Induction dexamethasone

The current induction therapy for acute lymphocytic leukemia (ALL) typically consists of vincristine, asparaginase, and a steroid (prednisone or dexamethasone). An anthracycline is added for higher-risk patients. 

RH is admitted to the pediatric oncology service. She is started on allopurinol and intravenous fluids with sodium bicarbonate to prevent tumor lysis syndrome. According to her risk status, she will receive a three-drug induction with vincristine, dexamethasone, and pegylated asparaginase. She also will receive intrathecal (IT) chemotherapy for CNS prophylaxis with methotrexate, cytarabine, and hydrocortisone. 

Villiger PM, Terkeltaub R, Lotz M. Monocyte chemoattractant protein-1 (MCP-1) expression in human articular cartilage. Induction by peptide regulatory factors and differential effects of dexamethasone and retinoic acid. J Clin Invest 1992 90(2) 488 196. 

R4. Rees, D. D., Cellek, S Palmer, R. M. J., and Moncada, S., Dexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects on vascular tone An insight into endotoxin shock. Biochem. Biophys. Res. Commun. 173,541-547 (1990). 

Anti-inflammatory drugs such as pentoxyfUline and dexamethasone inhibited the release of cytokines and thereby the induction of iNOS and the release of NO in the LPS-stimulated... 

Such a medical adrenalectomy is an efficacious treatment for metastatic breast and prostate cancer, since it diminishes the levels of circulating sex hormones. Glucocorticoids are administered concomitantly to suppress enhanced corticotrophin release. Cortisol is preferable to dexamethasone in this situation because aminoglutethimide markedly enhances the hepatic microsomal metabolism of dexamethasone. Hepatic enzyme induction may be responsible for the development of tolerance to the side effects of aminoglutethimide, such as ataxia, lethargy, dizziness, and rashes. 

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). 

Pascussi JM, Drocourt L, Fabre JM, Maurel P, Vilarem MJ (2000a) Dexamethasone induces pregnane X receptor and retinoid X receptor-alpha expression in human hepa-tocytes synergistic increase of CYP3A4 induction by pregnane X receptor activators. Mol Pharmacol 58, 361-372. 

Figure 4 Variability in CYP3A induction in rat hepatocytes from seven different preparations. (A) Represents fold increase in CYP3A protein from dexamethasone-treated cells over nontreated cells. Source From Ref. 12.

Lin JH, Chiba M, Chen IW, et al. Effect of dexamethasone on the intestinal first-pass metabolism of indinavir in rats evidence of cytochrome P-450 3A and P-glycoprotein induction. Drug Metab Dispos 1999 27 1187-1193. 

Lu C, Li AP (2001) Species comparison in P450 induction effects of dexamethasone, omeprazole and rifampin on P450 isoforms 1A and 3A in primary hepatocytes from man, Sprague-Dawley rat, minipig and beagle dog. Chem. Biol. Interact 134 271-281... 

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