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Lipid lowering agents. By: Dr Israa Omar MBBS, MRCP, MSc pharmacology. 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
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Lipid lowering agents By: Dr Israa Omar MBBS, MRCP, MSc pharmacology
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%
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
Clinical uses • To treat patient with hyperlipidemia
Adverse effects • GIT disturbance • Insomnia • Rash • More serious adverse effects (myositis, hepatitis, angio-oedema )
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
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
Clinical uses • To treat patients with mixed hyperlipidemia (raised TGA and raised cholestrol)
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
Bile acid-binding resins • Cholestyramine and Colestipol • They reduce the plasma concentration of LDL-cholestrol by more than 10%
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
Clinical uses • Used in addition to statins to treat hyperlipidemia
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
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
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
Reference • RANGE AND DALE ,PHARMACOLOGY