第四章循环系统药物CirculatorySystemA.pptx

hyperlipidemia
Hypercholesterolemia ( LDL)>240mg/dl, Hypertriglyceridemia( VLDL)>140mg/dl
Strongly associated with atherosclerotic (动脉粥样硬化) lesions and coronary(冠状 动脉) heart disease, ---50% CHD related cigarette smoking, physical inactivity and obesity.
来自百度文库
Classified by structure
The treatment of Hypercholesterolemia 1, Bile acid sequestrants（胆汁酸结合树脂） 2, HMG CoA reductase inhibitors（ HMG CoA
还原酶抑制剂）
The treatment of Hypertriglyceridemia 3, Fibrates（苯氧酸类） 586 4, Niacin（烟酸）
Trade Manufacturer name
Lipitor
Pfizer
Zocor
Merck
Pravacol BMS
Lescol
Lopid Baycol Tricor
1, Bile Acid Sequestrants
胆汁酸结合树脂
Cholestyramine(考来烯胺), 1960s Colestipol(考来替泊) , 1977
Discontinuance of Mevastatin
Pre-clinical trail: Reports of altered intestinal morphology
四亚乙基戊胺
587
考来烯胺 考来替泊
Physicochemical Properties
Large, Water –insoluble resins, MW>1,000,000
Cholestyramine (考来烯胺), 16~24grams/D , a powder( a slurry)
Colestipol (考来替泊), 530 grams/D, granules(粒剂) and tablet
H3C HO
C OOO
SCoA
H3C HO
C OOOH
SCoA
H3C HO
C OOO
H
H3C HO
C OOOH
Mevalonic acid
HMG-CoA : 3-hydroxy-3-methylglutary CoA
588 HMG-CoA Reductase HMG-CoA Reductase Inhibitor
Bind bile acid and increase their fecal(粪便的) elimination
Anion-exchange resin
Bile acid sequestrants
Quaternary Ammonium 1973
Secondary Tertiary Amines 1977
Excreted in the feces as an insoluble complex with bile acids
Indications and adverse effects
Hypercholesterolemia : 50% reduction of plasma LDL levels
Historical Overview
1976， Endo and Kuroda, Mevastatin （美伐他丁, Compatin）from Penicillium,
affinity for the enzyme 10,000 times grater than that of HMG CoA
C27 steroid
HMG CoA reductase inhibitors
3-hydroxy-3-methylglutaryl CoA
reductase HMG-CoA reductase , A primary control
site HMG-CoA还原酶抑制剂
HMG-CoA Reductase
Chapter 7
Antihyperlipoproteinemics
降血脂药
lipoprotein
Cholesterol and Cholesterol ester 胆固醇 triglycerides, 甘油三脂 Phospholipids, 磷脂
Cholesterol: cell membranes, androgens, estrogens and progesterone
lipoprotein
CM(乳麋微粒)： Chylomicrons VLDL(极低密度脂蛋白)：very low-
density lipoprotein LDL(低密度脂蛋白): low-density
lipoprotein HDL(高密度脂蛋白): high-density
lipoprotein
One of the safest drugs to use Gastrointestinal symptoms Constipation
（便秘）, bloating(腹胀)， abdominal discomfort
2, HMG CoA reductase inhibitors
Cholesterol
Antihyperlipidemic drugs in the top 200
Rank in 2001 2 21 47 68
115 157 176
Generic name
Astorvastatin Simvastatin Pravastatin Fluvastatin
sodium Gemfibrozil Cerivastatin fenofibrate
Tablet should not to be chewed, crushed, cut
Metabolism
Not orally absorbed and metabolized by gastrointestinal enzymes: onset of action 1~2 days, 1 month.