Antineoplastic agents II Flashcards by tcarlso 3

What are the three major ways in which tumors become resistant to cytarabine?

Downregulate transporter
Downregulate deoxycyidine
Upregulate cytidine deaminase

How well did you know this?

Not at all

Perfectly

What is the MOA of gemcitabine?

difluorodeoxycytidine is converted by deoxycitidine kinase, and is incoroprated into DNA, and inhibits ribonucleotide reductase

How well did you know this?

Not at all

Perfectly

What are the two MOA of resistance to gemcitabine?

Reduced deoxycytidine kinase

Increased production of deoxycytidine

How well did you know this?

Not at all

Perfectly

What is the MOA of 6-mercaptopurine and 6-thioguanine?

HGPRT enzyme converts them to thio IMP or thioGMP, inhibiting RNA/DNA synthesis

How well did you know this?

Not at all

Perfectly

What is the enzyme that degrades 6MP and 6TG? What is significant about this enzyme?

Thiopurine methyltransferase (TPMT)

Some in the population do not have this, thus have much higher toxicity levels

How well did you know this?

Not at all

Perfectly

What are the cancers that 6MP and 6TP treat?

Acute myelogenous leukemia

Acute lymphocytic leukemia

How well did you know this?

Not at all

Perfectly

What are the adverse effects of 6MP and 6TP?

Bone marrow suppression

How well did you know this?

Not at all

Perfectly

What is the MOA of resistance to 6MP and 6TP?

Deficiency in HGPRT

How well did you know this?

Not at all

Perfectly

What is the MOA of fludarabine?

Deoxycitidine kinase activates it in cells, and it is incorporated into DNA/RNA, and inhibiting DNA polymerase and ribonucleotide reductase

How well did you know this?

Not at all

Perfectly

What are the cancers the fludarabine is used to treat?

chronic lymphocytic leukemia

How well did you know this?

Not at all

Perfectly

What is the MOA of resistance to fludarabine and cladribine?

Decreased deoxycitidine kinase

How well did you know this?

Not at all

Perfectly

What is the MOA of cladribine?

Deoxycitidine kinase activates it in cells, and it is incorporated into DNA/RNA, and inhibiting DNA polymerase and ribonucleotide reductase

How well did you know this?

Not at all

Perfectly

What is the enzyme that activates fludarabine and cladribine?

deoxycitidine kinase

How well did you know this?

Not at all

Perfectly

Why do we have to give purine/pyrimidine analogs in an inactive form?

Otherwise will not enter the cell

How well did you know this?

Not at all

Perfectly

What is the cancer that cladribine?

Hair cell leukemia

How well did you know this?

Not at all

Perfectly

What is the general MOA of alkylating agents?

intrastrand linking and cross linking

How well did you know this?

Not at all

Perfectly

When in the cell cycle are alkylating agents effective?

All stages

How well did you know this?

Not at all

Perfectly

What are the two nitrogen mustards that are used as alkylating agents?

Mechlorethamine

Cyclophosphamide

How well did you know this?

Not at all

Perfectly

What cancer is mechlorethamine used to treat?

Hodgkin’s lymphoma

How well did you know this?

Not at all

Perfectly

What are the unique adverse effects of cyclophosphamide? MOA?

Hemorrhagic cystitis

converted to acrolein, which is toxic to the baldder cells

How well did you know this?

Not at all

Perfectly

What is the drug that you coadminister with cyclophosphamide to reduce the chances of developing hemorrhagic cystitis? MOA?

Mesna

Inactivates acrolein

How well did you know this?

Not at all

Perfectly

What is the MOA of carmustine?

Alkylating agent

How well did you know this?

Not at all

Perfectly

What is carmustine used to treat?

Brain ca

How well did you know this?

Not at all

Perfectly

What are the adverse effects of alkylating agents?

Mutagenic, teratogenic, and myelosuppressive

How well did you know this?

Not at all

Perfectly

What cancer develops with the use of alkylating agents?

Leukemia

Besides the usual routes of resistance to drugs, how do tumor resist alkylating agents?

Inactivation by glutathione Increased expression of 06-methylguanine-DNA methyltransferase (MGMT)

What is the MOA of 06-methylguanine-DNA methyltransferase (MGMT)?

Removes the alkyl groups on DNA that were added by alkylating agents

What is the MOA of the platinum compunds?

Cause cross-linking of DNA

What are the three platinum compounds that act like alkylating agents?

Cisplatin Carboplatin Oxaliplatin

Platinum compounds increase the risk for what cancer?

Leukemia

Which causes less n/v: cisplatin or carboplatin?

Carboplatin

What are the adverse effects of cisplatin?

tinnitus Nephrotoxicity peripheral neuropathy

What is the MOA of procarbazine? What is it used to treat? | board

Non-classical alkylating agent Hodgkins

What is the MOA of dacarbazine? | board

Non-classical alkylating agent | melanoima/sarcoma

What is the MOA of temozolomide? | board

Non-classical alkylating agent | Glioblastomas

What is the dynamic instability of microtubules?

Constant breakdown and restructuring

What is the MOA of vinblasine and vincristine?

Causes mitotic arrest by preventing formation of microtubules

Which drug has neurotoxicity: vinblastine or vincristine?

Vincristine

What is the MOA of paclitaxel?

Binds to beta tubulin of microtubules, and prevent the disassembly

What is the MOA of docetaxel?

Binds to beta tubulin of microtubules, and prevent the disassembly

What are the adverse effects of paclitaxel?

Myelosuppression and peripheral neuropathy

What are the adverse effects of docetaxel?

Periperhal neuropathy

What is the drug that is used with paclitaxel, to reduce myelosuppression?

Filgrastim

What do topoisomerases do in DNA replication?

Cut DNA, unwind, and repair the cut

What are the two topoisomerase inhibitors?

Irinotecan | Topotecan

What is the MOA of etoposide?

Class IITopoisomerase inhibitor

What is the MOA of doxorubin?

Abx that intercalates with DNA, leading to inhibition of DNA polymerase

What is the significant adverse effect of doxorubin?

cardiomyopathy via free radical formation

What is the drug that is administered with doxorubicin that mitigates the cardiotoxicity?

Dexrazoxane (Fe chelator)

What is the MOA of bleomycin?

Small glycopeptide antibiotic that chelates iron and copper and binds to DNA and causes single and double strand breaks.

What are the adverse effects of bleomycin?

Pulmonary toxicity

Which of the antineoplastic are minimally myelosuppressive (3)?

Bleomycin Vincritine Methotrexate

What is the MOA of glucocorticoids in the treatment of cancer?

Inhibit lymphocyte proliferation

What is the MOA of dexamethasone?

Glucocorticoid

What is the MOA of tamoxifen?

Selective estrogen receptor modulator (competes for estrogen receptor)

What are the adverse effects of tamoxifen?

Increased risk of endometrial CA Increased risk of thromboembolism

What are the resistance mechanisms of tamoxifen?

Estrogen receptor changes cause a reduced affinity with tamoxifen.

What is the MOA of anastrozole?

Aromatase inhibitor (recall that aromatase synthesizes estrogen from androgens in peripheral tissue)

What is anastrozole used for?

Treatment of breast cancers

What are the two androgen receptor inhibitors? What are thy used to treat?

Flutamide Bicalutamide Prostate CA

What is the MOA of flutamide?

androgen receptor inhibitor

What is the MOA of bicalutamide?

androgen receptor inhibitor

What is the MOA of leuprolide?

GnRH agonist

What is the MOA of goserelin?

GnRH agonist

How do the GnRH agonists work?

Cause a desensitization of the GnRH receptors, which reduces the secretion of both LH and FSH from the anterior pituitary

What is the MOA of degarelix

GnRH antagonist, which decreases LH and FSH production

What is the MOA of trastuzumab?

Binds to estrogen growth signal receptor (HER2), and inhibits it

What is the MOA of cetuximab?

Monoclonal antibody against EGFR

What are the adverse effects of trastuzumab?

Cardiac toxicity if combined

What cancer does cetuximab treat?

EGRF expressing Colorectal cancers

What is the mechanism of resistance to cetuximab?

Acquiring activating mutations in RAS

What is the general MOA of monoclonal antibodies in treating CA?

Inhibit growth signals | Cause immune mediated destruction

What is the MOA of bevacizumab?

Ab against VEGF, inhibiting angiogenesis

What is the cancer that bevacizumab is used to treat?

clear cell renal cancer

What are the adverse effects of bevacizumab?

significant blood vessel injury and reduces wound healing

What is the MOA of lapatinib?

Inhibits EGFR and HER-2 kinase activity

What is the MOA of erlotinib?

EGRF inhibitor | ATP competitive inhibitor

How does the EGRF molecule work?

Y kinase that is activated extracellularly, when epidermal growth factor binds, and activates the MAP kinase cascade

What is the therapeutic use of erlotinib?

Nonsmall cell lung carcinoma if pts have mutation in gene

How does resistance come about with erlotinib?

Secondary mutation in EGRF or amplification of MET oncogene

What is the MOA of imantinib (gleevec)?

Binds to ABL portion of the philidelphia chromosome, and prevents kinase from binding its substrate/phosphate donor

What is imantinib used to treat?

Chronic myelogenous leukemia

What is the mechanism of resistance to imantinib?

Point mutation BCR-ABL protein to not bind imantinib anymore

What is the MOA of asparaginase?

Lowers blood [asparagine], which kills tumor cells since they cannot synthesize sufficient asparagine

What is asparaginase used to treat?

acute lymphoblastic leukemia

What are the adverse effects of aparaginase?

anaphylaxis

What is the MOA of bortezomib? (2)

Inhibits proteasome, which increases p53

What cancer does bortezomib treat?

multiple myeloma

What is the main adverse effect with bortezomib?

Peripheral neuropathy

What is the MOA of temsirolimus?

inhibition of mTOR complex, which promotes cell cycle

What cancer is temsirolimus used to treat?

renal cell carcinoma

What is the mechanism of resistance against temsirolimus?

mTOR 2 increased