First Aid Cancer Drugs – Flashcards
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MOA of MTX?
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*Folic acid analog* that *inhibits dihydrofolate reductase* leading to a decrease in dTMP which causes a decrease in DNA and protein synthesis
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MTX cancer uses?
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Leukemias, lymphomas, *choriocarcinoma*, sarcoma
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Non neoplastic uses of MTX?
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Abortion, ectopic pregnancy, RA, psoriasis
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Toxicity of MTX?
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Macrovesicular fatty change in liver, Mucosistis, Teratogenic, myelosuppression (reverse with Leucovorin (Folinic Acid)), fibrotic lung disease, megaloblastic anemia
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How can you reverse Myelosuppression caused by MTX?
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Leucovorin (folinic acid)
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MOA of 5-FU?
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*Pyrimidine analog* that is bioactivated to 5F-dUMP, which covalently complexes folic acid. This then *inhibits thymidylate synthase* by decreasing dTMP and decreasing DNA and protein synthesis
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Uses of 5-FU?
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*Colon cancer* and other solid tumors, *basal cell carcinoma (topical)*
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Toxicity of 5-FU?
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Photosensitivity, Alopecia, Gastric Ulcers
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How do you reverse myelosuppression caused by 5-FU?
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Thymidine. Overdose: "rescue" with Uridine
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MOA of 6-Mercaptopurine (6-MP)?
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*Purine (thiol) analog* that causes a decrease in de novo purine synthesis
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What is 6-MP activated by?
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HGPRTase
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Uses of 6-MP?
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Leukemias and lymphomas (not CLL or Hodgkins)
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What will cause an increase in toxicity of 6-MP?
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Allopurinol because 6-MP is metabolized by xanthine oxidase and Allopurinol will decrease their metabolism which can cause aplastic anemia
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What drug has the same MOA of 6-MP?
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6-TG (thioguanine)
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What is an anti metabolite that is used to treat ALL?
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6-TG (Can be given with Allopurinol)
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MOA of cytarabine (are-C)?
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*Pyrimidine analog* that *inhibits DNA polymerase*
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Use of Cytarabine?
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AML, ALL, *high grade non hodgkins lymphoma*
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Toxicity of Cytarabine?
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Leukopenia, thrombocytopenia, megaloblastic anemia (PanCYTopenia)
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What are the anti tumor antibiotics?
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Dactinomycin, Doxorubicin, Bleomycin, Etoposide
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MOA of Dactinomycin?
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Intercalates in DNA
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What is used for treatment of childhood tumors?
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Dactinomycin
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MOA of Doxorubicin?
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Generates free radicals. Noncovalently intercalate in DNA which causes DNA to break and decreases replication
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What is Doxorubicin used to treat?
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Hodgkins lymphoma, myeloma, sarcomas, solid tumors (breast, ovary, lung)
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AE of Doxorubicin?
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Cardiotoxicity
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What should be given to a patient on Doxorubicin to prevent dilated cardiomyopathy?
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Dexrazoxane (iron chelating agent)
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MOA of Bleomycin?
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Induces free radical formation, which causes breaks in DNA strands
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What is used to treat testicular cancer and Hodgkins lymphoma?
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Bleomycin
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AE of Bleomycin?
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Pulmonary fibrosis
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Etoposide MOA?
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Inhibits topoisomerase II leading to an increase in DNA degradation
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What is used to treat small cell carcinoma of the lung and prostate as well as testicular carcinoma?
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Etoposide
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What drugs are alkylating agents?
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Cyclophosphamide, ifosfamide, Nitrosoureas, Busulfan
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MOA of Cyclophosphamide?
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Covalently X-linked DNA at guanine N-7.
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What does cyclophosphamide require bioactivation by?
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The liver
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What alkylating agent is used for non hodgkins lymphoma, breast and ovarian carcinomas?
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Cyclophosphamide; Ifosfamide
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Toxicity of Cyclophosphamide?
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Hemorrhagic cystitis
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How can you partially prevent the hemorrhagic cystitis that is caused by Cyclophosphamide?
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Mesna (thiol group of mesna binds toxic metabolite)
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What is used in the treatment of brain tumors?
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Nitrosoureas because they are able to cross the BBB
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What are the Nitrosoureas?
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Carmustine, Lomustine, Semustine, Streptozocin
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Busulfan MOA?
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Alkylates DNA (Cell Cycle nonspecific; cross links DNA)
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What is used in the treatment of CML as well as used to ablate patients bone marrow before bone marrow transplantation?
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Busulfan
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AE of Busulfan?
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Pulmonary fibrosis, Hyper pigmentation
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What are the microtubule inhibitors?
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Vincristine, Vinblastine, Paclitaxel
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MOA of Vincristine and Vinblastine?
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Alkaloids that bind to tubulin in the *M phase* and block polymerization of microtubules so that mitotic spindle cannot form
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AE of Vincristine?
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Neurotoxicity; peripheral neuropathy
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Paclitaxel MOA?
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Hyperstabalizes polymerized microtubules in *M phase* so that mitotic spindle cannot break down
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Cisplatin and Carboplatin MOA?
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Cross link DNA; Inhibit DNA biosynthesis
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Use of Cisplatin and Carboplatin?
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Testicular, bladder, ovary and lung carcinomas
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AE of Cisplatin and Carboplatin?
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Nephrotoxic and acoustic nerve damage
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How can you prevent nephrotoxicity of Cisplatin and Carboplatin?
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Amifostine (thiol based cytoprotective free radical scavenging agent) and chloride diuresis (Cisplatin stays in a nonreactive state when in higher Chloride concentration)
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MOA of Hydroxyurea?
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*Inhibits ribonucleotide reductase* leading to a decrease in DNA synthesis (*S phase specific*)
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Drug that is used in Melanoma, CML, SCD (increased HbF)?
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Hydroxyurea
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What is the most commonly used glucocorticoid used in cancer chemo?
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Prednisone: may trigger apoptosis
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Why is there an increased risk of endometrial carcinoma with Tamoxifen use?
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It has partial agonist effects on the endometrium
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Why is there no increased risk of endometrial carcinoma with Raloxifene use?
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It is an endometrial antagonist
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MOA of Trastuzumab (Herceptin)?
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Monoclonal Ab against HER-2 (erb-B2), a tyrosine kinase
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AE of Trastuzumab?
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Cardiotoxicity
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Imatinib (Gleevac) MOA?
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Philadelphia chromosome bcr-abl tyrosine kinase inhibitor
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What is used to treat CML and GI stromal tumors?
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Imatinib (Gleevac)
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Rituximab MOA?
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Monoclonal Ab against CD20 which is found on most B cell neoplasms
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Use of Rituximab?
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Non Hodgkins lymphoma, RA (with MTX)
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What is the MOA of Irinotecan and Topotecan?
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Inhibit topoisomerase I and prevent DNA unwinding and replication
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What is Irinotecan used to treat?
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Colon cancer
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What is Topotecan used to treat?
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Small cell lung cancer and ovarian cancer
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MOA of Vemurafenib?
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Small molecule inhibitor of forms of the B-Raf Kinase with the V600E mutation
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Use of Vemurafenib?
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Metastatic melanoma
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MOA of Bevacizumab?
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Monoclonal Ab against VEGF. Inhibits angiogenesis
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Use of Bevacizumab?
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Solid tumors (colorectal cancer, RCC)
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Toxicity of Bevacizumab?
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Hemorrhage and impaired wound healing
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TX of Hodgkins?
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"ABVD" Adriamyicin/Doxorubicin Bleomycin Vinblastine Dacarbazine
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Use for Temzolomide?
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Treatment of resistant gliomas and anaplastic astrocytomas
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AE of Prednisone?
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Central obesity, muscle breakdown, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis
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What is used in post menopausal women to treat metastatic breast cancer?
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Aromatase inhibitors
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Cetuximab MOA?
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Targets epidermal growth factor receptor on surface of cancer cells (AE: hypotension, interstitial lung disease)
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Neutropenic fever is what?
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Complication of previous chemo, leads to severe anemia, neutropenia and thrombocytopenia
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TX for Neutropenic fever?
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G-CSF: stimulates immature neutrophils to differentiate in bone marrow
