1. By: Dr Israa Omar MBBS, MRCP, MSc pharmacology
Lipid lowering agents
By: Dr Israa Omar
MBBS, MRCP, MSc pharmacology

2. HMG-CoA reductase inhibitors
Reduces plasma concentration of LDL- Cholestrol by more than 30%.
Also cause a small reduction on plasma TGA and a small increase in plasma HDL
(statins)include simvastatin, pravastatin, atorvastatin.
REDUCE THE RISK OF CORONARY RTERY DISEASE BY 42%

3. MOA
Suppress HMG-COA reductase in the liver and therefore depress the production of cholesterol, which leads to increase synthesis of LDL receptors .
As a result, the clearance of LDL is enhanced

4. Clinical uses
To treat patient with hyperlipidemia

5. Adverse effects GIT disturbance Insomnia Rash
More serious adverse effects (myositis, hepatitis, angio-oedema )

6. fibrates Include clofibrate, gemofibrate, fenofibrate.
Mainly reduce VLDL and hence triglyceride .
Also reduce LDL and increase HDL
Gemofibrozil has been shown to reduce coronary heart disease by one third compared to the placebo in male patients with primary hyperlipidaemia

7. MOA
Stimulate the lipoprotien lipase in the peripheral tissues, and hence, increase hydrolysis of TGA in chylomicron and VLDL particles.
Also probably reduce hepatic VLDL production and increase LDL uptake

8. Clinical uses
To treat patients with mixed hyperlipidemia (raised TGA and raised cholestrol)

9. Adverse effects
Myositis which can cause myoglobinuria and acute renal failure
Clofibrate can cause gallstone so its use is limited to patients who have had cholcystomy

10. Bile acid-binding resins
Cholestyramine and Colestipol
They reduce the plasma concentration of LDL-cholestrol by more than 10%

11. MOA
They sequester the bile in the intestine and prevent their reabsorption and entero- hepatic recirculation.
This lead to increase expression of LDL receptors in the liver and hence removal of LDL from the blood

12. Clinical uses
Used in addition to statins to treat hyperlipidemia

13. Adverse effect
N/V, abdominal pain , bloating, constipation or diarrhea are the commonest adverse effects
They interfere with absorption of fat- soluble vitamins and drugs like Digoxin and Warfarin

14. Nicotinic acid derivatives
Mechanism of action is poorly understood
It is a water soluble vitamin
Inhibit the production of hepatic triglyceride and VLDL secretion with reduction of in TGA and LDL and increase HDL
It increase the blood sugar and causes flushing of the face an effect that can be reduced by taking Aspirin
Modified release prepartion are well tolerated

15. Ezetimibe
Specifically inhibits absorption of cholesterol by blocking NPC1L1 in the brush border without affecting the absorption of bile salts or fat soluble vitamins
Combined with statins to treat patients with severe dyslipidemia
Generally well tolerated but can cause diarrhea, headache, rash and angioedema also reported

16. Thank you

17. Reference
RANGE AND DALE ,PHARMACOLOGY