Pharm Anticancer Alkylating agents
Terms
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- bladder toxicity, alopecia, lymphocytopenia, immunosuppresion, hemorrhagic cystitis from ACROLEIN, secondary neoplasm,
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CYCLOPHOSPHAMIDE
IFOSFAMIDE
less ADRs with oral Cyclophosphamide, <> Innapropriate secretion of ADH can cause water intoxication - not vesicant, toxicity mainly hemotological
- MELPHALAN
- alkylating agents with renal toxicities
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CYCLOPHOSPHAMIDE
IFOSFAMIDE
BUSULFAN
BCNU (carmustine)
CCNU (lomustine)
CISPLATINUM
CARBOPLATIN - use MESNA (2-mercaptoethanesulfonate) to conjugate toxic metabolites in urine, to wash-out to prevent toxicity
- CYCLOPHOSPHAMIDE
- alkylating agents used in breast cancer
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CYCLOPHOSPHAMIDE
CHLORAMBUCIL
THIOTEPA - works in all patients, even patients deficient in mismatch repair protein when the other two don't work
- OXALIPLATIN
- nitrosoureas
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BCNU (carmustine)
CCNU (lomustine)
methyl-CCNU (semustine)
STREPTOZOCIN - activated by spontaneous breakdown, bifunctional alkylating agents reacting with G, C and A base <> can also modify DNA repair enzymes so inhibit DNA, RNA and protein synthesis
- BCNU (carmustine)
- alkylating agents for testicular cancer
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IFOSFAMIDE
CISPLATINUM - slowest acting nitrogen mustard, must be converted by liver to active metabolite: Phenylacetic Acid Mustard
- CHLORAMBUCIL
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marrow ablative therapy, multiple myeloma, breast, ovary
enter cell via amino acid transporter pump - MELPHALAN
- MECHLORETHAMINE
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Hodgkin (part of MOPP, see Vincristine) and non-Hodgkin, lymphomas and lung carcinoma (infusion for) metastatic carcinoma resulting in effusion
enter cell via amino acid transporter pump - cross BBB, good for brain tumors, also good for Hodgkin and non-Hodgkin, Multiple myeloma and melanoma (also small cell lung for Lomustine)
- nitrosoureas
- local reaction from extravasation = vesicant, can tx with ice compress and thiosulfate
- MECHLORETHAMINE
- triazines
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DACARBAZINE
PROCARBAZINE
TEMOZOLOMIDE
require initial activation by P450, Monofunctional alkylating agent causing depurination and DNA breaks - CML, myeloproliferative d/o such as severe thrombocytosis, polycythemia vera, adjunctive tx in myelofibrosis, used with other drugs like Alopurinol in very high dose to wipe out bone marrow in prep for marrow transplant
- BUSULFAN
- delayed (21 days) leukopenia and thrombocytopenia LUNG, LIVER and KIDNEY TOXICITIES
- BCNU (carmustine)
- lower NAD in beta cell of Langerhans islet
- STREPTOZOCIN
- IV mode
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CYCLOPHOSPHAMIDE (IV or PO)
IFOSFAMIDE
MELPHALAN
MECHLORETHAMINE (IV, intra-peritoneal, pleural, pericardial)
THIOTEPA (IV, intracavity, intravesicular or directly into tumor)
BCNU (carmustine)
STREPTOZOCIN
DACARBAZINE
PROCARBAZINE (PO too)
Platinum analogs - ADRs such as severe nausea, nephrotoxicity, ototoxcity
- CISPLATINUM (Carboplatin less side effects but can cause myelosuppressio and hearing loss)
- are alkylating agents CCS?
- no
- alkylating agents MOA
- substitute alkyl group for active H atom, toxic to rapid growing cells, dose-limiting factor is myelosuppression, reduce women fertility, impair men fertility, chronic use may cause irreversible marrow damage and leukemogenesis, RESISTANCES: 1- decrease permeability of cells, 2-production of Glutathione S-transferase as false target for alkylation, 3-possibly increasing activity of DNA repair systems; TOXICITY: 1-immunosuppression, 2-destruction of GI epithelium and mucositis, possible diarrhea, ADRs: N&V, need Odansetron as antiemetic Tx, amenorrha, impaired spermatogenesis, teratogenesis, alopecia, pulmonary fibrosis, hemorrhagic cystitis (cyclophosphamide and ifosfamide)
- enter cell via amino acid transporter pump
- MELPHALAN
- alkyl sulfonate
- BUSULFAN
- name the group of alkylating agents that cause secondary leukemias
- nitrosoureas
- name the compound that causes secondary lymphomas
- CYCLOPHOSPHAMIDE
- aziridines
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THIOTEPA
HEXAMETHYLMELAMINE - alkylating agent with GI toxicities
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THIOTEPA
MELPHALAN
BUSULFAN - alkylating agent with LIVER toxicity
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BUSULFAN
CARMUSTINE - alkylating agent with lung toxicity
- CARMUSTINE