tailieunhanh - Human Developmental Toxicants - Part 3

Penicillamine có tiện ích điều trị như là một thuốc giải độc cho đồng và ngộ độc chì và được sử dụng trong điều trị bệnh Wilson và cystinuria và như là một thuốc hỗ trợ trong điều trị viêm khớp dạng thấp. Thuyết cơ giới, penicillamine chelate với một số kim loại nặng để hình thành ổn định, khu phức hợp có thể hòa tan được bài tiết trong nước tiểu. Nó cũng depresses lưu hành IgM yếu tố khớp dạng thấp và tế bào T nhưng không hoạt động của tế bào B, và nó kết hợp với. | 10 Penicillamine Chemical name 3-Mercapto-D-valine CAS 52-67-5 SMILES C C C C S C O O N HO INTRODUCTION Penicillamine has therapeutic utility as an antidote for copper and lead toxicity and is used in the treatment of Wilson s disease and cystinuria and as an adjunct in the treatment of rheumatoid arthritis. Mechanistically penicillamine chelates with a number of heavy metals to form stable soluble complexes that are excreted in urine. It also depresses circulating IgM rheumatoid factor and T cell but not B cell activity and it combines with cystine to form a more soluble compound thus preventing cystine calculi Lacy et al. 2004 . The drug is available by prescription as Cuprimine among other trade names and it carries a pregnancy risk factor of D. The package label states that although normal outcomes have been reported in pregnant women characteristic congenital cutis laxa and associated birth defects have been reported in infants born of mothers who received therapy with penicillamine during pregnancy see below also see PDR 2002 . DEVELOPMENTAL TOXICOLOGY Animals Laboratory animal studies were conducted with the drug in mice hamsters and rats and it is developmentally toxic in all three species. Given by the oral route mice demonstrated cleft palate increased abortion and resorptions and decreased fetal body weight at high doses of g kg when administered 1 or 3 days during organogenesis Myint 1984 . Similar doses in hamsters given on 1 day during organogenesis elicited fetal death decreased fetal body weight malformations of the central nervous system and skeletal defects of the ribs and limbs Wiley and Joneja 1978 . In rats penicillamine given either by oral gavage or fed in the diet during organogenesis or throughout gestation produced malformations palate and skeletal defects reduced fetal body weight and increased resorptions in the range of 360 to 1000 mg kg gavage or and higher diet in several studies Steffek et al. 1972 Yamada et al. 1979 .