anti-hyperlipidemic抗动脉粥样硬化药.pptVIP

Antiatherosclerotic Agents抗动脉粥样硬化药 Formation of Atherosclerotic Plaques Therapeutic Strategies Regulation of lipid Antioxidation Protection of arterial endothelium Others: Cholesterol and Triglyceride Metabolism De Novo Cholesterol Biosynthesis Liver synthesizes 2/3 of cholesterol made by the body. The rate limiting enzyme is 3-hydroxyl 3-methyl glutaryl (HMG)-CoA reductase. Bile acids are synthesized from cholesterol in the liver, released into the intestine and reabsorbed in the jejunum and ileum Lipoprotein Disorders OR: HDL concentration＜normal Regulators of lipoproteins’ levels 1. Competitive inhibitors of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase: lovastatin (洛伐他汀), mevastatin(美伐他汀), pravastatin (普伐他汀), simvastatin (辛伐他汀), fluvastatin (氟伐他汀). Lovastatin Mechanism of action: analogues of HMG-CoA, inhibits HMG-CoA reductase increases high-affinity LDL receptors, promotes catabolism of LDL inhibits synthesis of cholesterol in the liver. Uses Hypercholesterolemia, patients with elevating plasma of LDL. first choice for essential hypercholesterolemia, heterozygous familial hypercholesterolemia. It should not be given to children or teenage. Adverse reaction Nearly 10% patients suffer from mild gastrointestional disturdance, insomnia、headache and rash . More serious adverse effects are rare but include increased aminotransferase , alkaline phosphatase activity and myositis (rhabdomyolysis横纹肌溶解 ), creatine kinase肌酸激酶 activity. Bile acid-binding resins cholestyramine考来烯胺 Action and mechanism: Large polymeric anionic exchange resin , insoluble in water Bind bile acids in the intestinal lumen and prevent their reabsorption. Results: 1) Increase bile acids loss, increase conversion of cholesterol to bile acid in hepatocytes; 2) increase synthesis of cholesterol and LDL receptors in hepatocytes; 3) decrease serum LDL and cholesterol levels Uses: hyperchlolesterolemia (Ⅱ type). Side effects and drug interactio