Lipid-Lowering Drugs

Question 1

Give two examples of statins

Answer 1

Atorvastatin
Simvastatin
Rosuvastatin
Pravastatin

Question 2

A patient has a lipid profile done and their QRISK score is 12%. They have not had any CVS events.

Should they be on the low or high dose of atorvastatin?

Answer 2

Low - 20mg od

QRISK >10%, and no past CVS events

Question 3

A patient comes for a checkup after having an MI.

Should thay be on a high or low dose of atorvastatin?

Answer 3

High - 80mg od

Past CVS event

Question 4

What is the MoA of statins?

Answer 4

Competitive inhibition of HMG-CoA reductase to reduce the synthesis of cholesterol

Upregulation of LDL receptors to clear circulating LDL

V effective at lowering LDL cholesterol

Question 5

State three additional mechanisms of statins help to prevent CVD risk

Answer 5

1) Stabilises plaques by increasing collagen and reducing SMC proliferation
2) Acts as an anti-inflammatory by reducing CRP and reducing the proliferation of SMCs into plaques
3) Antioxidant by reducing superoxide formation
4) Improved haemostasis by reducing the likliness of clotting and improving clot breakdown

Question 6

Describe how the half-life of simvastatin affects dosing

Answer 6

Short half-life (~2hs)

Therefore take at night as that is when the liver is metabolising cholesterol

Question 7

Describe how the half-life of atorvastatin affects dosing

Answer 7

Long half-life (~30hrs)

Therefore can be taken at any time of day as will still be active at night when the liver is metabolising cholesterol

Question 8

What are the two side-effects of statins?

Answer 8

Myalgia - dose related and worse in combination with amiodarone, other lipid-lowering drugs, and some antibiotics

Rhabdomyalysis (rare)

Question 9

Name two fibrin acid derivatives (fibrates)

Answer 9

Fenofibrate
Ciprofibrate
Gemfibrozil

Question 10

What is the MoA of fibrates?

Answer 10

Activate nuclear transcription factor PPARalpha which:

• Increases the expression of lipoprotein lipase to increase clearance of TGs from lipoproteins
• Increases affinity of LDL for its receptor
• Increases HDL levels

Question 11

What are the effects of fibrates on lipid levels?

Answer 11

Decreases TGs a lot therefore good for pts with high TGs who are at risk of pancreatitis

Decreases LDL by a variable amount

Increases HDL by a fair amount

Question 12

State two side effects of fibrates

Answer 12

GI upset
Cholelithiasis
Abnormal LFTs
Warfarin potentiation

Question 13

What is the MoA of nicotinic acid?

Answer 13

Anti-lipolytic, therefore decreases TG synthesis to:

• Reduce VLDL release and therefore LDL
• Increases HDL (best agent for this)

Question 14

State two side effects of nicotinic acid

Answer 14

Often poorly tolerated, but can be ok with a slow titration up

Flushing
Headache
Itching
Hepatotoxicity
GI symptoms

Question 15

Name a cholesterol absorption inhibitor

Answer 15

Ezetimibe

Question 16

What is the MoA of cholesterol absorption inhibitors?

Answer 16

Reduces the absorption of cholesterol at the brush border (inhibits NPC1L1 transporter)

Increases expression of the LDL receptor at the liver

Good for combination therapy with statins

Question 17

Ezetimibe is a pro-drug and is metabolised by the liver, and stays in the enterohepatic circulation.
What is the benefit of this?

Answer 17

Limits systemic exposure and therefore side effects

Question 18

Alirocumab and evolcumab are used in resistant familial hypercholesterolaemia.
What is the MoA?

Answer 18

When LDL attaches to the receptor on the liver, the complex is internalised.

The MAb’s are PCSK9 inhibitors, and inhibit the degredation of the LDL receptor.

Leads to more LDL receptors to increase the clearance of LDL

Question 19

State two diet changes to manage cholesterol levels

Answer 19

Increased fibre
Fish oils
Vitamin C/E
Plant sterols from legumes and grains

Question 20

What is the target for total cholesterol in secondary prevention?

Answer 20

4.0mmol/L total cholesterol