Cytochrome P450 system phenobarbital

Acute exposure usually occurs by inhalation. -Hex-ane may be absorbed orally or percutaneously. -Hexane has a vapor density of 2.97 and it is heavier than air. -Hexane is believed to be metabolized through the cytochrome P450 system and phenobarbital pretreatment of liver microsomes induced 2- and 3-hydroxylation of -hexane sixfold. 3,4-Benzpyrene suppresses 2-hydroxylation and stimulates 3-hydroxylation of -hexane. For humans, 2-, 3-hydroxyhexane is responsible for various toxicities. 

Phenobarbital, phenytoin, primidone, and carbamazepine are potent inducers of cytochrome P450 (CYP450), epoxide hydrolase, and uridine diphosphate glucuronosyltransferase enzyme systems. Valproic acid inhibits many hepatic enzyme systems and displaces some drugs from plasma albumin. 

Special attention is needed when new medications are prescribed to CSA-treated patients. CSA is extensively metabolized by the cytochrome P450 hver microsomal enzyme system [2, 3], and consequently drugs that interfere with this pathway can cause important changes in CSA blood levels (Table 3). Compounds inhibiting P450 enzymes, such as ketoconazole, erythromycin, verapamil, and diltiazem increase concentration of parent CSA and may cause acute nephrotoxicity. On the other hand, drugs that increase P450 enzyme activity, such as phenobarbital, carbamazepine and... 

The cytochrome P450 (CYP) system is the group of enzymes of most interest to psychiatrists. These enzymes show considerable genetic variation, and certain isozymes can be induced by specific substrates such as phenobarbital, ethanol, and steroids. They can also be inhibited by various medications that are potent competitive inhibitors of the enzymes (e.g., cimetidine and ketoconazole). 

The inactive metabolites are excreted in the urine. The administration of bicarbonate enhances the urinary excretion of barbiturates that have a pK of 7.4 (phenobarbital and thiopental). This generalization is not true of other barbiturates. The long-term administration of barbiturates activates the cytochrome P450 drug-metabolizing system. 

Drugs, such as phenobarbital, induce enzymes of the drug metabolizing systems of the endoplasmic reticulum that contain cytochrome P450. Because heme is used for synthesis of cytochrome P450, free heme levels will fall and 8-ALA synthase will be induced to increase the rate of heme synthesis. 

It is thought that phenytoin, - carbamazepine and phenobarbital increase the metabolism of the ciclosporin by the liver (hepatic cytochrome P450 oxygenase system) thereby decreasing the serum levels. Oxcarbazepine produced only small reductions in ciclosporin levels, and the effect is probably due to weak induction of the cytochrome P450 isoenzyme CTT3A. Phenytoin also possibly reduces the absorption of the ciclosporin. ... 

The inducing chemicals may have several actions on different enzyme systems (p. 112, Section K). For example, phenobarbital is a relatively poor inducer of ALA synthetase but a good one for cytochrome P450 ... 

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