Hyperlipidaemia

Question 1

Atorvastatin/simvastatin

Answer 1

Indication: hyperlipidaemia

Class: statin

Action:
- competitive inhibition of HMG- CoA reductase
- upregulation of hepatic LDL receptors
- increased clearance of circulating LDL
- decrease secretion of VLDL

Dose:
- primary prevention 20mg
- secondary prevention 80mg

Adverse effects:

• GI disruption, nausea, headache
• myalgia
• rhabdomylosis

Warnings:

• renal/hepatic impairement
• pregnancy and breastfeeding

Interactions:

• amlodipine - increases plasma statin
• amiodarone, macrolides - increase statin (CYP3A4 inhibtion)
• grapefruit juice inhibits CYP3A4

Other:

• simvastatin - prodrug activated by FPM - short half life
• atorvastatin - FPM produces further active metabolites - long half life

Question 2

Fenofibrate

Answer 2

Indication: hyperlipideamia

Class: fibric acid derivatives

Action: activation of nuclear transcription factor PPARa - increase production of lipoprotein lipase

• increase triglyceride removal from lipoprotein in plasma
• increase fatty acid uptake by liver
• increase levels of HDL
• increase LDL affinity for receptor

Adverse effects:

• gall stones (avoid w/ gall bladder disease)
• GI upset
• myositis
• photosensitivity

Interactions: warfarin - increase anticoagulation

Question 3

Ezetimibe

Answer 3

Indication: hyperlipideamia

Class: cholesterol absoprtion inhibitors

Action:

• inhibit NPC1L1 transporter at brush border in SI
• redcues absorption of cholesterol by gut
• increase expression of hepatic LDL receptor
• prodrug, hepatic metabolism, enterohepatic circulation, limits systemic exposure, secreted by bile

Adverse effects:

• abdo pain, GI upset
• angioedema

Warning: hepatic failure - pro drug so part of hepatic metabolism and enterohepatic circulation

Interactions:

• mindful with statin - increased risk of rhabdomyloysis
• ciclosporin - increases ezetimibe

Other: adjunct to statin

Question 4

Alirocumab

Answer 4

Indication: hyperlipideamia

Class: monoclonal antibody

Action: PCSK9 inhibitor - prevents internalisation and degradation of LDL receptors - more LDL absorbed from the blood

Adverse effects:

• long term effects unknown
• requires lifetime injections

Question 5

Inclisiran

Answer 5

Indication: hyperlipideamia

Class: siRNA

Actions: inhibits hepatic translation of PCSK9 so prevents internalisation and degradation of LDL receptors - more LDL absorbed from the blood

Adverse effects:

• long term effects unknown
• requires lifetime injections