterol absorption. Leads to lower cholesterol and reduced LDL.

24
Q

How do ion exchange resins like colestyramine work?

A

Also affect absorption of cholesterol from the gut. They do this by binding to the bile acids and stopping them from being reabsorbed. Lower cholesterol absorption and bile acid reacsorption leads to increased conversion of new cholesterol into bile acids and incrased uptake of LDL by liver from blood.

25
Q

Problems with colestyramine?

A

Ion exchange resins cause:

GIT upsets- nausea, diarrhoea etc.

Decreases absorption of fat soluble vitamins and drugs

26
Q

How do fibrates work? eg bezafibrate

A
  • Mechanism not clear
  • Agonists at nuclear hormone receptor- PPAR alpha
  • Increase acitivty of lipoprotein lipase
  • reduce plasma LDL
  • Reduce fibrinogen, reduce coagulation
27
Q

What are the side effects of fibrates?

A

Myositis- muscle inflammation

Rhabdomyolysis- muscle breakdown

28
Q

What does nicotinic acid do? eg acipimox

A

Inhibits hepatic triglyceride production

inhibits VLDL secretion

(lowers lipids)

29
Q

What are the side effects of nicotinic acid?

A

vasodilation- flushing and palpitations

impairs glucose tolerance

causes gout

30
Q

What do fish oils do?

A

mechanisms unclear

high levels of polyunsaturated fats

reduce platelet aggregation

reduce fibrinogen

Drugs (16 decks)

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