Hyperlipidaemias

Question 1

For individuals with high cholesterol, what would be the first line treatment?

Answer 1

Lifestyle modification:

• weight loss
• exercise
• plant sterols
• fibre in diet

Question 2

What is typically the first line agent offered for hypercholesterolemia and its actions?

Answer 2

Statins - they work by blocking the malvonate pathway at HMG-coA. This reduces the amount of hepatic cholesterol within the cell and therefore upregulates LDL receptors on the cell surface. Also causes a decrease in VLDL secretion.

Question 3

Why are statins taken at night?

Answer 3

The liver is more active at night, therefore more cholesterol is sequestered.

Question 4

What are the additional benefits of statin therapy?

Answer 4

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

Question 5

Why is atorvastatin more commonly prescribed than simvastatin?

Answer 5

Simvastatins half life is around 2 hours after first pass metabolism
Atorvastatins half life is around 30 hours after first pass metabolism

Question 6

What side effects are indicated in statin use?

Answer 6

GI disruption, nausea 
Headache 
Myalgia 
Dose related 
Rarely have rhabdomyolysis

Question 7

Which medical conditions should be of concern when prescribing statins?

Answer 7

Renal impairment
Pregnancy and breastfeeding
Amiodarone, diltiazem, macrolides and amlodipine - impair CYP 3A4

Question 8

For primary prevention of CVD what drug and dose should be prescribed?

Answer 8

20mg atorvastatin once daily

Question 9

For secondary prevention of CVD, what dosage and drug should be prescribed?

Answer 9

Atorvastatin 80mg once daily

Question 10

How do fibric acid derivatives work?

Answer 10

Activate of nuclear transcription factor PPARa - regulates expression of genes controlling lipoprotein metabolism increasing LPL production.

Therefore more TGs from lipoprotein in plasma and increased FA uptake by liver. Increased HDL levels.

Question 11

What side effects are there for fibrates?

Answer 11

Cholelithiasis and myositis

Question 12

What drug considerations should be accounted for with fibrates?

Answer 12

Warfarin

Question 13

What two drugs can be co-prescribed with a statin to aid in reducing cholesterol?

Answer 13

Fenofibrate (fibrates)

Ezetimibe (NPC1L1 transport inhibitor)

Question 14

How does ezetimibe work?

Answer 14

It inhibits NPC1L1 transporter, reducing absorption of cholesterol by the GIT by 50%

Hepatic LDL receptor expression increases

It is a pro-drug and enters the enterohepatic circulation. It is secreted by bile and therefore has good tolerability.

Question 15

What contraindications and cautions should be aware of when prescribing ezetimibe?

Answer 15

Contraindications-abdominal pain, GI upset

Cautions- hepatic failure

Question 16

For those being treated for secondary prevention what is the target?

Answer 16

2. 0 mmol/L LDL

4. 0mmol/L total

Question 17

How does alirucumab/evolocumab work?

Answer 17

PCSK9 is a protein which binds internalised LDL-R directing them to degradation. By blocking them, there is a significant reduction in LDL cholesterol.

These are called - alirocumab and evolocumab