3. Cholesterol lowering drugs

Question 1

how do statins reduce cholesterol

Answer 1

Inhibit HMG-CoA reductase in hepatocytes:

1. reduced cholesterol, VLDL and LDL synthesis
2. increased LDL R synthesis… increased plasma IDL and LDL clearance
3. increased HDL

Question 2

describe 4 secondary benefits of statins in CVD prevention

Answer 2

1. anti-inflammatory
2. reduced plaque
3. reduced thrombotic risk
4. increased endothelial cell function

Question 3

describe 3 indications for statin therapy

Answer 3

1. familial hyprecholesterolaemia
2. primary CVD prevention in those with >10% 10yr risk of CVD dev. (QRISK2 assessment tool)
3. secondary prevention in Ps with CVD

Question 4

what is the aim of statin therapy

Answer 4

> 40% in non-HDL cholesterol

Question 5

describe the main adverse effects of statin therapy

Answer 5

Uncommon

1. increased transaminase levels
2. myopathy: diffuse muscle pain and increased CK, rarely can progress to rhabdomyolysis
3. GI disturbances, arthralgias and headaches

Question 6

with which drugs can statins interact to worsen adverse effects

Answer 6

cyclosporin or erythromycin

gemfibrozil or niacin

Question 7

what is the drug of choice is statins aren’t tolerated

Answer 7

ezetimibe

Question 8

what is the MOA of ezetimibe

Answer 8

cholesterol lipase inhibitor - lowers plasma cholesterol by:
1. decreasing cholesterol absorption from small intestine
2, decreased cholesterol delivery to hepatocytes - must take up more from circulation

Question 9

which drugs can be used to specifically target plasma [TAG] - what is its MOA

Answer 9

Fibric acid derivatives (eg gemfibrozil) - PPAR-a agonists that increase lipoprotein lipase production… decreased TAG production

Also cause variable decrease in LDL and increase in HDL

Question 10

describe the MOA of nicotinic acids (niacin)

Answer 10

stimulate lipoprotein a synthesis… decreased VLDL and increased HDL-C

Question 11

describe the possible adverse effects of nicotinic acids

Answer 11

1. flushing, itching, headache
2. hepatotoxicity
3. peptic ulcer activation
4. hyperglycaemia and decreased insulin sensitivity

Question 12

name and describe the MOA of a mAb used in treatment of dyslipidaemia/CVD

Answer 12

Evolocumab - PCSK9 inhibitor

PCSK9 normally binds and promotes LDL R breakdown (increasing plasma LDL) levels so inhibition of this protein promotes cellular LDL uptake via LDL R