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Pharm - Cancer chemotherapy
pharmacology of cancer chemotherapy agents
225
Pharmacology
Professional
04/13/2012

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Cards

Term
Antimetabolites act during the ___ phase
Definition
S
Term
Podophyllotoxins act during which cell cycle phases?
Definition
S and G2
Term
Bleomycin acts during the ____ phase
Definition
G2
Term
Vinca alkaloids act during the __ phase
Definition
M
Term
Which drugs act during the S phase?
Definition
antimetabolites and podophyllotoxins
Term
which drugs act during the G2 phase?
Definition
podophyllotoxins and bleomycin
Term
which drug acts only during G2?
Definition
bleomycin
Term
which drugs act during M phase?
Definition
vinca alkaloids
Term
Increased DNA repair can be responsible for resistance, especially for which drugs?
Definition
alkylating agents and cisplatin
Term
alkylating agents and cisplatin -- method of resistance?
Definition
increased DNA repair
Term
Formation of thiol trapping agents - resistance to which drugs?
Definition
bleomycin, cisplatin, anthracyclines
Term
bleomycin, cisplatin, anthracyclines -- resistance mechanism?
Definition
formation of thiol trapping agents
Term
changes in dihydrofolate reductase and increased synthesis of the enzyme are methods of resistance to which drug?
Definition
methotrexate
Term
method of resistance to methotrexate?
Definition
increased synthesis of or change in dihydrofolate reducatase
Term
resistance to purine and pyrimidine antimetabolites can result from...
Definition
decrease in activity of enzymes needed to convert them to cytotoxic metabolites
Term
Decreasing the activity of enzymes needed to convert prodrugs to active cytotoxic metabolites is a method of resistance against which drugs?
Definition
purine and pyrimidine antimetabolites
Term
increased activity of enzymes capable of inactivating cancer drugs is a method of resistance to most of the...
Definition
purine and pyrimidine antimetabolites
Term
How do cancer cells produce an accelerated efflux of many drugs?
Definition
increased expression of a normal gene (MDR1) for a cell surface glycoprotein
Term
increased expression of a normal gene (MDR1) for a cell surface glycoprotein results in...
Definition
accelerated efflux of many drugs
Term
the alkylating agents include which broad groups?
Definition
nitrogen mustards, nitrosoureas, alkylsulfonates
Term
nitrogen mustards, nitrosoureas, alkylsulfonates - what type of drugs are these?
Definition
alkylating agents
Term
Which drugs act in PART as alkylating agents?
Definition
cisplatin, dacarbazine, procarbazine
Term
cisplatin, dacarbazine, procarbazine - these act in PART as ...
Definition
alkylating agents
Term
name the nitrogen mustards
Definition
chlorambucil, cyclophosphamide, mechlorethamine
Term
chlorambucil, cyclophosphamide, mechlorethamine - what are these?
Definition
nitrogen mustards
Term
name the nitrosoureas
Definition
carmustine, lomustine
Term
carmustine, lomustine - what are these?
Definition
nitrosoureas
Term
name an alkylsulfonate
Definition
busulfan
Term
bulsulfan - what is it?
Definition
alkylsulfonate
Term
Are the alkylating agents CCS or CCNS?
Definition
CCNS
Term
Alkylating agents act on nucleophilic groups on DNA bases, particularly...
Definition
N-7 of guanine
Term
Which drugs act on N-7 of guanine and other nucleophilic groups on DNA bases?
Definition
alkylating agents
Term
What does alkylating bases do?
Definition
leads to cross-linking, abn base-pairing, DNA strand breakage
Term
What enzyme is needed for antitumor activity of cyclophosphamide?
Definition
p450
Term
p450 enzymes are needed for antitumor activity of...
Definition
cyclophosphamide
Term
one of the breakdown products of the biotransformation of cyclophosphamide is...
Definition
acrolein
Term
what is acrolein?
Definition
a breakdown product of the biotransformation of cyclophosphamide
Term
Tox of cyclophosphamide?
Definition
GI distress, myelosuppression, alopecia, hemorrhagic cystitis (acrolein), cardiac dysfunct, pulm tox, SIADH
Term
What can be used to decrease hemorrhagic cystitis from cyclophosphamide?
Definition
mesna
Term
what is mesna used for?
Definition
decreasing hemorrhagic cystitis from cyclophosphamide
Term
Name the drug - Tox: GI distress, myelosuppression, alopecia, hemorrhagic cystitis (acrolein), cardiac dysfunct, pulm tox, SIADH
Definition
cyclophosphamide
Term
mechlorethamine - MOA?
Definition
spontaneously converts to cytotoxic product
Term
which drug spontaneously converts to cytotoxic product?
Definition
mechlorethamine
Term
mechlorethamine - used for what?
Definition
Hodgkin's lymphoma
Term
which drug is best known for use in Hodgkin's lymphoma?
Definition
mechlorethamine
Term
Mechlorethamine - tox?
Definition
GI distress, myelosuppression, alopecia, sterility. Marked vesicant actions.
Term
Name the drug - Tox: GI distress, myelosuppression, alopecia, sterility. Marked vesicant actions.
Definition
mechlorethamine
Term
cisplatin, carboplatin, oxaliplatin are what?
Definition
platinum analogs
Term
Cisplatin is used IV, distributes to most tissues and is cleared...
Definition
in unchanged form by kidney
Term
what is oxaliplatin used for?
Definition
advanced colon cancer
Term
Cisplatin - tox?
Definition
GI, mild hematotoxicity, neurotoxic, nephrotoxic (can be reduced with mannitol and forced hydration).
Term
Name the drug - Tox: GI, mild hematotoxicity, neurotoxic, nephrotoxic (can be reduced with mannitol and forced hydration).
Definition
cisplatin
Term
How does toxicity of carboplatin compare to cisplatin?
Definition
less nephrotoxic, less likely to cause tinnitus and hearing loss, more likely to cause myelosuppression
Term
Compares to cisplatin, which drug is less nephrotoxic, less likely to cause tinnitus and hearing loss, but more likely to cause myelosuppression?
Definition
carboplatin
Term
Oxaliplatin causes dose-limiting...
Definition
neurotoxicity
Term
which platinum analog causes dose-limiting neurotoxicity?
Definition
oxaliplatin
Term
procarbazine - MOA?
Definition
forms hydrogen peroxide, generates free radicals, causes DNA strand scisson
Term
Which drug forms hydrogen peroxide, generates free radicals, causes DNA strand scisson?
Definition
procarbazine
Term
procarbazine is orally active, penetrates into most tissues, including CSF, and is eliminates via...
Definition
hepatic metabolism
Term
What is the primary use of procarbazine?
Definition
hodgkin's lymphoma
Term
Procarbazine - tox?
Definition
myelosuppressant, GI, CNS dysfunct, peripheral neuropathy, skin rxns, inhibits MAO and hepatic enzymes, causes disulfiram-like rxns with ethanol, it's leukemogenic
Term
Name the drug - tox: myelosuppressant, GI, CNS dysfunct, peripheral neuropathy, skin rxns, inhibits MAO and hepatic enzymes, causes disulfiram-like rxns with ethanol, it's leukemogenic
Definition
procarbazine
Term
Busulfan is sometimes used in...
Definition
CML
Term
Busulfan - tox?
Definition
adrenal insufficiency, pulm fibrosis, skin pigmentation
Term
Which drug causes adrenal insufficiency, pulm fibrosis, skin pigmentation?
Definition
busulfan
Term
Carmustine and lomustine are highly ___-soluble drugs used in _____ tumors.
Definition
lipid, brain
Term
Which drugs are highly lipid-soluble drugs used in management of brain tumors?
Definition
carmustine, lomustine
Term
dacarbazine is used in regimens for...
Definition
hodgkin's
Term
dacarbazine: tox?
Definition
alopecia, rash, GI, myelosuppression, phototoxicity, flulike syndrome
Term
Name the drug - tox: alopecia, rash, GI, myelosuppression, phototoxicity, flulike syndrome
Definition
dacarbazine
Term
Name 2 antagonists of purines
Definition
mercaptopurine, thioguanine
Term
mercaptopurine and thioguanine are...
Definition
purine antagonists
Term
Name 3 pyrimidine antagonists
Definition
FU, cytarabine, gemcitabine
Term
FU, cytarabine, gemcitabine- what are these?
Definition
pyrimidine antagonists
Term
Two agents act in the pathway from ribonucleotides to deoxynucleotides. What are they?
Definition
hydroxyurea, gemcitabine
Term
4 agents act in the pathway from deoxynucleotides to DNA. What are they?
Definition
methotrexate, gemcitabine, FU, cytarabine
Term
methotrexate causes a decrease in the synthesis of...
Definition
thymidylate, purine nucleotides and amino acids
Term
which drug causes a decrease in the synthesis of thymidylate, purine nucleotides and amino acids?
Definition
methotrexate
Term
the formation of _____ derivates of methotrexate are important for cytotoxic action
Definition
polyglutamate
Term
Methotrexate is given orally and IV and has good tissue distribution except to..
Definition
CNS
Term
Describe the metabolism/clearance of methotrexate
Definition
not metabolized, clearance is dependent on renal function
Term
why do you need adequate hydration with methotrexate?
Definition
to prevent crystallization in renal tubules
Term
Methotrexate: tox?
Definition
bone marrow spupression, mucositis, hepatotoxicity, pulm infiltrates and fibrosis - enhanced by salicylates, NSAIDs, sulfonamides, sulfonylureas
Term
Name the drug- tox: bone marrow spupression, mucositis, hepatotoxicity, pulm infiltrates and fibrosis - enhanced by salicylates, NSAIDs, sulfonamides, sulfonylureas
Definition
methotrexate
Term
the toxic effects of methotrexate on normal cells may be reduced by administration of...
Definition
leucovorin (folinic acid)
Term
6-MP and 6-TG are activated by...
Definition
HGPRTases
Term
HGPRTases activate which drugs?
Definition
6-MP and 6-TG
Term
how can tumor cells be resistant to 6-MP or 6-TG?
Definition
decreased HGPRTases, increased alkaline phosphatases that inactivate the toxic nucleotides
Term
describe the oral bioavailability of 6-MP and 6-TG
Definition
low due to first pass
Term
The metabolism of ______ by xanthine oxidase is inhibited by allopurinol
Definition
6-MP
Term
allopurinol inhibits the metabolism of...
Definition
6-MP, by xanthine oxidase
Term
purine antimetabolites are used mainly in the ...
Definition
acute leukemias and CML
Term
which drugs are used mainly in the acute leukemias and CML?
Definition
6-MP and 6-TG
Term
FU - MOA?
Definition
converted to 5-FdUMP -> inhibits thymidylate synthase, leads to thymineless death of cells
Term
which drug inhibits thymidylate synthase?
Definition
5-FU
Term
Does 5-FU get into the CSF?
Definition
yes
Term
elimination of 5-FU is mainly via...
Definition
metabolism
Term
Name a drug used for cancers of bladder, breast, colon, head and neck, liver, ovarian, topically for keratoses and BCC
Definition
5-FU
Term
tox of 5-FU?
Definition
GI distress, myelosuppression, alopecia
Term
What is cytarabine?
Definition
a pyrimidine antimetabolite
Term
MOA of cytarabine?
Definition
it's activated by kinases to AraCTP, an inhibitor of DNA polymerases.
Term
which drug is activated by kinases to AraCTP, an inhibitor of DNA polymerases?
Definition
cytarabine
Term
Cytarabine is the drug most specific for the ___ phase
Definition
S
Term
Which drug is MOST specific for the S phase?
Definition
cytarabine
Term
What is gemcitabine?
Definition
a deoxycytidine analog
Term
which drug is a deoxycytadine analog?
Definition
gemcitabine
Term
gemcitabine - MOA?
Definition
it is converted into active diphosphate and triphosphate nucleotide forms and inhibits ribonucleotide reductase. It can also be incorporated into DNA and cause chain termination.
Term
Which drug is converted into active di-and triphosphate nucleotide forms, inhibits ribonucleotide reductase and is incorporated into DNA, causing chain termination?
Definition
gemcitabine
Term
elimination of gemcitabine is mainly by ______
Definition
metabolism
Term
gemcitabine - tox?
Definition
primarily myelosuppression, mainly as neutropenia. pulm tox has been observed
Term
Name the drug - tox: primarily myelosuppression, mainly as neutropenia. pulm tox has been observed
Definition
gemcitabine
Term
plant alkaloids include which groups of drugs?
Definition
vinca alkaloids, podophyllotoxins, camptothecins, taxanes
Term
vinca alkaloids, podophyllotoxins, camptothecins, taxanes -- these are all under which classification?
Definition
plant alkaloids
Term
name 3 vinca alkaloids
Definition
vinblastine, vincristine, vinorelbine
Term
vinblastine, vincristine, vinorelbine - what type of drug are these?
Definition
vinca alkaloids
Term
name 2 podophyllotoxins
Definition
etoposide, teniposide
Term
etoposide, teniposide - what type of drug are these?
Definition
podophyllotoxins
Term
name 2 camptothecins
Definition
topotecan, irinotecan
Term
topotecan, irinotecan - what are these?
Definition
camptothecins
Term
name 2 taxanes
Definition
paclitaxel, docetaxel
Term
paclitaxel, docetaxel - what are these?
Definition
taxanes
Term
vinca alkaloids - MOA?
Definition
block formation of mitotic spindle by preventing assembly of tubulin dimers into microtubules.
Term
Which drugs block formation of mitotic spindle by preventing assembly of tubulin dimers into microtubules?
Definition
vinca alkaloids
Term
Vinca alkaloids act primary during the __ phase
Definition
M
Term
Vinca alkaloids must be given _____
Definition
parenterally
Term
Do vinca alkaloids penetrate the CSF?
Definition
no
Term
How are vinca alkaloids cleared?
Definition
mainly biliary excretion
Term
What is vinorelbine used for?
Definition
non-small cell lung CA, breast CA
Term
Toxicity of vinblastine and vinorelbine?
Definition
GI distress, alopecia, BM suppression
Term
Vincristine does not cause serious ______ but has ______ actions
Definition
myelosuppression, neurotoxic actions
Term
What are the neurotoxic actions of vincristine?
Definition
areflexia, peripheral neuritis, paralytic ileus
Term
etopiside - MOA?
Definition
increase degradation of DNA, possibly via interaction with topisomerase II, also inhibits mitochondrial electron transport
Term
Name the drug- MOA: increase degradation of DNA, possibly via interaction with topisomerase II, also inhibits mitochondrial electron transport
Definition
etoposide
Term
In which phases is etopiside most active?
Definition
late S and early G2
Term
Which drug is most active in late S and early G2?
Definition
etoposide
Term
Which drug is an analog of etopiside with similar characteristics?
Definition
teniposide
Term
what is teniposide?
Definition
analog of etoposide with similar characteristics
Term
Is etoposide absorbed after oral admin? How is it eliminated?
Definition
yes, via kidneys
Term
Tox of etoposide?
Definition
GI irritant, alopecia, BM suppression
Term
topotecan and irinotecan - MOA?
Definition
inhibit topoisomerase I: they damage DNA by inhibiting an enzyme that cuts and relegates single DNA strands during normal DNA repair processes
Term
Name the drugs - MOA: inhibit topoisomerase I: they damage DNA by inhibiting an enzyme that cuts and relegates single DNA strands during normal DNA repair processes
Definition
topotecan and irinotecan
Term
irinotecan is a prodrug that is converted into its active metabolite in the...
Definition
liver
Term
elimination of topotecan and irinotecan?
Definition
topo - renally, irino - bile and feces
Term
what is topotecan used for?
Definition
second line therapy for advanced ovarian CA, small cell lung CA
Term
what is irinotecan used for?
Definition
metastatic colorectal CA
Term
what are the 2 most common toxicities of topotecan and irinotecan?
Definition
myelosuppression and diarrhea
Term
paclitaxel and docetaxel - MOA?
Definition
interfere with the mitotic spindle, prevent microtubule DISASSEMBLY into tubulin monomers
Term
Name the drug: MOA- interfere with the mitotic spindle, prevent microtubule DISASSEMBLY into tubulin monomers
Definition
paclitaxel and docetaxel
Term
How are paclitaxel and docetaxel given?
Definition
IV
Term
the taxanes are used in...
Definition
advanced breast and ovarian CA
Term
Paclitaxel - tox?
Definition
neutropenia, thrombocytopenia, peripheral neuropathy, hypersensitivity rxns during infusion
Term
Name the drug - tox: interfere with the mitotic spindle, prevent microtubule DISASSEMBLY into tubulin monomers
Definition
paclitaxel
Term
docetaxel - tox?
Definition
neurotoxicity and BM suppression
Term
docetaxel - tox?
Definition
neurotoxicity and BM suppression
Term
doxorubicin, daunorubicin, bleomycin, dactinomycin, mitomycin - what class are these?
Definition
antibiotics
Term
doxorubicin and daunorubicin are_____
Definition
anthracyclines
Term
name two anthracyclines
Definition
doxorubicin and daunorubicin
Term
doxorubicin and daunorubicin - MOA?
Definition
intercalate btw base pairs, inhibit topisomerase II, generate free radicals, block synthesis of DNA and RNA, cause DNA strand scission, cause membrane disruption
Term
name the drugs: MOA- intercalate btw base pairs, inhibit topisomerase II, generate free radicals, block synthesis of DNA and RNA, cause DNA strand scission, cause membrane disruption
Definition
doxorubicin and daunorubicin
Term
anthracyclines are CCNS or CCS?
Definition
CCNS
Term
doxorubicin and daunorubicin must be given...
Definition
IV
Term
how are the anthracyclines metabolized/excreted?
Definition
metab in liver, products excreted in bile and urine
Term
The main use of daunorubicin is in the treatment of...
Definition
acute leukemias
Term
idarubicin is approved for use in...
Definition
AML
Term
Anthracyclines - tox?
Definition
BM suppression, GI distress, severe alopecia, CARDIOTOXICITY
Term
What may protect against cardiotoxicity from anthracyclines?
Definition
dexrazoxane
Term
What does dexrazoxane do?
Definition
it's an inhibitor of iron-mediated free radical formation, may protect against cardiotoxicity of anthracyclines
Term
______ formulations of doxorubicin may be less cardiotoxic
Definition
liposomal
Term
bleomycin - MOA?
Definition
generates free radicals, bind to DNA and cause strand breaks, inhibit DNA syn
Term
Name the drug - MOA: generates free radicals, bind to DNA and cause strand breaks, inhibit DNA syn
Definition
bleomycin
Term
Is bleomycin CCS or CCNS?
Definition
CCS
Term
Bleomycin is given ____
Definition
parenterally
Term
Bleomycin is inactivated by tissue ______, but some renal clearance of intact drug also occurs
Definition
aminopeptidases
Term
Bleomycin - tox?
Definition
pulm dysfunction, hypersensitivity reactions, mucocutaneous rxns
Term
Dactinomycin - MOA?
Definition
binds dsDNA and inhibits DNA-dep RNA synthesis
Term
name the drug - MOA: generates free radicals, bind to DNA and cause strand breaks, inhibit DNA syn
Definition
dactinomycin
Term
dactinomycin must be given _____, and intact drug and metabolites are excreted in ____
Definition
parenterally, bile
Term
dactinomycin is used in...
Definition
melanoma and wilm's
Term
tox of dactinomycin?
Definition
BM suppression, skin rxns, GI irritation
Term
MOA of mitomycin?
Definition
metabolized by liver enzymes to form alkylating agent that cross-links DNA
Term
Mitomycin is given ____ and is rapidly cleared via _____
Definition
IV, hepatic metabolism
Term
Clinical use of mitomycin?
Definition
acts against hypoxic tumor cells, used for adenocarcinoma of cervix, stomach, pancreas, lung
Term
Name the drug - acts against hypoxic tumor cells, used for adenocarcinoma of cervix, stomach, pancreas, lung
Definition
mitomycin
Term
tox of mitomycin?
Definition
causes severe myelosuppression, toxic to heart, liver, lung, kidney
Term
What is the most commonly used glucocorticoid in cancer chemotherapy? What is it used for?
Definition
prednisone, leukemias and lymphomas
Term
What is tamoxifen? What is the effect on endometrium?
Definition
SERM, agonist -> ^ risk of cancer
Term
Tox of tamoxifen?
Definition
N/V, hot flashes, vaginal bleeding, venous thrombosis, ^risk endometrial hyperplasia/neoplasia
Term
What is toremifene?
Definition
a newer estrogen recep antagonist used in advanced breast cancer
Term
What is flutamide and what is it used for?
Definition
androgen receptor antagonist used in prostatic carcinoma
Term
Name an androgen receptor antagonist used in prostatic carcinoma
Definition
flutamide
Term
flutamide - tox?
Definition
gynecomastia, hot flashes, hepatic dysfunction
Term
Name the GnRH analogs
Definition
leuprolide, gosrelin, nafarelin
Term
leuprolide, gosrelin, nafarelin - what are these?
Definition
GnRH analogs
Term
Tox of leuprolide?
Definition
bone pain, gynecomastia, hematuria, impotence, testicular atrophy
Term
Name the drug - tox: bone pain, gynecomastia, hematuria, impotence, testicular atrophy
Definition
leuprolide
Term
Name 2 aromatase inhibitors
Definition
anastrozole, letrozole
Term
anastrozole, letrozole - what are these?
Definition
aromatase inhibitors
Term
What does aromatase do?
Definition
androstenedione -> estrone
Term
aromatase inhibitors are used in...
Definition
advanced breast cancer
Term
aromatase inhibitors - tox?
Definition
N/D, hot flashes, bone and back pain, dyspnea, peripheral edema
Term
What does asparaginase do? What's it used for?
Definition
depletes serum asparagine, used in treatment of T cell auxotrophic cancers (leukemia and lymphoma)
Term
Tox of asparaginase?
Definition
hypersensitivity, acute pancreatitis, bleeding
Term
Name the drug - tox: hypersensitivity, acute pancreatitis, bleeding
Definition
asparaginase
Term
What does imatinib do?
Definition
inhibits the TKase activity of protein product of Bcr-Abl oncogene expressed in CML
Term
In addition to CML, imatinib is used for...
Definition
GIST (c-kit TKase is also inhibited)
Term
Tox of imatinib?
Definition
diarrhea, myalgia, fluid retention
Term
Name the drug- tox: diarrhea, myalgia, fluid retention
Definition
imatinib
Term
____-interferons are effective against hairy cell leukemia, early CML and t-cell lymphomas
Definition
alpha
Term
Toxic effects of IFNs?
Definition
myelosuppression and neuro dysfunction
Term
What is rituximab and how does it work?
Definition
monoclonal Ab that binds a surface protein in non-Hodgkin's lymphoma cells and induces complement-mediated lysis, direct cytotoxicity,induction of apoptosis
Term
Name the drug - monoclonal Ab that binds a surface protein in non-Hodgkin's lymphoma cells and induces complement-mediated lysis, direct cytotoxicity,induction of apoptosis
Definition
rituximab
Term
Rituximab is used for...
Definition
low-grade lymphomas
Term
Rituximab use is associated with...
Definition
hypersensitivity rxns and myelosuppression
Term
What is trastuzumab?
Definition
monoclonal Ab against HER-2/neu receptor for epidermal growth factor
Term
name a monoclonal Ab against HER-2/neu receptor for epidermal growth factor
Definition
trastuzumab
Term
trastuzumab - tox?
Definition
nausea, vomiting, chills, fevers, HA. May cause cardiac dysfunction, CHF
Term
Name the drug - tox: nausea, vomiting, chills, fevers, HA. May cause cardiac dysfunction, CHF
Definition
trastuzumab
Term
What is Cetuximab?
Definition
antibody against extracellular domain of EGFR
Term
name an antibody against extracellular domain of EGFR
Definition
cetuximab
Term
what are gefitinib and erlotinib?
Definition
small molecule inhibitors of the EGFR TK domain
Term
name the small molecule inhibitors of the EGFR TK domain
Definition
gefitinib, erlotinib
Term
what are the main toxicities of gefitinib and erlotinib?
Definition
rash and diarrhea
Term
What is bevacizumab?
Definition
monoclonal Ab that binds VEGF
Term
name a monoclonal Ab that binds VEGF
Definition
bevacizumab
Term
adverse effects of bevacizumab?
Definition
HTN, arterial thrombosis, impaired wound healing, GI perforation, proteinuria
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