Hormonal Phenobarbital

Miscellaneous Pharmaceutical Processes. Solvent extraction is used for the preparation of many products that ate either isolated from naturally occurring materials or purified during synthesis. Among these are sulfa dmgs, methaqualone [72-44-6] phenobarbital [50-06-6] antihistamines, cortisone [53-06-5] estrogens and other hormones (qv), and reserpine [50-55-5] and alkaloids (qv). Common solvents for these appHcations are chloroform, isoamyl alcohol, diethyl ether, and methylene chloride. Distribution coefficient data for dmg species are important for the design of solvent extraction procedures. These can be determined with a laboratory continuous extraction system (AKUEVE) (244). 

Drug-induced osteoporosis may result from systemic corticosteroids (prednisone doses greater than 7.5 mg/day), thyroid hormone replacement, some antiepileptic drugs (e.g., phenytoin, phenobarbital), depot medroxyprogesterone acetate, and other agents. 

To understand the MOA by which the thyroid tumors are produced, the effect of pyrethrins on rat thyroid gland, thyroid hormone levels, and hepatic thyroxine UDP-glucuronosyltransferase activity was also investigated [128]. The treatment of male rats with 8,000 ppm pyrethrins, female rats with 3,000 and 8,000 ppm pyrethrins, and both sexes with phenobarbital resulted in increased thyroid gland... 

Pharmaceutical Processes. The pharmaceutical industry1 is a principal user of extraction because many pharmaceutical intermediates and products arc heat-sensitive and cannot be processed by methods such as distillation. A useful broad review can be found in Ihe literature. Extraction is used in the production of antibiotics, vitamins, sulfa drugs, meihaqualune. phenobarbital. antihistamines, cortisone, estrogens and other hormones (qv). and reserpine and alkaloids. 

Normal growth hormone concentrations are found in car-bamazepine-treated patients (94). Growth hormone secretion in response to levodopa stimulation was not affected by carbamazepine or phenobarbital, whereas phenytoin and anticonvulsant polytherapy caused an increase in growth hormone concentration, and valproate a fall at varying times after the administration of levodopa (95). Pubertal growth arrest has been described in a 12-year-old girl who had taken valproate for 18 months (SED-13,152). 

Carbamazepine, phenobarbital, phenytoin, and anticonvulsant polytherapy increased both basal and stimulated concentrations of prolactin, whereas valproate did not (95). However, in other studies, prolactin was unchanged (94). In boys, phenobarbital lowered baseline LH and FSH concentrations and their response to releasing hormone baseline prolactin concentration was raised in comparison with healthy children, and the response of prolactin concentrations to stimulation was impaired (99). 

Increased P450 synthesis requires enhanced transcription and translation. A cytoplasmic receptor (termed AhR) for polycyclic aromatic hydrocarbons (eg, benzo[a]pyrene, dioxin) has been identified, and the translocation of the inducer-receptor complex into the nucleus and subsequent activation of regulatory elements of genes have been documented. A pregnane X receptor (PXR), a member of the steroid-retinoid-thyroid hormone receptor family, has recently been shown to mediate CYP3 A induction by various chemicals (dexamethasone, rifampin) in the liver and intestinal mucosa. A similar receptor, the constitutive androstane receptor (CAR) has been identified for the phenobarbital class of inducers (Sueyoshi, 2001 Willson, 2002). 

Metabolites of PCBs also exert biological effects. The Ah-receptor mediated responses, however, are probably caused by the parent compounds only. The effects of hydroxylated PCBs include inhibition of cytochrome P450-dependent enzyme activities and competitive interference with thyroid hormone and vitamin A metabolism.89,90 Methylsulfonyl-PCBs have been shown to inhibit aryl hydrocarbon hydroxylase activity91 and to elicit phenobarbital-type toxicity and may in fact be responsible for the observed effect presumed to be caused by the parent compound.92... 

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