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66 Cards in this Set
- Front
- Back
What are the 3 classes of alkylating agents?
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1. nitrogen mustards
2. alkyl sulfonates 3. nitrosureas |
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What is MoA of alkylating agents?
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attach an alkyl group to DNA - causes fragmentation, mutation, and cross linking
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What are the nitrogen mustards? (6)
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1. cyclophosphamide
2. ifosphamide 3. chlorambucil 4. melphalan 5. mechlorethamine 6. bendamustine |
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What are the typical alkylating agent toxicities?
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myelosuppression, N/V/D, anorexia, mucositis, alopecia, infertility, risk of secondary leukemia
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Which two alkylating agents require liver metabolism to their active form and cause hemorrhagic cystitis?
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cyclophosphamide, ifosfamide
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What is a unique toxicity of cyclophosphamide/ifosfamide?
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bladder irritation
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When is mechlorethamine used?
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salvage therapy of HD
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When is chlorambucil used?
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older patients with CLL, rarely in lymphomas
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When is cyclophosphamide used?
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HD/NHL, acute and chronic leukemias, mycosis fungoides, multiple myeloma
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When is melphalan used?
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multiple myeloma
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When is bendamustine used?
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recently approved in CLL and NHL
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What is an example of an Alkyl sulfonate?
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Busulfan
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When is busulfan used?
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CML and myeloproliferative disorders
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What is busulfans unusual AE?
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Pulmonary fibrosis (can be years after exposure)
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What are two examples of nitrosoureas?
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carmustine, lomustine
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When are the nitrosoureas used?
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brain tumors (good CNS penetration)
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What is an example of an atypical alkylating agent?
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procarbazine
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When is procarbazine used?
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HD and NHL
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How do the platinum analogs work?
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cross link DNA preventing replication
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What are the platinum analogs? (3)
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1. cisplatin
2. carboplatin 3. oxaliplatin |
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What are the platinum analog AEs? (5)
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1. neuropathy
2. myelosupression 3. NVD 4 hypersensitivity 5 extreme cold sensitity |
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What are the antimetabolites?
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cytotoxic agents from natural sources resembling vitamins, nucleosides, or amino acids
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Which 2 antimetabolites are folic acid analogs?
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methetrexate and pemetrexed
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How does methotrexate work?
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competitively inhibits DHFR which inhibits thymidine sythesis, purines, and AA synthesis
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How is pemetrexed an improvement on methotrexate?
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multi-targeted antifolate, when given with B12 and folate has less toxicity and equal efficacy with methotrexate
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What are the purine inhibitors?
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6-mercaptopurine
6-thioguanine |
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How do 6-mercaptopurine and 6-thioguanine work?
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feedback inhibition stops purine biosynthesis, inhibit DNA and RNA synthesis, block chromosomal replication
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What happens if you give 6-mercaptopurine with allopurinol?
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blocks metabolism, toxic build up of 6-MP
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What are the purine analogues?
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fludarabine and cladribine
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How do fludarabine and cladribine work?
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inhibit DNA and RNA synthesis, inhibit adenosine deaminase
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Why are fludarabine and cladribine particularly effective in lymphoid cells?
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inhibition of adenosine deaminase leads to toxic accumulation of adenosine in lymphoid cells
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What is the major AE of fludarabine and cladribine?
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major immunosuppression with risk of PCP and fungal infections, viral reactivation
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How can you help limit toxicity of methotrexate?
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give leucovorin (folinic acid) 24 hours after administration
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What are the pyrimidines? (5)
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1. 5-fluorauracil
2. capecitabine 3. gemcitabine 4. cytarabine 5. 5-azacitidine |
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How does 5-fluorouracil work?
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binds to thymidylate synthase, can't make thymidine from uracil, can't make DNA
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What happens if you give leucovorin with 5-FU?
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stabilizes drug and increases toxicity
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What is the PO form of 5-FU?
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capecitabine
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What is gemcitabine and analog of?
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cytidine
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How does 5-azacitidine, decitabine work?
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incorporated into DNA causing termination, also causes demethylation of gene promotor sequences, can rescue tumor supressor genes
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How does gemcitabine work?
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incorporates into DNA and causes "masked chain termination"
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How does cytarabine work?
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incorporates into DNA and causes chain termination
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What is a major concern with cytarabine?
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neurotoxicity
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What does dactinomycin do?
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intercalates in double strand DNA preventing replication and transcription
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How does Bleomycin work?
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complexes with free radicals and binds to and breaks DNA
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What is a serious AE with bleomycin?
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pulmonary inflammation and fibrosis (low bleomycin hydrolase, high O2)
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What are two anthracyclins?
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doxorubicin, daunorubicin
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How do anthracyclines work?
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inhibit topoisomerase II, intercalate in DNA, generate free radicals
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What is the worrying AE of the anthracyclines?
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cardiac toxicity (based on cumulative dose)
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What is etoposide (VP-16)?
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a topoisomerase II inhibitor that causes DNA damage
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Name two vinca alkaloids
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vincristine, vinblastine
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How do the vinca alkaloids work?
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bind to microtubules and block mitotic spindle formation, block mitosis
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What is the major AE of the vinca alkaloids?
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peripheral neuropathy
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Name two taxanes
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paclitaxel, docetaxel
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How do the taxanes work?
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bind to tubulin and cause M phase mitotic arrest
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What are the major AEs of the taxanes? (2)
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1. acute allergic reactions to solvents
2. neuropathies |
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How does hydroxyurea work?
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inhibits ribonucleotide reductase, depletes DNA building blocks
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When is hydroxyurea used?
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to bring down blood counts in leukemias, CML, sickle cell
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What drug is an improvement on thalidomide?
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lenalidomide
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When are thalidomide and lenalidomide used?
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multiple myeloma
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What are two SERMS?
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tamoxifen, raloxifene
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How do the SERMS work?
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bind to ERs, block normal binding and activation by estrogen
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What are some side effects of SERMS?
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hot flashes, vaginal dryness, osteoprotective, increase endometrial cancer, increase clots
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What does fulvestrant do?
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not only blocks ERs (like SERMS) but also degrades ERs by preventing dimerization
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Name 2 aromatase inhibitors?
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anastrazole, letrozole
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What do anastrazole and letrozole do?
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block conversion of androgens to estrogen lowering estrogen levels in post-menopausal women
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Name two long acting LHRH analogs?
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goserelin, leuprolide
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