Phenobarbital for

To understand the MOA for liver tumor formation, the hepatic effects of pyrethrins have been investigated [130]. Male Sprague-Dawley CD rats were fed diets containing 0 (control) and 8,000 ppm pyrethrins and female rats diets containing 0, 100, 3,000, and 8,000 ppm pyrethrins for periods of 7, 14, and 42 days, and 42 days followed by 42 days of reversal. Rats were also fed diets containing 1,200-1,558 ppm sodium phenobarbital for 7 and 14 days as a positive control. The treatment of male rats with 8,000 ppm pyrethrins, female rats with... 

Glucuronide synthesis is the rate-determining step in hepatic bilirubin metabolism. Drugs such as phenobarbital, for example, can induce both conjugate formation and the transport process. 

TABLE 5-9. Neuroleptics versus phenobarbital for schizophrenia acute treatment... 

By 1912, von Mering and Fischer developed and commercially introduced a new barbiturate compound for sleep and anxiety called phenobarbital or Luminal. However, this medication quickly found its place as treatment for a very different medical condition, epilepsy, which is a condition of periodic, unprovoked convulsions or seizures. The main goal of epilepsy treatment is to decrease the frequency of seizures. Alfred Hauptmann discovered the anti-epileptic properties of phenobarbital accidentally. A 1912 report by Hauptmann described epileptic patients who were given phenobarbital for sedation and incidentally had fewer seizures. Seizures are caused by an abnormal impulse in the brain, which spreads and sends inappropriate message to the body. These messages result in... 

Figure 1 Immunoblot analysis of CYP3A (A) and CYP2B (B) protein in rat hepatocytes cultured on Matrigel and collagen. Cells were incubated in the presence of 10-p.M dex-amethasone or 50-p.M phenobarbital for 48 hours. Source From Ref. 12.

Sedative-hypnotic drugs and anxiolytic drugs are CNS depressants that are used medically to reduce anxiety and/or induce sleep. They may also be used as anticonvulsants. Phenobarbital, for example, is often the maintenance drug of choice for seizure-prone individuals. In general, the sedative-hypnotic family of drugs includes alcohol, barbiturates, benzodiazepines, and such barbiturate-like drugs as chloral hydrate, glutethi-mide, meprobamate, and methaqualone. 

Pal DK, Das T, Chaudhury G, Johnson AL, Neville BG. Randomised controlled trial to assess acceptability of phenobarbital for childhood epilepsy in rural India. Lancet 1998 351(9095) 19-23. 

Emergency supplies (see Chapter 7) of Schedule 2 and Schedule 3 controlled drugs are not allowed except phenobarbital for the treatment of epilepsy. 

Treatment of immature male rats with phenobarbital for three days increased the 6 ft-, la-, and 16a-hydroxyl ati on of testosterone by liver microsomes to different degrees (36). The 16a-hydroxyl ati on reaction was stimulated several-fold, whereas the 6ft- and 7a-hydroxylations were stimulated to a smaller extent. In contrast to these results, the administration of 3-methylcholanthrene had little or no stimulatory effect on the 6ft- or 16a-hydroxylation of testosterone by liver microsomes but caused a significant increase in the 7 a-hydroxy 1 ati on reaction. 

Crawford TO, Mitchell WG, Fishman LS, Snodgrass SR. Very-high-dose phenobarbital for refractory status epilepticus in children. Neurology 1988 38 1035-1040. 

The use of phenobarbital for acute alcohol withdrawal remains controversial. Despite its time-honored place in therapy, there is a lack of published evidence-based support for its efficacy and safety for acute alcohol withdrawal. 

The treatment of folate deficiency in patients receiving anticonvulsant drugs is not without difiiculties. Chanarin (C3) described an epileptic patient who had developed a megaloblastic anemia due to folate deficiency. Treatment with folic acid apparently precipitated convulsions. Up to this time the patient had been free of seizures while on phenobarbital for 4 years. There have since been a number of reports of treatment with folic acid precipitating seizures in patients with epilepsy (D6, R3, W8). 

Phenobarbital For generalized seizures in pediatric patients. Used less often in adults. Described in tables 3.8A,B. 

A patient with neuroeysticercosis taking phenytoin and phenobarbital for a seizure disorder had no response to praziquantel (four courses in doses of up to 50 mg/kg daily). Praziquantel 50 m g daily and dexamethasone 12 mg daily were started and, after one week, cimetidine 400 mg four times daily was added. The patient s serum praziquantel levels more than doubled with the addition of cimetidine (maximum serum levels raised from 350 to 826 nanograms/mL) and the AUC rose about fourfold, and became similar to that found in control subjects taking praziquantel alone. The patient showed marginal improvement, and continued to slowly improve over the following 4 months. ... 

Another study eonfirmed that this interaction occurred in 20 neonates, but no statistically significant effect was found in 40 infants. Decreased chloramphenicol levels have been described in a single case report of a child who was also being treated with phenytoin and phenobarbital. The serum chloramphenicol levels were 35.1 micrograms/mL prior to the antiepileptics, 19.1 micrograms/mL after 2 days of phenytoin and 13.2 micrograms/mL a month after the addition of phenobarbital. For more information on the interaetion of ehloramphenieol with phenytoin see Phenytoin + Chloramphenieol , p.555. 

In an earlier study, phenobarbital 125 mg daily for 4 days caused only a small reduction in the plasma half-life of quinine in 2 healthy subjects. Information seems to be limited to these studies. The importance of the interactions with either carbamazepine and phenobarbital awaits assessment in a clinically realistic situation (i.e. in patients taking multiple doses) but in the meantime it would seem prudent to monitor the effects of carbamazepine or phenobarbital for evidence of increased effects and possible toxicity if quinine is also taken. 

An HIV-positive man taking phenytoin and phenobarbital for epilepsy had been taking nelflnavir 750 mg three times daily and stavudine 30 mg twice daily for nearly 3 months when he had a tonic-clonic seizure. After starting nelflnavir and stavudine, serum phenytoin levels were found to have dropped from around 10 mg/L to around 5 mgfL Similarly, nelflnavir 1.25 g twice daily for 7 days decreased the AUC of phenytoin by about 30% and the maximum serum level by 21%, in healthy subjects, whereas the nelflnavir levels were not altered. ... 

Recurrent plantar fibromatosis, also known as Ledderhose syndrome, occurred in a patient who had taken phenobarbital for a long time [237 ]. 

Nervous system An infant with drug-resistant epilepsy associated with bilateral Sturge-Weber syndrome became comatose after taking high-dose phenobarbital for a few months and regained consciousness as the serum phenobarbital concentration fell to below 40 [ig/ml. The authors suggested that patients with severe cerebrovascular diseases are more susceptible to the sedative effects of phenobarbital [232 ]. 

A 13-year-old girl with acute intermittent porphyria had several attacks of the disease and developed an acute severe axonal motor neuropathy after taking porphyrinogenic medications, including phenobarbital, for 3 weeks [233 ]. 

Treatment of animals with phenobarbital for 3—6 days increases the liver weight, the liver weight/body weight ratio, microsomal protein content, and the synthesis of microsomal protein. Induction with 3-methylcholanthrene is accompanied by a smaller increase in liver mass and increased synthesis of protein from labelled precursors. In addition to stimulating liva growth in normal animals, enzyme inducers increase the rate of liver regeneration following partial hepatectomy. 

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