Hyperlipidaemia Flashcards
What are some examples of statins?
Atorvastatin
Simvastatin
What are the main actions of statins?
Competitive inhibition of HMG-CoA reductase
Up-regulation of hepatic LDL receptors
Increased clearance of circulating LDL
What are some additional benefits of statin therapy?
Improved vascular endothelial function Stabilisation of atherosclerotic plaque Improved haemostasis Anti-inflammatory Antioxidant
What enzymes metabolise statins?
CYP 3A4
What are some ADRs of statins?
Transient serum transaminase elevation Myalgia - dose related, probs due to interactions w/ other cholesterol lowering agents Can rarely cause rhabdomyolysis GI disturbances Nausea Headache
What should be avoided when taking statins?
Grapefruits - CYP 3A4 inducer
What is an example of a fibrate?
Fenofibrate
Ciprofibrate
How do fibrates exert their effects?
Activation of nuclear transcription factor, PPARα
This regulates expression of genes that control lipoprotein metabolism => increase production of lipoprotein lipase
What are the effects of fibrates?
Enhance clearance of triglycerides
Increase fatty acid uptake by the liver
Increases LDL affinity for receptor
What are indications for prescribing fibrates?
Adjunctive therapy to diet
What are some side effects of taking fibrates?
GI upset Cholesthiasis Myositis Abnormal LFTs Warfarin potentiation
What is another name for nicotinic acid?
Niacin - vitamin B3
How does niacin exert its effects?
Anti-lipolytic => reduced fatty acid supply => decreased triglyceride synthesis
What are some ADRs of niacin?
Flushing Headache Itching Hepatotoxicity GI disturbance
What is an example of cholesterol absorption inhibitors?
Ezetimibe
How do cholesterol absorption inhibitors exert their effects?
Acts at brush border of small intestine mucosa
Reduces absorption of cholesterol from gut by ~50%
Hepatic LDL receptor expression increases
What are some ADRs of cholesterol absorption inhibitors?
Headache
Abdo pain
Diarrhoea
Generally well tolerated
What are examples of monoclonal antibodies used in treatment for hypercholesterolaemia?
Alirocumanb
Evolocumab
How can monoclonal antibodies be used to reduce LDL cholesterol?
Inhibit PCSK9
This protein normally brings to internalised LDL-R which directs for degradation
What are some non-POM options for hypercholesterolaemia?
Plant sterols Fish oils Fibre Vit C/E Alcohol
How do plant sterols act to reduce blood cholesterol?
Structurally similar to cholesterol therefore compete for absorption
Works with statins, but not ezetimibe
Naturally occurring in grains, legumes etc
