Cytotoxic agents cyclophosphamide

Cytotoxic agents which are used both for the treatment of cancer as for their immunosuppressive activity include cyclophosphamide, methotrexate, chlorambucil, vincristine, vinblastine and dactinomycin. 

The approach to PNET is similar to that described for osteosarcomas, although the chosen cytotoxic agents are different and radiotherapy plays a more important role. Treatment should be started with chemotherapy, usually comprising a combination of agents such as doxorubicin, VP-16, ifosfamide or cyclophosphamide, actinomycin-D and vincristine. After an optimal local response has been obtained, either surgery or local radiotherapy is applied depending on the site of the disease and the applicability of the technique. Sometimes a combination of both is applied. After optimal local treatment. 

Azathioprine also has applications in certain disorders with autoimmune components, most commonly rheumatoid arthritis. It is as effective as cyclophosphamide in the treatment of Wegener s granulomatosis. It has largely been replaced by cyclosporine in immunosuppressive therapy. Relative to other cytotoxic agents, the better oral absorption of azathioprine is the reason for its more widespread clinical use. 

Azathioprine, cyclophosphamide, methotrexate, leflunomide Lymphocyte-specific cytotoxic agents Mycophenolate mofetil... 

The treatment of collagen disease is based on immunosuppressive therapies. Immunosuppressive agents, such as corticosteroids, are widely used. In addition, cytotoxic agents (azathioprine, cyclophosphamide, and methotrexate) have also been administered. 

Cytotoxic agents destroy immimologically competent cells. Azathioprine, a prodrug for the purine antagonist mercaptopurine, is used in autoimmune disease because it provides enhanced immunosuppressive activity. Cyclophosphamide is a second choice. Bone marrow is depressed as is to be expected. 

The immunosuppressive effect of cytotoxic agents, with or without the concurrent use of steroids, can result in serious infections, which are the primary cause of death in patients with minimal-change nephropathy. Other toxicities associated with cyclophosphamide include gonadal fibrosis, which results in sterility, hemorrhagic cystitis, alopecia, and a potential to develop malignancy in those on long-term treatment. Patients on chronic steroid therapy often develop growth retardation, osteoporosis, obesity, and cataracts. ... 

Cytotoxic agents, when used in conjunction with corticosteroids, are effective in increasing the remission rate of nephrotic syndrome and reducing the frequency of ESKD at 10 years. Ponticelli and colleagues devised such a regimen by combining intravenous methyl-prednisolone (1 g) for 3 days followed by oral methylprednisolone (0.4 mg/kg) for the subsequent 27 days of months 1, 3, and 5. Oral chlorambucil (0.2 mg/kg) is to be given daily in months 2, 4, and 6. They also substituted cyclophosphamide (2.5 mg/kg per day) for chlorambucil, which resulted in similar rates of proteinuria remission and relapse, but with fewer serious side effects in those who received cyclophosphamide. ... 

The anticancer drugs cisplatin cyclophosphamide - and ifosfamide alter the profile of P450 enzyme expression in liver and perhaps other tissues, at least in part due to the hormonal perturbations that these cytotoxic agents induce. Treatment of adult male rats with a single dose of cisplatin depletes serum androgen, and this effect persists for up to 28 days after drug administration . Serum androgen depletion by cisplatin is associated with a feminization of hepatic liver enzyme expression. Thus, cisplatin-treated male rats have elevated levels of the female-predominant... 

Allopurinol inhibits the enzymatic inactivation of mercaptopurine and its derivative azathio-prine by xanthine oxidase. Thus, when allopurinol is used concomitantly with oral mercaptopurine or azathioprine, dosage of the antineoplastic agent must be reduced by 25-33% (see Chapters 38 and 51). This is of importance when treating gout in the transplant recipient. The risk of bone marrow suppression also is increased when allopurinol is administered with cytotoxic agents that are not metabolized by xanthine oxidase, particularly cyclophosphamide. 

ALKYLATING AGENTS Cyclophosphamide (cytoxan, neosar) is an effective cytotoxic and immunosuppressive agent. 

Many cancer therapies use non-S-phase-specific cytotoxic agents and the question arises whether a cell-cycle inhibitor like rhMIP-la/BB-10010 can protect normal cell from these agents. This question has been addressed using the clinically relevant non-S-phase-specific cytotoxic drug cyclophosphamide in murine chemotherapy models, which are typically less myeloablative than those described above (38). In these studies BB-10010 was administered continuously by osmotic minipump during days 0-7 at 40 pg... 

The clinical course of chronic ILD is almost always slowly progressive, with stabilization over years (293,315). There is a paucity of data on the efficacy of corticosteroids, and immunosuppressive or cytotoxic agents. In one series, 9 of 14 patients responded to four weeks or more of corticosteroid therapy, but follow-up was short (293). The choice of immunosuppressive agent is uncertain, with cyclophosphamide often used in severe or progressive disease. 

Chemotherapeutic agents are grouped by cytotoxic mechanism. The alkylating agents, such as cyclophosphamide [50-18-0] and melphalan [148-82-3] interfere with normal cellular activity by alkylation deoxyribonucleic acid (DNA). Antimetabohtes, interfering with complex metaboHc pathways in the cell, include methotrexate [59-05-2] 5-fluorouracil [51-21-8] and cytosine arabinoside hydrochloride [69-74-9]. Antibiotics such as bleomycin [11056-06-7] and doxombicin [23214-92-8] h.a.ve been used, as have the plant alkaloids vincristine [57-22-7] and vinblastine [865-21-4]. 

I 10. The answer is a. (Hardman, p 1302J Cyclophosphamide is classified as a poly functional alkylating drug that transfers its alkyl groups to cellular components. The cytotoxic effect of this agent is directly associated with the alkylation of components of DNA. Methotrexate and 5-FU are classified as anti metabolites that block intermediary metabolism to inhibit cell proliferation. Tamoxifen is an antiestrogen compound. Doxorubicin is classified as an antibiotic chemotherapeutic agent. 

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