tailieunhanh - Human Developmental Toxicants - Part 7

Phenobarbital là một barbiturat được sử dụng trong điều trị như là một thuốc chống co giật thuốc an thần, thôi miên, và trong việc quản lý các loại thuốc bổ tổng quát-clonic (lớn mal) và co giật một phần. Nó đã được sử dụng cho những mục đích này trong gần 100 năm. Nó có phân nưa hóa học hoạt động với một loại thuốc chống co giật (và phát triển độc tố), primidone. Thuốc tác động bằng cách thất vọng vỏ cảm giác, giảm động cơ hoạt động, và thay đổi chức năng tiểu não (Lacy et al.,. | Phenobarbital Chemical name 5-Ethyl-5-phenyl-2 4 6 1 3 5H -pyrimidinetrione Alternate names 5-Ethyl-5-phenylbarbituric acid phenobarbitone phenylethylmalonylurea CAS 50-06-6 SMILES C1 c2ccccc2 C NC NC1 O O O CC INTRODUCTION Phenobarbital is a barbiturate used therapeutically as a hypnotic sedative and anticonvulsant in the management of generalized tonic-clonic grand mal and partial seizures. It has been used for these purposes for almost 100 years. It shares the active chemical moiety with another anticonvulsant drug and developmental toxicant primidone. The drug acts by depressing the sensory cortex decreasing motor activity and altering cerebellar function Lacy et al. 2004 . Phenobarbital is obtained by prescription as Luminal and Sulfoton and by many other trade names. It has a pregnancy category of D based on the package label that states barbiturates can cause fetal damage when administered to a pregnant woman. Retrospective case-controlled studies have suggested a connection between the maternal consumption of barbiturates and a higher than expected incidence of fetal abnormalities PDR 2004 . The label goes on to state that fetal blood levels approach maternal blood levels following parenteral administration. DEVELOPMENTAL TOXICOLOGY Animals In animal studies phenobarbital has shown developmental toxicity in mice rats and rabbits by oral and parenteral routes of administration those pertinent to the human condition. In mice the drug induced cleft palate by the oral route in the diet Sullivan and McElhatton 1975 by gavage McElhatton and Sullivan 1977 or via drinking water Finnell et al. 1987 at doses approximating 50 mg kg day and greater over ten or more days during gestation. It also produced cleft palate but no other developmental toxicity in this species mouse subcutaneously at a higher dose of 175 mg kg injected as single doses during gestation interval days 11 to 14 Walker and Patterson 1974 . A second species the rat reacted somewhat differently. When