Hyperlipidaemia

Question 1

What are some examples of statins?

Answer 1

Atorvastatin

Simvastatin

Question 2

What are the main actions of statins?

Answer 2

Competitive inhibition of HMG-CoA reductase
Up-regulation of hepatic LDL receptors
Increased clearance of circulating LDL

Question 3

What are some additional benefits of statin therapy?

Answer 3

Improved vascular endothelial function 
Stabilisation of atherosclerotic plaque 
Improved haemostasis 
Anti-inflammatory 
Antioxidant

Question 4

What enzymes metabolise statins?

Answer 4

CYP 3A4

Question 5

What are some ADRs of statins?

Answer 5

Transient serum transaminase elevation 
Myalgia - dose related, probs due to interactions w/ other cholesterol lowering agents 
Can rarely cause rhabdomyolysis 
GI disturbances 
Nausea 
Headache

Question 6

What should be avoided when taking statins?

Answer 6

Grapefruits - CYP 3A4 inducer

Question 7

What is an example of a fibrate?

Answer 7

Fenofibrate

Ciprofibrate

Question 8

How do fibrates exert their effects?

Answer 8

Activation of nuclear transcription factor, PPARα

This regulates expression of genes that control lipoprotein metabolism => increase production of lipoprotein lipase

Question 9

What are the effects of fibrates?

Answer 9

Enhance clearance of triglycerides
Increase fatty acid uptake by the liver
Increases LDL affinity for receptor

Question 10

What are indications for prescribing fibrates?

Answer 10

Adjunctive therapy to diet

Question 11

What are some side effects of taking fibrates?

Answer 11

GI upset 
Cholesthiasis 
Myositis
Abnormal LFTs 
Warfarin potentiation

Question 12

What is another name for nicotinic acid?

Answer 12

Niacin - vitamin B3

Question 13

How does niacin exert its effects?

Answer 13

Anti-lipolytic => reduced fatty acid supply => decreased triglyceride synthesis

Question 14

What are some ADRs of niacin?

Answer 14

Flushing 
Headache 
Itching 
Hepatotoxicity 
GI disturbance

Question 15

What is an example of cholesterol absorption inhibitors?

Answer 15

Ezetimibe

Question 16

How do cholesterol absorption inhibitors exert their effects?

Answer 16

Acts at brush border of small intestine mucosa
Reduces absorption of cholesterol from gut by ~50%
Hepatic LDL receptor expression increases

Question 17

What are some ADRs of cholesterol absorption inhibitors?

Answer 17

Headache
Abdo pain
Diarrhoea

Generally well tolerated

Question 18

What are examples of monoclonal antibodies used in treatment for hypercholesterolaemia?

Answer 18

Alirocumanb

Evolocumab

Question 19

How can monoclonal antibodies be used to reduce LDL cholesterol?

Answer 19

Inhibit PCSK9

This protein normally brings to internalised LDL-R which directs for degradation

Question 20

What are some non-POM options for hypercholesterolaemia?

Answer 20

Plant sterols 
Fish oils 
Fibre 
Vit C/E
Alcohol

Question 21

How do plant sterols act to reduce blood cholesterol?

Answer 21

Structurally similar to cholesterol therefore compete for absorption
Works with statins, but not ezetimibe

Naturally occurring in grains, legumes etc