Nitrogen mustards treatment

There is some evidence that nitrogen mustard treatment in humans may result in decreased ferlilily. 

Uses The nitrogen mustards are used clinically in the treatment of certain neoplasms (14). They have been used in treatment of Hodgkin s disease, lymphosarcoma, and leukemia (see Chemotherapeutics, anticancer). 

Nitrogen mustard is clinically used for the treatment of lymphomas and some forms of lung cancer. The major indication for mechlorethamine is Hodgkin s disease as a part of the MOPP regimen (mechlorethamine + vincristine (oncovin) + procarbazine + prednisone). The usual dose consists of 6 mg/m2 on days 1 and 8. This drug has pronounced hematological toxicity (myelo-suppression). 

Chemotherapy of cancer started in the early 1940s when nitrogen mustard was administered to patients with lymphoma. Since then, numerous agents have been developed for the treatment of different cancers. 

Very reactive nitrogen mustards and aziridine-containing molecules are usually too toxic for general therapeutic use, but find use in neoplastic disease. Benzodepa (182) is such an agent. Treatment of ethyl carbamate with phosphorous pentachloride leads to cyanate 180 which readily adds benzyl alcohol to produce carbamate 181. Displacement of the active... 

A lysogenic culture can be treated so that most or all of the cells produce virus and lyse. Such treatment, called induction, usually involves the use of agents such as ultraviolet radiation, nitrogen mustards, or X rays, known to damage DNA and activate the SOS system. However, not all prophages are inducible in some temperate viruses, prophage expression occurs only by natural events. 

It is sometimes possible to eliminate the lysogenic virus (to cure the strain) by heavy irradiation or treatment with nitrogen mustards. Among the few survivors may be some cells that have been cured. Presumably the treatment causes the prophage to detach from the host chromosome and be lost during subsequent cell growth. Such a cured strain is no longer immune to the virus and can serve as a suitable host for study of virus replication. 

NITROGEN MUSTARD AND MITOMYCIN C Treatment 1. Mix 4 cc 10% sodium thiosulfate with 6 cc of sterile H20 -inject 2 cc into site for each mg of drug extavasated... 

Caution There is no antidote for nitrogen mustard toxicity decontamination of all potentially exposed areas within minutes after exposure is the only effective method to decrease tissue damage. Other than that, treatment is mainly supportive. 

Mechlorethamine (nitrogen mustard Mustargen), a derivative of the war gas sulfur mustard, is considered to be the first modern anticancer drug. In the early 1940s it was discovered to be effective in the treatment of human lymphomas. 

The major indication for mechlorethamine is Hodgkin s disease the drug is given in the MOPP regimen (mechlorethamine, vincristine, procarbazine, prednisone see Chapter 55). Other less reactive nitrogen mustards are now preferred for the treatment of non-Hodgkin s lymphomas, leukemias, and various solid tumors. 

Thiotepa has antitumor activity against ovarian and breast cancers and lymphomas. However, it has been largely supplanted by cyclophosphamide and other nitrogen mustards for treatment of these diseases. It is used by direct instillation into the bladder for multifocal local bladder carcinoma. 

The three principal classes of cytotoxic agents used in the treatment of cancer all contain carcinogens, for example, Melphalen, a nitrogen mustard, adriamycin, an antitumor antibiotic, and methotrexate, an antimetabolite. Diethylstilbestrol (DES), a drug formerly widely used, has been associated with cancer of the cervix and vagina in the offspring of treated women. 

The management of cancer includes treatment with alkylating agents (nitrogen mustards and alkyl sulfonates), antimetabolites (methotrexate and purine analogs), natural products (vinca alkaloids and antibiotics), miscellaneous compounds (hydroxyurea, procarbazine, and cis-platinum), hormones (estrogens and corticosteroids), and radioactive isotopes (see Chapter 62). 

Chlorambucil (Leukeran) is the least toxic nitrogen mustard, and is used as the drug of choice in the treatment of chronic lymphocytic leukemia. It is absorbed orally, is slow in its onset of action, and may cause bone marrow depression. 

Cyclophosphamide (6.31) is a nitrogen mustard used for cancer treatment (Scheme 6.9). In the body, cyclophosphamide is oxidized to aminal 6.32. Compound 6.32 opens and loses acrolein to form phosphoramide mustard (6.33). Structure 6.33 is a strong bis-electrophile and reacts readily with nucleophiles. In DNA, the nucleophile tends to be N7 of guanine, which is oriented outward into the major groove (Figure 6.6). By reacting twice, 6.33 crosslinks DNA either within the same strand (intrastrand) or across the double helix (interstrand).16... 

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