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132 Cards in this Set

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what is the "log kill" hypothesis of anticancer agents?
states that cytotoxic anticancer agents kills a certain percentage of cells, rather than a fixed number.
cell cycle specific drugs act on …?
proliferating cells (usually also cycle phase specific)
dose dependent anticancer drugs act on …?
non proliferating cells, they are dose dependent and cell cycle independent.
what most often determines the upper limit of chemo tolerability?
bone marrow supression
what ccs anticancer agent acts in G2?
bleomycin
what ccs anticancer agents act in M?
vinblastine, vincristine, pacilitaxel
what are the dose dependent anticancer agents?
alkyating agents, antitumor antibiotics, nitrosoureas, dacarbazide, and cisplatin
What ccs anticancer agents act in S?
cytarabine, 6-mercaptopurine, 6-thioguanine, methotrexate, hydroxyurea
where in the cell cycle does etopside act?
in the transition from S to G2.
what is the MOA of methotrexate?
inhibits DHF reductase (folic acid synthesis) - S phase
when is methotrexate used clinically?
leukemia, lymphoma, breast ca, rhematoid arthritis, and psoriasis
what are the sfx of methotrexate?
BMS (leucovorin rescue)
what is leucovorin?
folinic acid, used for rescue from sulfas and methotrexate and dapsone
what is the MOA of cyclophosphamide?
alkylating agent, G0, nucelophillic attack on guanine N7 -> dysfunctional DNA
what is the most commonly used alkylating agent?
cyclophosphamide
when is cyclopohsphamide used clinically?
non-hodgkins, neuroblastoma, ovarian, breast ca, DOC for Wegeners granulomatosis
what is the primary sfx of cyclophosphamide?
BMS (also hemorrhagic cystitis)
what drug is cyclophosphamamide given with and why?
MESNA: b/c it traps the acrolein byproduct and decreases renal and bladder toxicity
what is 4-hydroperoxychyclophosphamide?
a common bone marrow purging agent
what is the mechanisms of cisplatin?
alkylating agent - cross links DNA strands (CCNS but most active in S phase)
when is cisplatin used clinically?
solid tumors, testicular tumors, ovarian carcinoma, bladder, head, neck, lung
what is the most effective anticancer agent for solid tumors?
cisplatin
what are the sfx of cisplatin?
neprhotoxicity and neurotoxicity
how can you decrease the nephrotoxicity of cisplatin?
give with fluids and mannitol.
when can you use carboplatin (an agent similar to cisplatin?)
in ovarian cancer if pt is unable to tolerate cisplastin.
what is doxorubicin?
an antineoplastic
what is the moa of doxorubicin?
CCNS intercalates DNA, forms free radicals, and inhibits topoisomerase
when is doxorubicin used clinically?
leukemia, lymphoma, mm, ewings, kaposi,
what are the sfx of doxorubicin?
cardiomyopathy, bms, and gi upset are dose limiting
what is vincristine?
and M phase specific antineoplastic
what is the MOA of vincristine?
binds tubulin and blocks mitosis
when is vincristine used clinically?
leukemia, lymphomas, wilms, brain, rhabdomyosarcoma, hodkins (MOPP)
what is the dose limiting sfx of vincristine?
peripheral neruopathy
what is vinblastine?
and M phase specific antineoplastic
when is vinblastine used clinically?
testicular ca, kaposis, and hodgkins (ABVD)
what is the MOA of vinblastine?
binds tubulin and blocks mitosis
what is the dose limiting sfx of vinblastine?
bms
what is bleomycin
a G2 specific antitumor antibiotic
what is the MOA of bleomycin?
complexes with Fe and O2 -> DNA strand cuts in G2
when is bleomycin used clinically?
lymphomas, ovarian, and testicular tumors
what is the dose limiting toxicity of bleomycin?
pulmonary fibrosis (10% pts have significant loss of function)
what are the clinical uses of alkylating agnets?
wide range of tumors, cytotoxic to dividing and non dividing cells, can be used against slow growing malignancies
what is the usual dose limiting toxicity of alkylating agnets?
bms
are cisplatin, carboplatin, and mitomycin alkylating agents?
NO. While they do cross link DNA, they do NOT cross link DNA via alkylation … however they are cytotoxic by the same mechanism
mechlorethamine and cyclophosphamide are what?
nitrogen mustard alkylating agents
when is mechlorethamine used clinically?
HL (MOPP), NHL
when is thiotepa used clinically?
alkylating agent used in BC, ovarian cancer (however largely replaced by nitrogen mustards)
when is carmustine used clinically?
alkylating agent that crosses the BBB, used in meningeal leukemia and brain tumors
when is busulfan used clinically?
an alkylating agent used for chornic granulocytic leukemia
when is mitomycin C used clinically?
used with x-ray to attack hypotoxic tumor cells, adenocarcinomas of stomach, pancrease, and lung
what are the severe sfx of mitomycin c?
severe bms, and the "worst vesicant known to man"
what is 5-fluorouracil?
a S-phase specific antineoplasitc
what is the MOA of 5-flurouracil?
converts 5FU to 5Fdump, prevents DNA synthesis -> thymineless death of the cell
when is 5-flurouracil used clinically?
solid tumors, topically for solar keratosis or bassal cell ca
what are the dose limiting toxicitids of 5FU
bms, gi upset, and alopecia
what is tamoxifen?
a nonsteroidal anti-estrogen that binds to nuclear chromatin and inhibits rna synthesis
what is the clinical use of tamoxifen?
DOC for management of estrogen receptor positive breast cancer
what is cytarabine?
an S-phase antineoplastic
what is the MOA of cytarabine?
inhibits DNA synthesis
when is cytarabine used clinically
acute leukemias
what are the dose limiting toxicities of cytarabine?
bms and gi mucositis
what is hydroxyurea?
and S-phase antineoplastic
what is the moa of hydroxyurea/.
inhibits ribonucleotide reductase -> impaired dna synthesis
when is hydroxyurea used clinically?
CML (historically to increase potency of HIV regimens)
what is the dose limiting toxicity of hydroxyurea?
bms
what is mercaptopurine?
an Sphase specific antineoplasitc
what is the moa of mercaptopurine?
inhibits purine ring sytnehsis, and nucleotide interconversion - > inhibits dna synthesis
when is mercaptopurine used clinically?
in some leukemias, and as an immunosupressant in IBD
what is the typical dose limiting toxicity of mercaptopurine?
bms
how is prednisone used clinically to treat neoplasms?
childhood ALL, undifferentiated childhood lymphomas - used with vincristine and antracycline +/- mtx to induce reminssion and then as continuous remission maintenance with mtx
what is pentostatin?
and S-phase antineoplastic
what is the moa of pentostatin?
dATP anolog prevents de novo pruine synthesis - >inhibit dna synthesis
when is pentostatin used clinically?
hairy cell leukemia and T cell lymphomas
what is the dose limiting toxicity of pentostatin?
bms
what is dactinomycin?
a ccns antineoplastic
what is the moa of dactinomycin?
intercalates dna and blocks rna synthesis
when is dactinomycin used clinically?
rhabdomyosarcoma and wilms in children, ewings, and choriocarcinomas
what is the dose limiting toxicity of dactinomycin?
bms and gi upset
what is etopside?
a ccs specific antineoplastic that acts in late S to G2 phase of cell cycle
what is the moa of etopside?
induce strange breakage via DNA topoisomerase inhibition
when is etopside used clinically?
testicular, ovarian, lung ca, lymphomoa, aml, kaposi, osteo, neuroblastomas
what are the dose limiting sfx of etopside?
leukopenia, gi upset, and an usually hig rate of secondary leukemias in chidlren treated with etopside
what is 6-thioguianine?
an S phase specific antineoplastic antimetabolite
what is the moa of 6-thioguianine?
prodrug that inhibits purine synthesis, cuases dysfunctional rna (the same as 6-MP but 6TG has fewer indications and fewer side effects)
what is the clincal use of 6 thioguanine?
aml
what is the dose limiting sfx of 6 thioguianine?
bms
what is herceptin?
an antitumor monoclonal AB that binds her/neu antigen present on 1/4 of bcs (usually more aggressive)
what is the clinical use of herceptin?
breast cancer if express her/neu
what are the sfx of herceptin?
hypersensitivity rxns, chf, increased cardiotoxicity of doxorubicin
what is GM-CSF
an antineoplastic signal that simulates PMNs, macrophages, and eosinophils
when is GM-CSF used clinically?
recovery from bmt
what does G-CSF do?
stimulates pmn production
when is G-CSF used clinically?
prevent chemo induced neutropenia
how is IL-2 used in cancer treatment?
stimulates T cell production leads to malignant cell cytolysis, in advanced malignant melanoma
what antineoplastics cause marked renal toxicity?
cisplatin, methotrexate
what antineoplastics causemarked hepatic toxicity?
6MP, busulfan, cyclophosphamide
what antineoplastics cause marked pulmonary toxicity?
busuflan, bleomycin, procarbazine
what antineoplastics cause marked cardiotoxicity?
doxorubicin, daunorubicin
what antineoplastics cause marked neurologic toxicity?
vincristine, cisplatin, paclitaxel
what antineoplastics are immunosupressive
cyclophosphamide, cytarabine, dactinomycin, methotrexate
what antineoplastic causes hemorrhagic cystitis and how do you treat it
cyclophosphamide
what antineoplastic has leukemia as a potential sfx?
procarbazine
what antineoplastic may lead to pancreatitis?
asparaginase
which antineoplastics are bone marrow sparing?
cisplatin, bleomycin, vincristine, asparaginase
what is cyclosporine?
an immunosuppressant
what is the moa of cyclosporine?
inhibit cmi by blocking IL2 dependent growth and differentiation of T cells
when is cyclosporine used clinically?
doc: for organ or tissue transplant, topically (tacromalis) to treat atopic dermatitis, and on stents (sirolimus) to minimize restenosis after angioplasty
what are the sfx of cyclosporine?
peripheral neruopathy, nephrotoxicity, gingival overgrowth
what is azathioprine?
an immunosuppressant
what is the moa of azathioprine?
converted to 6MP - inhibits dna synthesis
what is the clincal use of azathrioprine?
ra, immunosupression for renal transplant
what is RhoGam
human IgGxRBCRhd antigen - used to prevent hemolytic dz of newborn in subsequent pregnancy to an Rh- mom (also use during miscarriage for same reason)
what is etanercept and when is it used?
an immunomodulator that binds TNF and is used to treat RA, and psoriasis
what is thalidomide and when is it used?
an immunmodulator - suppresses TNFa production, used for the skin manifefstations of lupus and leprosy - DO NOT USE IN PREGNANCY
what is ANTI-CD3 and when is it used?
monoclonal AbxTcellCD3 - impairs antigen recognition and suprresses immune system: used to prevent allograft rejection.
what is ALG and when is it used?
antilymphocytic globluin - polyclonal AbxTcell: used to decrease cmi and treat allograft rejection, sfx include serum sickness and nephritis
abciximab, daclixumab, infliximab, muromonab, palivizumab, rituximab, and trastuxumab are all examples of what?
monoclonal antibodies
what mab is used to as antiplatelet therapy?
abciximab - AbxIIbIIIaR.
what mabs are used in kidney transplant?
daclixumab, muromonmab
what mab is used in ra and chrons disease?
infliximab - AbxTNF
what mab is used to treat rsv?
palivizumab - AbxRSV
what mab is used to treat NHL?
rituximab - AbxNHLsuface protein
what mab is used to treat some aggressive breast cas?
trastuzumab (herceptin) Abxher2/neuR.
what is aldesleukin and when is it used?
IL2: increase T differentiation and NK cells in renal cell ca and metastatic melanoma
when is IL11 used clinically?
in thrombocytopenia to induce platelet formation
what is filgrastim?
G-CSF for marrow recovery
what is sargramostim?
GM-CSF for marrow recovery
when is erythropoeitin used?
anemia, especially associated with renal failure
when is thrombopoietin used?
thrombocytopenia
when is Ifa used?
hep B, hep C, leukemia, and melanoma
when is IF B used?
MS
when is IF y used?
CGD to increase TNF