Methotrexate Dexamethasone

Baker K, Sengupta D, Salazar-Jimenez G, Cornish VW. An optimized dexamethasone-methotrexate yeast 3-hybrid system for high-throughput screening of small molecule-protein interactions. 

H. Lin, W. Abida, R. Sauer, W.V. Cornish, Dexamethasone-methotrexate an efficient chemical inducer of protein dimerization in vivo, J. Am. Chem. Soc. 2000, 122, 4247-4248. 

P-gp (ABCB1) Verapamil, digoxin, mitoxantrone, vinblastine, doxorubicin, losartan, talinolol, cortisol, dexamethasone, colchicine, loperamide, domperidone, indinavir, erythromycin, tetracycline, itraconazole, cyclosporine, methotrexate, amitryptyline, phenobarbital, morphine, cimetidine, and others... 

There are certain histologic subtypes of diffuse, aggressive NHL that respond less well to treatment with conventional regimens such as CHOP. Burkitt s lymphoma, lymphoblastic lymphoma, mantel cell lymphoma, and primary CNS lymphoma are examples of disease that benefit from more intensive therapy. Regimens such as hyper-CVAD, which alternate cycles of hyperfractionated cyclophosphamide, doxorubicin, vincristine, and dexamethasone with high-dose cytarabine and methotrexate, often are substituted for CHOP. Intrathecal therapy with methotrexate is indicated with documented CNS infiltration of tumor or involvement of the sinuses. The recent appreciation of the etiology of Helicobacter pylori in the etiology of peptic ulcer disease and the association between colonization and mucosal-associated lymphoma (MALT) has spurred... 

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. 

C, cytarabine ASP, asparaginase CALCB, Cancer and Leukemia Croup B CNS, central nervous system CTX, cyclophosphamide DEX, dexamethasone DNR, daunorubicin DOX, doxorubicin IT, intrathecal captopurine MTX, methotrexate PRED, prednisone TG, thioguanine VCR, vincristine. 

Methotrexate 20 mg/m2 per dose orally at bedtime weekly Mercaptopurine 75 mg/m2 per dose orally daily on days 0-49 Vincristine 1.5 mg/m2 per dose (max 2 mg) IV on days 0 and 28 Dexamethasone 6 mg/m2 per day orally on days 0-4 and 28-32 Delayed intensification (1 or 2 cycles) (2 months)... 

The first-line agents in the treatment of rheumatoid arthritis are non-steroidal anti-inflammatory drugs such as diclofenac. Diclofenac and indometacin, another NSAID, tend to have similar activity hov/ever, indometacin has a higher incidence of side-effects and therefore diclofenac is more appropriate for initial treatment. Sodium aurothiomalate is classified as a disease-modifying antirheumatic drug and is used as a second-line treatment in rheumatoid arthritis, but has been superseded by methotrexate, administered v/eekly. Paracetamol is often indicated in the management of osteoarthritis. Local intra-articular injections of dexamethasone may be administered for the relief of soft-tissue inflammatory conditions. 

Fig. 1. Outline of treatment strategy applied in the ALL-Berlin-Frankfurt-Munster (BFM) 95 study (1995-2000). Patients were assigned to standard-risk (SR), intermediate-risk (MR) and high-risk (HR) subgroups. Elements containing 6-mercaptopurine (6-MP) or 6-thioguanine (6-TG) are indicated in grey. Abbreviations PRED-GR, prednisone good response PRED-PR, prednisone poor response DEXA, dexamethasone VCR, vincristine DNR, daunorubicin HD-MTX, high-dose methotrexate LD-ARA-C, low-dose cytarabine SCT, stem cell transplantation.

Fleck C, Hilger R, Jurkutat S, et al. Ex vivo stimulation of renal transport of the cytostatic drugs methotrexate, cisplatin, topotecan (Hycamtin) and raltitrexed (Tomudex) by dexamethasone, T3 and EGF in intact human and rat kidney tissue and in human renal cell carcinoma. Urol Res 2002 30 256-262. 

Bleomycin Bleomycin is incompatible and loses its potency if it is administered with solutions of benzylpenicillin sodium, carbenicillin, cephazolin or cephalothin sodium, hydrocortisone sodium succinate, mitomycin, methotrexate, nafcillin sodium, aminophylline, ascorbic acid, terbutaline, divalent and trivalent cations (especially copper), compounds containing sulfhydryl groups, and precipitation by hydrophobic anions, essential amino acids, riboflavine, dexamethasone, and frusemide. 

Plasmapheresis is effecdve in patients with severe neuropsychiatric SLE refractory to conventional treatment. Intrathecal methotrexate and dexamethasone is also beneficial to those patients (Dong et al., 2001 Baca et al., 1999). Positive results of a phase I/n trial of autologous hematopoietic stem cell transplantadon (AHSCT) at Northw estem University in Chicago, UL has led to a phase HI ASCT dial. As with other similar dials involving autoimmune disease, the ASCT dial is designed to include standard of care PV pulse cyclophosphamide (Burt et al., 2003b). 

Dong Y, Zhang X, Tang F, Tian X, Zhao Y, Zhang F (2001) Intrathecal injection with methotrexate plus dexamethasone in the treatment of central nervous system involvement in systemic lupus erythematosus. Chin Med J (Engl) 114 764—766. 

Dexamethasone increased the hepatotoxicity of methotrexate in 57 children with brain tumors (137). The hepatotoxicity was not related to differences in serum concentrations and was independent of bone marrow toxicity or mucositis. 

Clinically important, potentially hazardous interactions with acenocoumarol, anagrelide, anticoagulants, bismuth, boswellia, calcium hydroxylapatite, capsicum, cholestyramine, desvenlafaxine, devil s claw, dexamethasone, dexibuprofen, dicumarol, etodolac, evening primrose, flunisolide, ginkgo biloba, ginseng, heparin, ibuprofen, indomethacin, ketoprofen, ketorolac, lumiracoxib, methotrexate, methylprednisolone, nilutamide, NSAIDs, phellodendron, prednisone, resveratrol, reteplase, rivaroxaban, sermorelin, sulfites, tirofiban, triamcinolone, urokinase, valdecoxib, valproic acid, verapamil, warfarin... 

MACOP-B methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin MALT mucosa-associated lymphoid tissue M-BACOD methotrexate, bleomycin, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), and dexamethasone MCL mantle cell lymphoma... 

HLA human leukocyte antigen HSCT hematopoietic stem cell transplantation hyper-CVAD high-dose methotrexate and cytarabine alternating with fractionated cyclophosphamide plus vincristine, doxorubicin, and dexamethasone IBMTR International Bone Marrow Transplant Registry IL-2 interleukin-2 MDS myelodysplastic syndrome MLL mixed lineage leukemia MUD matched unrelated donor NCCN National Comprehensive Cancer Network NST nonmyeloablative stem cell transplant OS overall survival Ph+ Philadelphia chromosome PML promyelocytic leukemia (gene)... 

A = Adults C = children MTX = methotrexate MP cyclophosphamide Dexa = dexamethasone. 

In view of successful animal experiments (20 see also Chapter 14), a sustained-release dexamethasone device was implanted in one eye of a patient with bilateral severe uveitis associated with multiple sclerosis (20,21). The patient had previously undergone pars plana lensectomy and vitrectomy in the right eye for decreased vision associated with cataract. Despite chronic topical corticosteroids, the patient had persistent bilateral low-grade inflammation and recurrent severe bilateral iridocyclitis. Best corrected visual acuity was 20/400 in both eyes. Systemic corticosteroids and methotrexate controlled the intraocular inflammation but the patient was intolerant of these medications because of systemic side effects. The nondegradable dexamethasone device was inserted into the patient s left eye. 

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