By: Dr Israa Omar MBBS, MRCP, MSc pharmacology 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

Thank you

Reference RANGE AND DALE ,PHARMACOLOGY