1. Antilipidaemic agents
Reference : a textbook of clinical pharmacology and therapeutics
Antilipidaemic agents
Dr A. W Olusanya

2. Introduction
Hyperlipidaemia
Dyslipidaemia
Aetiology – Diet, genetics

3. Intro Risk factor for cardiovascular diseases
Pancreatitis - High – triglyceride

4. Treatment
Pharmacological
Non pharmacological

5. Sites of action of lipid lowering drugs
Reference : a textbook of clinical pharmacology and therapeutics
Sites of action of lipid lowering drugs

6. Drugs used in treating hyperlipidaemia
Statins
Bile acid sequestrants
Fibrates
Nicotinic acid
Ezetimibe
Other agents

7. Statins Rosuvastin Artovastatin Simvastatin
pravastatin, lovastatin, fluvastatin
Cerivaststin – withdrawn, drug interactions and rhabdomyolysis
Rosuvatatin – less drug interaction – not metabolised by cyt p450

8. Statins HMG CoA reductase inhibitor.
Enzyme responsible for conversion of HMG –CoA to mevalonate
Rate limiting step rate limiting enzyme in the synthesis of cholesterol in the liver
Reduction in cytoplasmic cholesterol levels leads to upregulation of LDL receptors to compensate for reduced cholesterol
Therefore reducing plasma levels of LDL
More active at night

9. Significant LDL lowering and total cholesterol lowering effects
Modest triglyceride lowering and HDL raising effect

10. Other effects Regression of atherosclerosis Anti-inflammatory
Antioxidant
Plaque stabilizing effect

11. Adverse effects
Rhabdomyolysis,myalgia
Hepatitis
Angioedema

12. Bile acid sequestrants
Anion exchange compound
Reduces LDL cholesterol, and a small increase in HDL
Increase in triglyceride
Reduces the absorption of statins and other drugs
Adverse effect – constipation, reduces absorption of other drugs
Cholestyramine, colestipol, colesevelam,

13. Colesevelam Newest , better – less constipation, less drug interaction
No effect on triglyceride and HDL

14. Nicotinic acid/Niacin
Lowers LDL and triglycerides
Significantly raises HDL
Binds to G-protein coupled receptor to inhibit production of cAMP
Leading to reduced generation of FFA- reduced hepatic secretion of lipids
May increase risk of myopathy when used with statins
Adverse effects – hepatotoxic, flushing, itching, rash

15. Fibric acid derivatives
Gemfibrozil, fenofibrate, bezafibrate
Lowers triglyceride and increases HDL,
Negligible LDL lowering effect
Peroxisome proliferator-activated receptor-α (nuclear receptor co- activator) activator – reducing hepatic VLDL and also stimulate lipoprotein lipase (reducing TG)
Increases the risk of myositis if given with statins

16. Ezetimibe
Inhibits absorption of sterols at the brush border of the intestinal lumen
Reduces LDL cholesterol, reduces triglyceride and a small increase in HDL
Does not interfere with absorption of other drugs, no constipation

17. Other agents Lomitapide – Mipomersem -
Fish oil – polyunsaturated fatty acid
PCSK9 inhibitors – Proprotein convertase subtilisin/kesin type 9
alirocumab, evolocumab

18. Non pharmacological
Diet
Exercise