Cholesterol lowering drugs

Question 1

Describe an atheroma

Answer 1

Fatty deposits in the tunica intima covered by a fibrous cap

Question 2

What effects of oxidised LDLs have?

Answer 2

Inhibits macrophage motilityInduces T-cell activation Induces vascular smooth muscle cells divisions and differentiationIt is toxic to endothelial cellsEnhances platelet aggregation

Question 3

Describe the effects of different types of lipids

Answer 3

HDLs - reduces CHD riskLDLs - links to coronary atherosclerosis

Question 4

What are the different types of drugs which can be used to lower levels of lipids?

Answer 4

StatinsCholesterol absorption inhibtorsFibratesNiacinBile acid sequestrants

Question 5

Describe the transport function of chylomicrons

Answer 5

Dietary TAGs from intestine to the tissues (adipose)

Question 6

Describe the transport function of VLDLs

Answer 6

Dietary TAGs synthesised in the liver to adipose for storage

Question 7

Describe the transport function of LDLs

Answer 7

Cholesterol synthesised in the liver to the tissues

Question 8

Describe the transport function of HDLs

Answer 8

Excess tissue cholesterol to the liver so its can be disposed as biles salts

Question 9

Which of the lipoproteins causes the worst clinical effects?

Answer 9

LDLs

Question 10

Which is the most commonly used lipid lowering drug and why/

Answer 10

Statins- cheap- best tolerated for lowering LDLs- is very effective

Question 11

What is the primary physiological action of statins?

Answer 11

Inhibits hepatic HMG CoA Reductase- involved in cholesterol synthesis

Question 12

What happens when the hepatic cholesterol concentration decreases?

Answer 12

This stimulates LDL receptor production which increase the rate of removal of LDLs from the plasma

Question 13

Describe simvastatin

Answer 13

Has a short half lifeMost commonly used statinGiven at night so have highest conc at time when cholesterol production is greatest

Question 14

Describe atorvastatin

Answer 14

Half life = 20 hoursHas a superior efficacy to simvastatin

Question 15

Describe rostuvastatin

Answer 15

Contains sulphurIs more potent than simvastatinHalf life = 20 hours

Question 16

What is the indication for prescription for statins?

Answer 16

Hyperlipidaemia which has not responded to changes in diet or exercise

Question 17

When would you not give a statin?

Answer 17

Pregnant womenBreastfeeding womenPt with liver disease

Question 18

Give some adverse drug reactions which occur with statins

Answer 18

Increase transaminase levelsMyopathyGI disturbancesArthralgiaHeadaches

Question 19

Describe myopathy and when would you get it

Answer 19

Diffuse muscle pain- when combining statin use with cyclosporin, erythromycin, niacin- can test levels of creatinine kinase to confirm presence of myopathy

Question 20

What is the mechanism of action of fibrates?

Answer 20

Act as agonists on the Peroxisome Proliferator-Activated Receptor-α (PPAR-α).

Question 21

What actions do fibrates have?

Answer 21

• LDL lowering (variable amount)- HDL increases of 15-25% in hypertriglyceridemia- Decreases Triglycerides 25-50%

Question 22

When would you prescribe fibrates?

Answer 22

Used as first line choice in hypertriglyceridemia

Question 23

Give some examples of fibrates

Answer 23

BezafibrateCiprofibrateGemfibrozil

Question 24

When would you not use fibrates?

Answer 24

PregnancyBreast feedingGall bladder diseaseSevere renal of hepatic impairmentHypoalbuminaemia

Question 25

What are some ADRs which occur with fibrates?

Answer 25

GI disturbancesDermatitisPruritisRashImpotenceHeadacheDizzinessBlurred vision

Question 26

Describe cholesterol absorption inhibitors

Answer 26

Inhibit cholesterol uptake by blocking NPC1L1 (cholesterol transport uptake protein) in the brush border. This decrease the hepatic cholesterol concentration.

Question 27

Give an example of a cholesterol uptake inhibitor

Answer 27

Ezetimibe

Question 28

What kind of effect does a dose of ezetimibe have?

Answer 28

A single 10mg dose reduces LDL levels by 15-20%.

Question 29

When would you use ezetimibe?

Answer 29

In statin intolerant patients- can give with a statin to reduce LDL levels by 40% and to reduce the side effects of statins

Question 30

What are some adverse drug reactions for cholesterol uptake inhibitors?

Answer 30

GI disturbances- diarrhoea- painHeadache

Question 31

Describe the mechanism of action of bile acid sequestrants

Answer 31

Bind to bile acids in the intestine and prevent their reabsorption which means that there will be lower cholesterol levels as bile acids are produced from cholesterol.

Question 32

Give some ADRs for bile acids sequestrants

Answer 32

GI disturbances- nausea- vomiting- constipation- abdominal pain- flatulence- heart burn

Question 33

When would you not use bile acid sequestrants?

Answer 33

Biliary obstruction

Question 34

Give the mechanism of action of niacin

Answer 34

Inhibits lipoprotein-a synthesis

Question 35

What are the effects of niacin?

Answer 35

Increases HDL levels- decreases risk of cardiovascular events

Question 36

Give some side effects of niacin

Answer 36

Skin flushingItchingDry skinEczema exacerbationsAcanthosis nigricans