Continual daily doses of diazepam quickly build to a high concentration in the body (mainly in adipose tissue), far in excess of the actual dose for any given day.Diazepam is stored preferentially in some organs, including the heart. Absorption by any administered route and the risk of accumulation is significantly increased in the neonate, and withdrawal of diazepam during pregnancy and breast feeding is clinically justified.Diazepam undergoes oxidative metabolism by demethylation (CYP 2C9, 2C19, 2B6, 3A4, and 3A5), hydroxylation (CYP 3A4 and 2C19) and glucuronidation in the liver as part of the cytochrome P450 enzyme system. It has several pharmacologically active metabolites. The main active metabolite of diazepam is desmethyldiazepam (also known as nordazepam or nordiazepam). Its other active metabolites include the minor active metabolites temazepam and oxazepam. These metabolites are conjugated with glucuronide, and are excreted primarily in the urine. Because of these active metabolites, the serum values of diazepam alone are not useful in predicting the effects of the drug. Diazepam has a biphasic half-life of about one to three days, and two to seven days for the active metabolite desmethyldiazepam. Most of the drug is metabolised; very little diazepam is excreted unchanged. The elimination half-life of diazepam and also the active metabolite desmethyldiazepam increases significantly in the elderly, which may result in prolonged action, as well as accumulation of the drug during repeated administration. Physical and chemical properties
Diazepam is a 1,4-benzodiazepine. Diazepam occurs as solid white or yellow crystals with a melting point of 131.5 to 134.5 °C.
Human piebaldism has been observed to be associated with a very wide range and varying degrees of endocrine disorders, and is occasionally found together with heterochromia of the irises, congenital deafness, or incomplete gastrointestinal tract development, possibly all with the common cause of premature cutting off of human fetal growth hormone during gestation. Piebaldism is a kind of neurocristopathy, involving defects of various neural crest cell lineages that include melanocytes, but also involving many other tissues derived from the neural crest. Oncogenic factors, including mistranscription, are hypothesized to be related to the degree of phenotypic variation among affected individuals. Genetics
Piebaldism is an autosomal dominant hereditary condition, which tends to produce high rates of inheritance and long chains of generational transmission. All who inherit the gene have at some time in life evidence of piebald hypopigmentation of the hair or skin, most likely both.Piebaldism may be associated with the genes KIT or SNAI2. Diagnosis
Usually diagnosed at birth with the appearance of patches of white skin on the arms, legs, stomach, forehead, and a white lock of hair. History
Early photographers took many photographs of African people with piebaldism as a form of entertainment and exoticism, and George Catlin is believed to have painted several portraits of Native Americans of the Mandan tribe who were affected by piebaldism.Historically, persons with extensive piebaldism have experienced abuse of the sort still suffered in the present by albinos, especially in Africa.