Lipid and Cholesterol Metabolism

Question 1

Outline the pro-atherogenic effects of OX-LDL

Answer 1

Inhibits macrophage motility

Induces T-cell activation and VSMC division / differentiation

Toxic to endothelial cells

Enhances platelet aggregation

Question 2

How is cholesterol synthesised?

Answer 2

In the liver

Starts with acetyl-CoA

Requires HMG-CoA synthase and reductase

Question 3

Recognise the main drug groups used in reducing LDL cholesterol

Answer 3

Statins = simvastatin

Cholesterol lipase inhibitors = ezetimibe

Nicotinic acid / niacin

Fibrates = fenofibrate

Resins = colestyramine

Omega-3 FA = omacor

Question 4

Discuss statins

Answer 4

Inhibit cholesterol synthesis in hepatocytes = block HMG-CoA reductase

Increase clearance of IDL and LDL – make sure receptors are still valid

Decrease production of VLDL and LDL

Question 5

What are the indication for the use of statins?

Answer 5

CV risk prevention (CVD + DM)

Familial hypercholesterolaemia

Question 6

What are the adverse side effects of statins?

Answer 6

Liver damage - increased transaminase levels

Myopathy – pains in joints and muscles

Question 7

Name some secondary benefits of statin treatment

Answer 7

Anti-inflam

Plaque reduction

Improved endothelial cell function

Reduced thrombotic risk

Question 8

Describe fibric acid derivatives

Answer 8

Mechanism = increases prod of lipoprotein lipase = reduces TG prod, SMALL reduction in LDL

Indication = adjunctive to diet, hypertriglyceridemia

ADR = GI upset, myositis, abnormal LFTs

Question 9

Describe nicotinic acid

Answer 9

Mechanism = inhib lipoprotein a synthesis = reduced VLDL, increases HDL

Indication = risk of coronary events

ADR = flushing (taken with aspirin), itching, headache, hepatotoxicity

Question 10

Describe ezetimibe?

Answer 10

Mechanism = inhibits intestinal cholesterol absorption, increase hepatic LDL receptors

ADR = headache, abdo pain, diarrhoea

Question 11

Describe evolocumab

Answer 11

Monoclonal Ab

PCSK9 inhibitor = inhibits proprotein convertase

Treats primary hypercholesterolaemia or mixed dyslipidaemia as adjunct to diet

Question 12

Recognise the potential for non-drug dietary approaches to lipid lowering

Answer 12

Good diet has great impact on TG

Plant sterols – yogurts, flora

Diet rich in = fish oils, fibres, vit C/E

Question 13

outline how to undertake a CV risk assessment

Answer 13

QRISK2

Age

Gender

Ethnicity

Postcode

Clinical info = smoking, DM, angina, CDK, AF, BP treatment, RA

Question 14

Outline the NICE guidance pertaining to lipid-lowering drug prescribing

Answer 14

Statin - recommend as primary prevention of CVD for adults who have a 20% or greater 10 year risk of devel CVD