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MD2002 > Cholesterol Lowering Drugs > Flashcards

Cholesterol Lowering Drugs Flashcards

1
Q

what are the 5 main classes of lipoproteins?

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

what do chylomicrons do?

A

transport TG and cholesterol esters from GI to tissues

- split by lipoprotein lipase to release free fatty acids (FFAs)

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3
Q

where are chylomicron remnants taken up?

A

the liver

- cholesterol stored, oxidised to bile acids or released to VLDL

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4
Q

what does VLDL do?

A

transports cholesterol and newly synthesised TG to tissues

- TGs removed from VLDL leaving LDL with a high cholesterol (taken up by cells or liver)

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5
Q

what is the relationship between plasma cholesterol and LDL?

A

increased plasma cholesterol associated with increased LDL is a risk factor for atheromatous disease
- may lead to atherosclerosis, ischaemic heart disease, MI and cerebral vascular incidents

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6
Q

what is the term for an increase in plasma concentration of lipids?

A

hyperlipidaemia

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7
Q

what is the average total cholesterol level in UK?

A

5.7mmol/l

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8
Q

what is the ideal level of total cholesterol?

A

<5mmol/l

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9
Q

what is the aim of lipid lowering drugs?

A

to reduce plasma cholesterol by:

+ reducing production of lipoproteins
OR
+ increasing lipoprotein removal from blood

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10
Q

what 3 sources is cholesterol derived from?

A

+ de novo synthesis in liver
+ uptake from circulating LDLs
+ uptake of chylomicron remnants

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11
Q

what is the main action of colestyramine?

A

to sequester bile acids in the intestine/decrease hepatic stores of cholesterol

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12
Q

what is the main action of ezetimibe?

A

to inhibit the transport protein for cholesterol in the brush border of enterocytes in the duodenum

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13
Q

what is the main action of fibrates?

A

to alter the levels of plasma lipoproteins

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14
Q

what is the main action of simvastatins, pravastatins, atorvastatins and rosuvastatins?

A

to inhibit the synthesis of cholesterol in liver

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15
Q

what is colestyramine?

A

a basic anion exchange resin:

  • sequesters bile acids to prevent enterohepatic recirculation
  • ∴↑ metabolism of endogenous cholesterol into bile acids
  • ↑LDL receptor numbers in liver resulting in removal of LDLs from blood
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16
Q

what combination can lower blood cholesterol by 50%?

A

bile-sequestering drugs plus inhibitors of cholesterol biosynthesis

17
Q

what are examples of fibrates?

A

+ fenofibrates
+ bezafibrates
+ gemfibrozils

18
Q

how do fibrates work?

A

+↓plasma triglycerides and, to a lesser extent, cholesterol

+ particularly ↓ elevated concentrations of VLDL

+ main action is stimulation of lipoprotein lipase
which ↓ the triglyceride content of VLDL

+ clearance of LDL by the liver is also stimulated

+ ↑ HDL production and reverse cholesterol transport

19
Q

what are clinical uses of fibrates?

A

+ mixed dyslipidaemia (raised serum triglyceride as well as cholesterol)

+ in patients with low HDL and high risk of atheromatous diease (type 2 diabetes)

+ combined with other lipid-lowering drugs for severe treatment resistant dyslipidaemia

20
Q

what is an example of a nicotinic acid?

A

niacin

21
Q

what are nicotinic acids?

A

vitamin with lipid-lowering properties:

  • ↓ VLDL production which leads to ↓ in LDL
  • also activates lipoprotein lipase
22
Q

what does an ezetimibe do?

A

specifically reduces intestinal cholesterol absorption

- inhibits a sterol carrier protein in brush border of enterocytes

23
Q

what are statins?

A

hydroxymethlglutamyl-coenxyme A reductase (HMG-CoA reductase) inhibitors

24
Q

what does HMG-CoA reductase do?

A

+ major rate-limiting step in cholesterol synthesis

+ converts HMG-CoA to mevalonic acid (MVA)

25
Q

what are examples of statins?

A

simvastatin, pravastatin, atorvastatin, rosuvastatin - long lasting HMG-CoA reductase inhibitors

26
Q

what are clinical uses of statins?

A

+ primary prevention of arterial disease in patients with high serum cholesterol

+ secondary prevention of MI and stroke in those who have atherosclerotic diseases

+ atorvastatin lowers serum cholesterol in familial hypercholesterolaemia

27
Q

what are side effects of statins?

A

can cause:

  • myositis
  • angio-oedema
  • GI disturbances
  • insomnia
  • rash
28
Q

what are side effects of fibrates?

A

can cause:

  • myositis (esp. in patients with renal impairment)
  • GI disturbances
29
Q

what are side effects of colestyramine and ezetimibe?

A

can cause GI symptoms:

  • nausea
  • abdominal bloating
  • constipation
  • diarrhoea
30
Q

what are side effects of nicotinic acids?

A

can cause:

  • flushing
  • palpitations
  • GI disturbances

MD2002 (85 decks)

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