Antilipidaemics Flashcards
Classes of antilipidaemics
Statins
Bile acid sequestrants
Fibrates
Nicotinic acid
Ezetimibe
PCSK9 inhibitors
Omega 3 fatty acids
Lomitapide
Mipomersen
Effects of statins on TG, LDL, HDL
- Significant LDL lowering and total cholesterol lowering effects
- Modest triglyceride lowering
- Modest HDL raising effect
Examples of statins based on potency
- High potency - Rosuvastatin, Artovastatin
- Intermediate potency - Simvastatin
- Low potency - Pravastatin, Lovastatin, Fluvastatin
Statins MOA
Statins act in the liver to inhibit HMG CoA reductase, the enzyme responsible for the conversion of 3-hydroxy-3-methoxy glutaryl –CoA to mevalonate.
This is the rate limiting step in the synthesis of cholesterol in the liver. This leads to reduced endogenous production of cholesterol.
Reduction in cytoplasmic cholesterol levels leads to upregulation of LDL receptors in the liver. This results in enhanced uptake of LDL cholesterol in the circulation thus reducing plasma levels of LDL.
Why are statins administered at night?
The enzyme is more active at night
Which statins don’t necessarily need to be administered at night?
rosuvastatin and artovastatin, which are high potency statins.
Pleiotropic effects of statins
Regression of atherosclerosis
Anti-inflammatory
Plaque stabilizing effect
Improved endothelial function
Antioxidant
Adverse effects of statins
- Major adverse effect include rhabdomyolysis, hepatitis, and angioedema
- Others include headache, nausea, bowel upset, sleep disturbances and rashes.
Examples of bile acid sequestrants
Cholestyramine
Colestipol
Colsevelam
Bile acid sequestrants MOA
These are basic anion exchange compound.
They bind to bile acids in the intestine thus reducing the absorption of lipids. This leads to increased faecal excretion of bile salts and cholesterol.
Effects of BAS on TG, LDL, and HDL
- Reduces LDL cholesterol
- Small increase in HDL
- Increase in triglyceride
DI and adverse effects of BAS
Reduces the absorption of statins and other drugs
Adverse effect – constipation, flatulence,
Niacin MOA
- It reduces the production of VLDL in the liver by inhibiting triglyceride synthesis. This leads to reduced production of IDL and LDL cholesterol.
- It also reduces the rate of lipolysis in adipose tissue, reducing the transport of free fatty acids to the liver and decreasing hepatic TG synthesis.
- It increases the activity of lipoprotein lipase that clears triglycerides
Effects of niacin on TG, LDL, and HDL
TG - significantly reduced
LDL - significantly reduced
HDL - relatively increased
Adverse effects of niacin
- Hepatotoxic, flushing, itching, rash, dyspepsia, nausea
- Others are liver dysfunction, jaundice, hyperglycaemia
- May increase risk of myopathy when used with statins
Examples of fibrates
Gemfibrozil, Fenofibrate, Benzafibrate
Effects of fibrates on TG, LDL, and HDL
- Lowers triglyceride
- Increases HDL
- Negligible LDL lowering effect
Fibrates MOA
- Interact with PPARs to reduce TG by stimulation of fatty acid oxidation
- Stimulate lipoprotein lipase to reduce TG
What is PPAR-alpha and how does it affect lipid metabolism?
It is the peroxisome proliferator-activated receptor, a nuclear receptor co-activator that regulates gene transcription for lipid metabolism. It also stimulates lipoprotein lipase.
Adverse effects of fibrates
Increased risk of myositis with statins
Ezetimibe MOA
Inhibits absorption of cholesterols at the brush border of the intestinal lumen
Effect of ezetimibe on LDL, HDL, TG
Reduces LDL cholesterol
Reduces triglyceride
Small increase in HDL
PCSK9 inhibitors examples
Alirocumab
Evolocumab
PCSK9 meaning
Proprotein convertase subtilisin/kesin type 9)
PCSK9 inhibitors MOA
They inhibit the PCSK9 enzyme that binds to LDL receptors on hepatocytes, leading to receptor degradation. Its inhibition means more receptors are available to clear plasma LDL.
Mipomersen MOA
Inhibits apo B-100 synthesis, lowers LDL
Lomitampide MOA
Inhibits microsomal TG transfer protein, essential for VLDL formation
Fish oil MOA
Reduces VLDL triglycerides
