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77 Cards in this Set
- Front
- Back
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What are the 8 alkylating agents?
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Busulfan
Lomustine carmustine Cyclophosphamide Procarbazine Cisplatin Carboplatin Oxaliplatin |
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what are the two metabolic inhibitors?
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MTX
Pemetrexed |
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what are the 8 inhibitors of DNA synthesis?
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6-Mercaptopurine
6-Thioguanine Fludarabine Cladribine 5-Fluorouracil Capecitabine Cytarabine Gemcitabine |
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what are the 9 plant alkaloids?
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Vinblastine
Vincristine vinorelbine paclitaxel doxetaxel etoposide (VP-16) Teniposide (VP-26) Topotecan irinotecan |
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what are the 8 antitumor antibiotics?
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doxorubicin
daunorubicin idarubicin epirubicin mitoxantrone bleomycin dactinomycin mitomycin |
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what are the 9 hormonal agents?
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prednisone
tamoxifen flutamide bicalutamide leuprolide goserelin anastrozole letrozole exemestane |
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what are the 3 antibodies?
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bevacizumab
rituximab trastuzumab |
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what are the 2 tyrosine kinase inhibitors?
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imatinib
nilotinib |
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what categories of drugs are cell cycle specific agents? what is the exception?
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antimetabolites
epipodophyllotoxins taxanes vinca alkaloids exception: Bleomycin-- antitumor antibiotic (only cell cycle-specific agents) |
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what categories of drugs are cell cycle nonspecific agents?
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alklyating agents
anthracyclines antitumor antibiotics: (dactinomycin, mitomycin) camptothecins platinum analogs |
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what are the 9 drugs that fall under the antimetabolites?
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Capecitabine
Cladribine Cytarabine Fludarabine 5-Fluorouracil (5-FU) Gemcitabine 6-Mercaptopurine (6-MP) Methotrexate (MTX) 6-Thioguanine (6-TG) |
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what are the three antitumor antibiotics?
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dactinomycin
mitomycin bleomycin |
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what are the two epiodophyllotoxins?
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etoposide
teniposide |
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what are the three taxanes?
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albumin-bound paclitaxel
docetaxel paclitaxel |
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what are the three vinca alkaloids?
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vinblastine
vincristine vinorelbine |
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what are the 7 alkylating agents?
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Busulfan
Carmustine Cyclophosphamide Lomustine Mechlorethamine Melphalan Thiotepa |
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what are the 5 anthracyclines?
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Daunorubicin
Doxorubicin Epirubicin Idarubicin Mitoxantrone |
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what are the 2 camptothecins?
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irinotecan
topotecan |
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what are the 3 platinum analogs?
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Carboplatin
Cisplatin Oxaliplatin |
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what are the 5 ways of uncontrolled growth for malignant cancer?
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growth factor receptor signaling
regulators of cell cycle effectiveness of apoptosis telomerase expression local blood supply (angiogenesis) |
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malignant cells possess what 5 characteristics?
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-ability to accumulate mutations
-uncontrolled growth -capacity for dedifferentiation and loss of function -invasiveness -inability to metastasize |
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Expression of what enzyme is used to increase the invasiveness of a malignant cancer cells?
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metalloproteases
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what is log kill?
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A given dose of a cytotoxic drug destroys a constant fraction of the malignant cells.
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explain what is going on in each compartment. What drugs are they susceptible to?
A? B? C? |
A- dividing cells continuously in the cell cycle. susceptible to cytotoxic drugs
B- Resting cells in G0 phase; not dividing, but may be able to begin dividing. Not very susceptible to available cytotoxic drugs, but may enter compartment A after tx w/ cytotoxic drugs. c- cells that are not able to divide, but contribute to the mass of the tumor- not a tx problem. |
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what is the general mechanism of chemotherapeutic agents?
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primarily to prevent cell division with no specific effect on invasiveness, loss of differentiation or ability to metastasize.
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what type of tumors are txed by cell-cycle specific? cell-cycle non-specific?
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cell-cycle specific: hematologic malignancies, solid tumor w/ large growth fraction
cell-cycle non specific: solid tumors w/ low or high growth fraction |
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what are the acute responses to tissue toxicity d/t chemotherapeutic agents? chronic responses?
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Acute: considered reversible
-N/V -Bone marrow suppresion, alopecia (neutropenia and thrombocytopenia) chronic: -leukemia -cardiotoxicity -sterility, neuropathy, nephropathy |
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what is the MOA of alkylating agents? what does it result in? what are they most effective against?
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They transfer their alkyl group to various cellular constituents and most of the alkylating agents are bifunctional allowing cross-linking w/n a DNA strand or btwn 2 DNA strands. This results in miscoding, depurination and strand breakage--> cytotoxic effects. They are most effective against actively cycling cells (compartment A)
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what is a delayed adverse effects of busulfan?
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pulmonary fibrosis, hepatic toxicity
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which member of the alkylating agents family must be activated in the liver?
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cyclophosphamide
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what can acrolein lead to? what is it? how do you prevent it from causing this?
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it is a bischloroethyl amine and a cytotoxic metabolic. It may lead to hemorrhagic cystitis. Add Mesna to your acrolein regement and mesna will form an inactive compound with it.
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what are the therapeutic uses of bischloroethyl amines?
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Non-hodgkin's lymphoma, ovarian, breast cancer, neuroblastoma
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what are the adverse affects of procarbazine?
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bone marrow suppression, pulmonary toxicity, neurotoxicity, leukemogenic, teratogenic
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what is the MOA of platinum analogs? what are their therapeutic uses?
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they form complexes that react w/ DNA forming intra- and interstrand cross-links causing cytotoxic effects.
TU: solid tumors: testicular, ovarian, bladder, lung cancer |
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what are the adverse effects of platinum analogs?
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nephrotoxicity, ototoxicity
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what second generation platinum anaglog has replaced cisplatin? what is the main dose-limiting toxicity of this drug?
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Carboplatin
toxicity: myelosuppression |
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Chemotherapeutic drugs are often associated w/ all of the following adverse effect except?
1- alopecia 2- jaundice 3- mucositis |
2- jaundice
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what is the general MOA of antimetabolites?
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targets differences in metabolism hat leave cancerous cells more vulnerable than normal cells. These agents typically target major enzymes in these pathways "bottlenecks".
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what is the MOA of MTX? what are its adverse effects?
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MOA: MTX is a folic acid antagonist, binding to the active site of DHFR (dihydrofolate reductase) and preventing the production of the reduced form of folate. Interferes w/ the formation of DNA, RNA, and key cellular proteins.
adverse: Mucositis, bonemarrow depression, nephrotoxicity, and class X |
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What can prevent the adverse effects of MTX? what are the therapeutic uses of MTX?
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leucovorin (replaces FH4)
TU: leukemias, lymphomas, breast cancer |
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what drug in the antimetabolites family has thymidilate synthetase as its main site of action?
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Pemetrexed.
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what must the 6-thiopurines be converted by in order to be in its active form?
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converted by hypoxanthine guanine phosphoribosyl transferase (HGPRT)
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what are the two categories of genetic changes that are important for carcinogenesis?
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activation of proto-oncogenes to oncogenes and inactivation of tumor suppressor genes
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T/F
Nitrosoureas can cross the BBB? |
True.
They are lipid soluble. |
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What are the adverse effects of bischloroethyl amines?
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hemorrhagic cystitis and hepatic toxicity
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T/F
MTX crosses the BBB. |
FALSE
It can be administered intrathecally to act on the brain, but it does not cross the BBB |
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what cause the 6-thiopurines cause? (toxicity) what is the therapeutic use of 6-thiopurines?
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Myelosuppression, immunosuppression, hepatotoxicity.
TU: Acute lymphocytic Leukemia |
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how can fludarabine and cladribine interfere w/ DNA synthesis/ repair?
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by being phosphorylated to its triphosphate form which inhibits DNA polymerase alpha and beta.
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what is the MOA of 5-fluorouracil? what else is administered w/ 5-FU?
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5-FU is a prodrug that undergoes biotransformations and becomes FdUMP which then forms a ternary complex w/ thymidylate synthetase and reduces folate preventing synthesis of thymidine. 5-FU can also be incoporated into RNA and DNA messing up synthesis and translation.
Leucovorin is administered w/ 5-FU because it potentiates the actions of 5-FU by stabilizing the ternary complex. |
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what are the adverse effects of 5-FU and the therapeutic uses?
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adverse: Nausea, diarrhea, mucositis, bone marrow depression, alopecia
TU: Breast, ovarian, head and neck cancers. |
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what other drug has the same MOA as 5-FU?
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capecitabine
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what drug is S-phase specific and its activity is limited to hematologic malignancies? what other drug works in the same manner by inhibiting DNA polymerase alpha and beta?
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Cytarabine; cladribine
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what is MOA of gemcitabine?
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must be phosphorylated to become active- inhibits ribonucleotide reductase which decreases the pool of nucleotides for DNA synthesis. This will cause DNA chain termination following its incorporation into the DNA.
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what is the MOA for the vinca alkaloids?
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inhibit tubulin polymerization and bind to B-tubulin and prevent interaction w/ alpha tubulin preventing assembly of microtubules. This causes cell division to halt at metaphase which leads to apoptosis.
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what is the length of tubulin in a cell determined by? how do microtubules grow during assembly?
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the speed of assembly vs the speed of disassembly. The rate of assembly is greater than the speed of disassembly and that causes microtubules grow.
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what are the adverse effects of vinblastine? vincristine? vinorelbine?
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vinblastine: Myelosupression (Bone marrow suppression) and GI problems
Vincristine: Limited myelosuppression, neurotoxic effects (numbness, tingling), less often cause GI symptoms. Vinorelbine: Myelosuppressive activity is intermediate, granulocytopenia is the main toxicity. Low likelihood of neurotoxicity. |
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what are the therapeutic uses of Vinblastine and vincristine?
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vinblastine: Hodgkin, NHL, breast cancer, testicular
Vincristine: ALL, hodgkin, leukemias, wilms |
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what is the MOA of taxanes?
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binds to a different site on B-actin to promote formation of microtubules. This leads to the formation of atypical microtubule structures during the M phase. This arrest mitosis and apoptosis leads to cell death.
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what are the adverse effects of taxanes?
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myelosuppression, cumulative neurotoxicity and HSN reaction
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what is the MOA of the epipodophyllotoxins?
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they inhibit DNA topoisomerase II by forming a ternary complex composed of topoisomerase II, the DNA, and the drug leading to strand breakage. This blocks cell division in the late S-G2 phase.
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Which of the following agents is a cell cycle-specific agent? (appropriate for lymphoma?)
1. MTX 2. Cisplatin 3. Cyclophosphamide |
1. MTX
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what is the MOA of camptothecins? which one needs to be converted to its active form?
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inhibit the activity of topoisomerase I. It stabilize strands breaks and prevent strand ligation which leads to DNA damage
Irinotecan- must be converted to its active form. |
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what is the MOA of anthracyclines?
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Minor: insert btwn base pair of DNA and RNA and disrupt its function
Major: inhibition of topoisomerase II leading to DNA strand breakage. -generation of superoxide free radicals leads to DNA strand breakage. |
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what are the adverse effects of anthracyclines?
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myelosuppression and cardiotoxicity
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what is the MOA of bleomycin? what are the adverse effects of bleomycin?
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MOA: one end binds to DNA and the opposite end chelates Fe2+. Oxidation of this complex causes DNA fragmentation and stops the cell cycle at G2.
AE: Pulmonary fibrosis is a dose-limiting toxicity and mucocutaneous reaction (often involving palms of feet and hands) |
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what is the MOA of Dactinomycin (actinomycin D)?
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intercalation and inhibition of topoisomerase II
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what is the MOA of mitomycin?
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metabolically activated into an alkylating agent that cross-links DNA.
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what is the MOA of prednisone?
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coverted by 11-b-hydroxysteroid dehydrogenase to prednisolone. Prednisolone acts through the glucocorticoid receptor and causes lymphocytopenia and decreases lymphoid mass.
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what is the MOA of tamoxifen?
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competitive partial agonist inhibitor of estrogen (which is what causes breast cancer tumors to grow) and has a lower affinity than estradiol at the estrogen receptor.
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what is the MOA of flutamide and bicalutamide?
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antagonist at the androgen receptor which will prevent testosterone formation which will inhibit the growth of prostate tumors.
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what is the MOA of leuprolide and goserelin?
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initially cause a surge in LH and FSH followed by inhibition of their release and the release of testosterone (to near castration levels)
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what is the MOA of anastrozole, letrozole, exemestane? which one is an irreversible inhibitor of aromatase?
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inhibit the conversion of estrogen from androgens by aromatase. Exemastane is an irreversible inhibitor.
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what is the MOA of monoclonal antibodies?
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cytotoxicity: antibody dependent lysis, complement dependent cell lysis, localized delivery of radiation, localized delivery of chemotherapy and inhibit angiogenesis.
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which monoclonal antibody inhibits angiogenesis? which one binds to CD20 and what does it cause? whcih one binds to Her-2?
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Bevacizumab (colon and lung) binds to circulating VEGF inhibiting angiogenesis.
Rituximab (NHL): binds to CD 20 causing antibody dependent or complement dependent cell lysis Trastuzumab (breast cancer): binds to HER-2 causing antibody dependent lysis of cells. |
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what is the MOA of Imatinib and nilotinib?
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inhibitor of platelet derived growth factor and intracellular kinase pathways.
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what can you combine MTX w/ to decrease the likelihood of developing resistance?
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vincristine
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what are the three bone marrow sparing agents?
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cisplatin, bleomycin and vincristine
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