Hyperlipidaemias

Question 1

Statins - names, mechanism, other benefits, side effects, contraindications

Answer 1

atorvastatin, simvastatin (longer T1/2)
competitive inhibition of HMG-CoA reductase which is a rate controlling enzyme in the mevalonate pathway, causes upregulation of hepatic LDL receptors and increased clearance of circulating LDL

improved vascular endothelial function, stabilisation of atherosclerotic plaque, improved haemostasis, antiimflammatory and antioxidant

GI disruption, headache, myalgia, rarely - rhabdomyolysis

renal impairment, pregnancy&bf, CYP 3A4 - amiodarone, diltiazem, macrolides, amlodipine

Question 2

What are the NICE guidelines for prescribing statins?

Answer 2

1ry prevention - 20mg atorvastatin once daily (10 year CVD risk of >10% using QRISK)
2ry prevention - 80mg
take at night due to circadian rhythms of LDL receptors

Question 3

Fibrates - name, when prescribed?, mechanisms, side effects, contraindications

Answer 3

fenofibrate
usually co prescribed

activation of PPARa to increase production of lipoprotein lipase, increased TAGs from lipoprotein in plasma, increased fatty acid uptake by liver, increased HDL levels

cholelithiasis, myositis

warfarin - bleeding risk

Question 4

Cholesterol absorption inhibitors - name, mechanisms, when prescribed?, side effects, contraindications

Answer 4

ezetimibe

inhibit NPC1L1 transporter which reduces absorption of cholesterol, hepatic LDL receptor expression increases, and is a pro drug so is activated via hepatic metabolism.
prescribed adjunct to statin due to synergistic effects

abdo pain, GI upset

hepatic failure

Question 5

PC5K9 inhibitors - name, mechanism

Answer 5

alirocumab

PC5K9 is a protein which binds to internalised LDL-R directing it for degradation so therefore these cause significant reduction in LDL by preventing internalisation of the receptors