Lipid-Lowering Drugs Flashcards
Give two examples of statins
Atorvastatin
Simvastatin
Rosuvastatin
Pravastatin
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?
Low - 20mg od
QRISK >10%, and no past CVS events
A patient comes for a checkup after having an MI.
Should thay be on a high or low dose of atorvastatin?
High - 80mg od
Past CVS event
What is the MoA of statins?
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
State three additional mechanisms of statins help to prevent CVD risk
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
Describe how the half-life of simvastatin affects dosing
Short half-life (~2hs)
Therefore take at night as that is when the liver is metabolising cholesterol
Describe how the half-life of atorvastatin affects dosing
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
What are the two side-effects of statins?
Myalgia - dose related and worse in combination with amiodarone, other lipid-lowering drugs, and some antibiotics
Rhabdomyalysis (rare)
Name two fibrin acid derivatives (fibrates)
Fenofibrate
Ciprofibrate
Gemfibrozil
What is the MoA of fibrates?
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
What are the effects of fibrates on lipid levels?
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
State two side effects of fibrates
GI upset
Cholelithiasis
Abnormal LFTs
Warfarin potentiation
What is the MoA of nicotinic acid?
Anti-lipolytic, therefore decreases TG synthesis to:
- Reduce VLDL release and therefore LDL
- Increases HDL (best agent for this)
State two side effects of nicotinic acid
Often poorly tolerated, but can be ok with a slow titration up
Flushing Headache Itching Hepatotoxicity GI symptoms
Name a cholesterol absorption inhibitor
Ezetimibe
What is the MoA of cholesterol absorption inhibitors?
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
Ezetimibe is a pro-drug and is metabolised by the liver, and stays in the enterohepatic circulation.
What is the benefit of this?
Limits systemic exposure and therefore side effects
Alirocumab and evolcumab are used in resistant familial hypercholesterolaemia.
What is the MoA?
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
State two diet changes to manage cholesterol levels
Increased fibre
Fish oils
Vitamin C/E
Plant sterols from legumes and grains
What is the target for total cholesterol in secondary prevention?
4.0mmol/L total cholesterol
