Phenobarbital administration

Nakajima T, Okuyama S, Yonekura I, et al. 1985. Effects of ethanol and phenobarbital administration on the metabolism and toxicity of benzene. Chem-Biol Interact 55 23-38. 

Phenobarbital represents the type of enzyme inducer with broad induction effects. After a latency period, production of cytochrome P450, cytochrome P4S0 reductase, and related enzymes is increased. In addition, hver weight, hepatic blood flow, bile flow, and production of hepatic proteins also all increase. This induction apparently increases the P450 isoenzyme mass for which debrisoquin is a substrate, because the hepatic clearance of debrisoquin is increased after phenobarbital administration. This enzyme is referred to as cytochrome P450-2D6 (Gyp 2D6). Phenobarbital induction has little effect on theophylline clearance, suggesting a different isoenzyme for theophylline metabolism. 

Phenobarbital is thought to induce the metabolism of carbamazepine to its epoxide metabolite. Accordingly, after phenobarbital administration, decreased serum carbamazepine concentrations were accompanied by increased epoxide levels. 

Zeidenberg P, Orrenius S, Emster L Increase in levels of glucuronylaling enzymes and associated rise in activities of mitochondrial oxidative enzymes upon phenobarbital administration in the rat. J Cell Biol 32(2) 528-531, 1967. 

Why does the attainment of a steady-state plasma concentration take several weeks with phenobarbital administration ... 

Mezey E, Robles EA. Effects of phenobarbital administration on rates of etiianol clearance and on etiianol-oxidizing enzymes in man. Gastroenterology (1974) 66, 248-53. 

Robinson DS, MacDonald MG. The effect of phenobarbital administration on the control of coagulation achieved during warfarin therapy in man. J Pharmacol Exp Ther (196Q 153, 250-3. 

Lokiec F, Santoni J, WeiU S, Tubiana-Hulin M. Phenobarbital administration does not affect high-dose ifosfamide pharmacokinetics inhumans.z4 tica c erDrM s (199 7, 893-6. 

KandrotasRJ, CranfieldTL, Gal P, Ransom J, Weaver RL. Effect of phenobarbital administration on theophylline clearance in premature neonates, TherDrugMomt( 990) 12,139-43,... 

Betson JR Jr, Alford CD (1961) Stevens-Johnson syndrome secondary to phenobarbital administration in the treatment of toxemia of pre ancy. Obstet Gynecol 18 195 Blomgren SE, Vaughan HJ (1968) The immunogenicity of photo-oxidized DNA and procainamide hydrochloride. Arthritis Rheum 11 470 Braun-Falco O, Bandmann HJ (1970) Das Lyell-Syndrom - Syndrom der verbriihten Haut. Huber, Bern... 

Seifert, J. and Vacha, J. Inhibition of 6-[i C] orotic acid incorporation into the c5dosine moiety of the ribonucleic acid of rat liver cytoplasmic ribosomes after phenobarbital administration. Mol. Pharmacol., 9, 259-265 (1973)... 

VI Vacha, J. and Seifert, J. Turnover of cytidine and uridine components of acid-soluble pool and RNA of cytoplasmic ribosomes after repeated phenobarbital administration. Biochem. Pharmacol., 24, 401-405 (1975)... 

Hamajima, S., Ono, S., Hirano, H., and Obara, K., 1979. Induction of the FAD synthetase system in rat liver by phenobarbital administration. International Journal for Vitamin and Nutrition Research. 49 59-63. 

Phenobarbital administration enhances the metabolism of drugs by microsomal enzymes at four distinct levels (1) by increasing total liver mas% (2) by inaeasing microsomal protein, expressed per gram of liver or per whole liver (3) by increasing the specific activity (enzyme activity/milligram of microsomal protein) of miCTO-somal enzymes (4) by increasing both the amount of NADPH cytochrome c reductase and the amount of cytochrome P-4S0. 

BARBITURATES. The barbiturate phenobarbital (Luminal) is commonly used to treat convulsive disorders. When administering the barbiturates by the intravenous (IV) route, it is important not to exceed a rate of 60 mg/min and to administer the drug within 30 minutes of preparation. The nurse monitors the patient carefully during administration of a barbiturate. The blood pressure and respirations are taken frequently. Resuscitation equipment and artificial ventilation equipment are kept nearby. 

The third protocol is to determine the level of drug use and calculate equivalent doses of phenobarbital (Table 3-5). The patient is stabilized on this dose (divided into administration every 8 hours) for a few days, and then the dose is tapered by 10% daily. Although this method has its proponents, the determination of equivalency is an approximation, drug histories are unreliable, and mixed sedative-hypnotic dependence will complicate the procedure. 

In rabbits under light amytal anesthesia, chlordan has no direcr effect on the blood pressure, but produces a type of respiration having many characteristics in common with Cheyne-Stokes type. The generalized tremors, opisthotonus, tonic and clonic convulsions, produced by chlordan were decreased or abolished and respiration restored to normal by suitable injections of the sodium salts of amytal, phenobarbital, and pentothal. The LD60 of chlordan, which was about 20 mg. per kg. on intravenous administration to intact rabbits, was increased to about 60 mg. per kg. through the antidotal action of the barbiturates. An unidentified chlorine-containing degradation product with acidic properties was recovered from the urine of rabbits treated with chlordan. Approximately one third of its chlorine content was set free on hydrolysis at 100° C. with sodium hydroxide in either absolute alcohol or in water. 

Age-related variations in central nervous system (CNS) neurotransmitter production and receptor sensitivity are the most likely explanations for the pharmacodynamic differences observed between children and adults following administration of psychotropic medications [39a], Children have lower phenobarbital ratios than adults, and the ratio increases with gestational age [40,41]. Conversely, a lower therapeutic range for children has been identified for cyclosporine, phenytoin, and digoxin [42]. 

Date M et al. Differential expression of transforming growth factor-/ and its receptors in hepatocytes and nonparenchy-mal cells of rat liver after CC14 administration. J Hepatol 1998 28 572-581. Frueh FW et al. Extent and character of Phenobarbital-mediated changes in gene expression in the liver. Mol Pharmacol 1997 51 363-369. 

Gut I, Nerudova J, Kopecky J, et al. 1975. Acrylonitrile biotransformation in rats, mice, and Chinese hamsters as influenced by the route of administration and by phenobarbital, SKF 525-A, cysteine, dimercaprol, or thiosulfate. Arch Toxicol 33 151-161. 

Aldous CN, Chetty CS, Desaiah D. 1983. Alterations in tissue distribution of chlordecone (Kepone) in the rat following phenobarbital or SKF-525A administration. J Toxicol Environ Health 11(3) 365-372. 

The gas-uptake data for rats were well described using a single Michaelis-Menten equation to describe metabolism. For the mouse inhalation studies, a simple Michaelis-Menten equation failed to adequately describe the chloroform-metabolizing capacity based on the data collected and model constants. The authors suspected that, following the administration of chloroform (particularly at higher concentrations), destmction of microsomal enzymes and subsequent resynthesis of microsomal enzymes was important in the mouse. This phenomenon has been documented in phenobarbital-induced but not naive rats. To account for this phenomenon, a first-order rate constant for the loss and subsequent regeneration of metabolic capacity was incorporated into the model for mice only. 

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