Antineoplastics Flashcards
During what phase of the cell cycle are antimetabolites most effective?
S-phase
What event can increase the resistance to methotrexate?
gene duplications of DHFR
decreased affinity of DHFR for methotrexate
What drug is a prodrug 5FU? Why is this drug used?
capectibane
increased oral availability
What enzyme ACTIVATES cytarabine?
Deoxycytidine Kinase
What enzyme does cytarabine inhibit?
DNA polymerase
What cancer is most commonly treated with cytarabine?
AML
What enzyme does ara-C inhibit?
DNA polymerase
What drug causes cerebellar syndrome? Why?
cytarabine
cytadine deaminase levels are low in CNS
What enzyme inactivates cytarabine?
cytidine deaminase
What are the two enzymatic mechanisms by which resistance to cytarabine develops?
loss of deoxycytidine kinase
increase cytidine deaminase
What is gemcitabine an analogue of?
Difluorodeoxycytidine
What enzyme activates gemcitabine?
Deoxycytidine Kinase
What enzyme does deoxycytidine kinase inactivate?
Ribonucleotide Reductase
What are the two mechanisms by which tumor cells can increase resistance to gemcitabine?
decreased expression of deoxycytidine kinase
increase expression of deoxycytidine
What enzyme activates 6-MP and 6-TG?
HGPRTase
What is 6-MP converted to?
thio-IMP
What is 6-TG converted to?
thio-GMP
What can thio-IMP be converted into?
thio-GMP
What two products does IMP get converted into?
AMP and GMP
What can thio-GMP be converted into?
thio-dGTP
What is the main side effect of 6-MP and 6-TG?
myelosuppression
How do cells become resistant to 6-MP and 6-TG?
mutations in HGPRTase
Is fludarabine a purine or pyrimidine analogue?
purine
What enzyme activates fludarabine?
Deoxycytidine kinase
What two enzymes does fludarabine inhibit?
DNA polymerase and RNR
What cancer is most often treated with fludarabine?
CLL
What is the mechanism by which fludarabine resistance can develop?
decreased activity of deoxycytidine kinase
Is cladribine a purine or pyrimidine analogue?
purine
What enzyme activates cladrabine?
deoxycytidine kinase
What enzyme is inhibited by cladrabine ?
RNR
What disease is most often treated with cladrabine?
hairy cell leukemia
What are the two mechanisms by which a cell can become resistance to cladribine?
decreased activity of deoxycytidine kinase
increased expression of RNR
What is the most common site for alkylating agents to function?
Guanine N7
What disease often presents after treatment with an alkylating agent?
leukemia
What type of drug is Mechlorethamine?
alkylating agent
What type of drug is cyclophosphamide?
alkylating agent
What is the main side effect of cyclophosphamide?
hemorrhagic cystitis
What drug is used to treat the side effects of cyclophosphamide? What is the MOA of this drug?
Mesna
scavenges acroleid
What is the MOA of carmustine? What type of drug family does carmustine fall into?
alkylating agent
nitrosurea
What type of cancer is most often treated with carmustine?
brain tumors
What are the three non-classical alkylating agents ?
carboplatin
cisplatin
oxaliplatin
What are the three main adverse effects of cisplatin?
nephrotoxicity
peripheral neuropathy
ototoxicity
What is the main difference between cisplatin and carboplatin?
carboplatin does not cause nephrotoxicity or neuropathy
What is used to mitigate the deleterious effects of cisplatin?
co-administration with IV saline
What is the MOA of vinblastine?
prevents formation of microtubules
What is the MOA of vincristine?
prevents formation of microtubules
What is the main side effect of cytarabine?
pancytopenia
What is the main side effect of Carboplatin?
myelosuppression
What is the main side effect of vinblastine?
myelosuppression (BLASTs bone marrow)
What is the main side effect of vincristine?
neurotoxicity
What subunit of microtubules does paclitaxel bind? What does this prevent?
β-tubulin
disassembly of microtubules
What are the two main side effects of paclitaxel?
PERIPHERAL NEUROPATHY and myelosuppression
What drug is used to ameliorate the myelosuppressive side effects of paclitaxel? What is the MOA of this drug?
Filgrastim
acts as G-CSF
What drug has the identical MOA of paclitaxel?
Docetaxel
Paclitaxel and docetaxel requires the pretreatment with what two drugs? Why?
Dexamethosone or anti-histamine
prevent hypersensitivity
Topoisomerase I is inhibited by what two drugs? What phase of the cell cycle do these two drugs work?
irinotecan and topotecan
S-phase
What enzyme does etoposide inhibit?
topoisomerase II
What are the three MOAs of doxorubicin?
intercalates DNA
inhibit DNA polymerase
inhibits topoisomerase II
What is the main adverse effect of doxorubicin?
cardiomyopathy
What drug functions similar to doxorubicin but has a lower liklihood of developing cardiomyopathy?
Epirubicin
Iron and copper can be chelated by what drug?
Bleomycin
What is the MOA of bleomycin?
causes single and double stranded DNA breaks
What is the main side effect of bleomycin?
pulmonary fibrosis
What type of cancer would prednisone be useful for? Why?
lymphocytic leukemias
causes apoptosis of lymphocytes
What cancer is dexamethasone used to treat?
multiple myeloma
Other than endometrial issues, what can tamoxifen cause?
thromboembolism
How does a cell develop a resistance to tamoxifen?
decreased affintity for the estrogen receptor
What is the MOA of anastrazole? What patient group?
aromatase inhibitor
post-menopausal women
What specific type of cancer is anastrazole used to treat?
estrogen sensitive breast cancer
What two drugs are androgen receptor antagonists?
Flutamide and bicalutamide
What specific type of cancer are flutamide and bicalutamide used to treat?
prostate
What two drugs affect GnRH release? Are they agonists or antagonists?
Leuprolide and Goserelin
Agonists
Leuprolide and Goserelin are used to decrease the secretion of what? How do they do this?
LH and FSH
desensitizing GnRH receptors
What is the GnRH antagonist?
Degarelix
What is another name for trastuzumab?
Herceptin
What family does HER2/Neu belong?
EGFR
What is the main side effect of trastuzumab?
cardiotoxicity
What type of antibody is Cetuximab? What does Cetuximab target? What cancer?
monoclonal
EGFR
colorectal
How does resistance to cetuximab develop?
mutations in Ras signaling
What three proteins can imatinib inhibit?
BCR-ABL
c-Kit
PDGF
How does resistance against imatinib develop?
point mutations in ABL
What receptor is inhibited by Erlotinib? What is the MOA of erlotinib?
EGFR inhibitor
prevent ATP from binding
What rxn does asparaginase catalyze?
asparagine into aspartate
What cancer is most often treated with asparaginase?
ALL
What is the primary side effect of asparaginase?
allergic rxn
What is the MOA of bortezomib? The txn of what gene can be inhibited by Bortezomib?
inhibitor of proteasome
NFKB
What is the mechanism by which bortezomib can inhibit neoplasia?
inhibition of apoptosis during hypoxic conditions
What specific important protein can Bortezemib inhibit the activity of ?
p53
What is the most common side effect of bortezemib?
peripheral neuropathy
Temsirolimus is an analogue of what drug? What complex is inhibited? What does this lead to?
rapamycin
mTOR
apoptosis
What cancer is temsirolimus currently in approval for treatment of?
renal cell carcinoma
What are the two specific toxicities of methotrexate?
interstitial pneumonitis
nephrotoxic
Cytarabine is an incredibly important drug in treating what cancer?
AML
When cell cycle phase is cytarabine most effective ?
S-phase
What is the primary mode of resistance in AML?
loss of deoxycytidine kinase activity
What enzyme does gemcitabine inhibit?
ribonucleotide reductase
What is the main treatment of ALL?
6-MU/Azathioprine
What organ is acrolein most toxic to?
bladder
What is the important functional group of mesna?
sulfhydryl
What molecule can a cell produce in order to increase resistance to an alkylating agent?
glutathione
What enzyme can cells increase to provide resistance against alkylting agents? What is the MOA of this enzyme?
MGMT
quickly removes alkyl group from DNA
What transporter is used to get platinum containing drugs into the cell?
copper transporter
What is a shared toxicity between cisplatin and carboplatin?
anaphylaxis reactions
What cancer is procarbazine used to treat?
Hodgkin’s lymphoma
What three cancers can dacarbazine treat?
HL, Melanoma, Sarcoma
What two cancers can temozolomide treat?
gliablastoma and metastatic melanoma
What drug is often co-administered with doxorubicin? What is the MOA of this drug?
Dexrazoxane
to chelate iron
What cell cycle phase is interrupted by bleomycin?
G2
What is a notable characteristic about bleomycin concerning its administration with other drugs?
minimally myelosuppressive
What family of drugs are used to reduce intracranial pressure?
glucocorticoids
What is the most common side effect of bevacizumab?
hypertension
Which two receptors does Lapatinib inhibit? What is the MOA of this drug?
EGFR and HER-2
inhibits tyrosine kinase activity of HER2 and EGFR
Does imatinib inhibit BCR or ABL? By what mechanism?
ABL
competitive inhibitor of ABL ATP binding site
What cancer is asparaginase used to treat? Why?
ALL
tumor cells cant produce enough asparagine
What cancer is bortezemib used to treat?
refractory multiple myeloma
What drug is used in combat the negative effects of methotrexate? What is the MOA of this drug?
Leucovorin
folinic acid
Methotrexate causes can kill which two types of cell?
bone marrow and intestinal epithelial
How does hemorrhagic cystitis manifest?
blood in urine
What is the most severe side effect of carmustine?
myelosuppression
What three reasons is carbiplatin used in the place of cisplatin?
decrease ototoxicity
decreased nephropathy
decreased peripheral neuropathy
What drug is used to mitigate the effects of paclitaxel? Why?
filgastrim
acts as GCSF
What is another side effect of paclitaxel, other than myelosuppression and peripheral neuropathy?
Hypersensitivity rxn
What are the two main side effects of irinotecan and topotecan?
myelosuppression and diarrhea
Which antineoplastic can chelate iron and copper ?
bleomycin
What is the MOA for how Degarelix is used to treat prostate cancer?
decreases FSH and LH secretion from anterior pituitary
What drug is trastuzumab often used in combination with?
paclitaxel
What type of symptoms do all monoclonal therapies produce?
B-cell symptoms
What is the common side effect of avastin?
HTN
Which component of BCR-ABL fusion has the kinase activity?
ABL
How do cells develop resistance against imatinib?
point mutations in ABL
Erlotinib is used to treat which type of cancer?
metastatic non-small cell lung carcinoma
Bortezomib is used to treat what cancer?
multiple myeloma
Does methotrexate inhibit DNA or RNA or synthesis of both?
both
Does methotrexate inhibit purine or pyrimidie or synthesis of both?
both
What drug is methotrexate often used in combination with?
Dactinomycin
What enzyme does 5-FU inhibit?
thymidylate synthase
What is 5-FU metabolized into?
FdUMP
Does 5-FU cause damage to DNA or RNA or both?
both
Which phase of the cell cycle is cytarabine effective in?
S-phase
What is 6-MP converted into?
thio-IMP
What is 6-TG converted into?
thio-GMP
Thiopurine methyltransferase selectively inhibits which anti-neoplastic? What is the severe effect in individuals who have mutations in this enzyme?
6-MP
life-threatening bone marrow suppression
Does thio-IMP inhibit the synthesis or salvage or both of purines?
both
During what cell cycles are alkylating agents cytotoxic?
all cell cycles
What is the main side effect of all alkylating agents?
myelosuppression
What are the two mechanisms of resistance for all alkylating agents?
glutathione
MGMT (methylguanosine-methyl transferase)
What nucleophile do non-classical alkylating agents target?
Guanine N7
How do non-classical alkylating agents get into the cell?
copper transporter
What electrolyte can cisplatin disturb?
magnesium
Which two alkylating agent can cause hypersensitivity rxns?
Cisplatin and carboplatin
What cancer is treated with procarbazine?
HL
What two cancers are treated with dacarbazine?
melanoma and sarcoma
What cell cycle phase does paclitaxel arrest cells in?
mitosis
Lapitinib is a monoclonal antibody against which two receptors? Which cancer is lapitinab used to treat?
EGFR and HER2
refractory breast
What are the two mechanisms by which a cancer may develop resistance to erlotinib?
mutation in EGFR
amplification of MET oncogene
Tamoxifen can increase the risk for what cancer?
endometrial
Flutamide and bicalutamide prevent what agonist from binding the androgen receptor?
dihydrotestosterone
Which anti-neoplastics can cause blister and damage veins?
alkylating agents
What is the main use of bevucizimab?
colorectal cancer
