各论教材Lipid-regulators Agents Used in Hyperlipidemia).pptVIP

Lipid-regulators(Agents Used in Hyperlipidemia);Lipids include:;Lipoproteins include:;;0;The LDL receptor is central to cholesterol homeostasis (1970’s Brown and Goldstein) When LDL binds to its receptor (via recognition of the apoprotein B100) the entire LDL molecule is taken up (engulfed) by the cell in clatherin coated pits endosomes lysosomes;Physiologic Role of Cholesterol Component of all cell membranes Precursor of other steroids Cortisol(糖皮质激素) Progesterone(孕酮) Estrogen(雌激素) Testosterone(睾酮) Bile acids(胆汁酸) Excess cholesterol and/or triglyceride Hyperlipmia (高脂血症) or hyperlipoproteinemia (高脂蛋白血症) Atherosclerosis (动脉粥样硬化) Coronary heart disease (CHD) Xanthomas (黄瘤);LDL is associated with increased heart disease “lousy cholesterol” “bad cholesterol” The major carrier of cholesterol in the blood;Classification of Hyperlipidemias;1.主要降低TC和LDL的药物 他汀类(Statins)：羟甲基戊二酸单酰辅酶A还原酶抑制剂 (HMG-CoA Reductase Inhibitors) – 洛伐他汀(lovastatin)、辛伐他汀(simvastatin)、普伐他汀(pravastatin) 、氟伐他汀(fluvastatin) 、阿伐他汀(atovastatin) 胆汁酸结合树脂 (Bile Acid-Binding Resins, RESINS) – 考来替泊 (Colestipol), 考来烯胺 (cholestyramine) 胆固醇吸收抑制药(Cholesterol absorption inhibitors) –依泽替米贝 (ezetimibe) 2.主要降低TG和VLDL的药物 烟酸 (NICOTINIC ACID, NIACIN)  苯氧酸类(贝特类) FIBRIC ACID DERIVATIVES (FIBRATES) – 氯贝特(clofibrate)、吉非贝齐(gemfibrozil)、苯扎贝特(benzafibrate)、非诺贝特(fenofibrate)、环丙贝特(ciprofibrate) ;Cholesterol Synthesis Pathway;NATURAL PRODUCT HMG CoA REDUCTASE INHIBITORS;NATURAL PRODUCT INHIBITORS ;Statins - Mechanism of Action ;Pharmacologic Therapy: Statins—Dose Response;Most Effective for ↓ LDL Some ↑ HDL and ↓ VLDL Used alone to ↓ LDL Used with resins to ↓ LDL Used with niacin to ↓ LDL, ↓ VLDL, and ↑ HDL Enhanced if taken with food (except for pravastatin – taken without food) Give in the evening (Cholesterol synthesis highest at night);Statins – Benefits;Rash, GI disturbances (dyspepsia(消化不良), cramps, flatulence(肠胀气), constipation(便秘), abdominal pain) Hepatotoxicity Myopathy (肌病)(0.5% of patients) Risk high