Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
64 Cards in this Set
- Front
- Back
Pat tx w chemo for Hodgkins develops symptoms of schizophrenia - which drug? – vincristine, nitrogen mustard, prednisone, combination or another drug?
|
A; prednisone = CNS toxicity = psychosis
vincristine = neurotoxicity (areflexia, peripheral neuritis) limits usefulness nitrogen mustards = alkylate DNA = M2C2 = mechlorethamine, melphalan, cyclophosphamide, chlorambucil |
|
Cancer cells lacking hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) are resistant to ?
|
6-mercaptopurine and 6-thioguanine The enzyme HGPRTase converts 6-MP and 6-TG to a nucleotide form which inhibits purine synthesis and thus blocks DNA/RNA synthesis
|
|
Cyclophosphamide used to treat non-Hodgkins lymphoma, breast and ovarian carcinomas. MOA:
|
activated by CYP450 to a metabolite which covalently x-links DNA strands at guanine N-7
|
|
Cyclophosphamide used to treat non-Hodgkins lymphoma, breast and ovarian carcinomas. S/E:
|
causes sterile hemorrhagic cystitis; alkylating agents like cyclophosphamide can cause myelogenous (granulocytic) leukemia
|
|
Patient to be treated w chemo w cyclophosphamide. Patient is receiving a drug for gout. Which gout drug would increase the toxicity of cyclophosphamide?
|
allopurinol prolongs the half-life of cyclophosphamide, how = unknown ?
|
|
Neoplastic drug interaction with allopurinol
|
a. alluopurinol inhibits xanthine oxidase to prevent the formation of uric acid)
b. allopurinol often used after tx of hematologic cancers to prevent hyperuricemia after tumor cell lysis c. allopurinol inhibits the metabolism of 6-mercaptopurine (6-MP) by xanthine oxidase, so need to reduce dose of 6-MP to 25% of normal dose in patients on allopurinol d. Need to decrease dose of immunosuppressive drug azathioprine by 25% of normal when given to a patient taking allopurinol because azathioprine is metabolized to 6-MP |
|
Drugs which interfere w microtubule function
|
vincristine, vinblastine, paclitaxel (taxol), colchicine, griseofulvin and mebendazole
|
|
vincristine MOA
|
binds to tubulin and blocks the ability of tubulin to polymerize into microtubule = mitotic arrest in metaphase
|
|
paclitaxel MOA
|
binds to microtubules of mitotic spindle to hyperstabilize them so that they cannot break down in anaphase, get mitotic arrest
|
|
paclitaxel med use
|
used to treat ovarial and breast cancer
|
|
dactinomycin (actinomycin D) MOA:
|
binds tightly to double-stranded DNA between G-C pairs to inhibit all forms of DNA-dependent RNA synthesis, esp. mRNA synthesis
|
|
dactinomycin (actinomycin D) med use:
|
used for the tx of Wilm’s tumor
|
|
doxorubicin and daunorubicin MOA:
|
intercalation into DNA - inhibits synthesis of DNA/RNA
|
|
doxorubicin and daunorubicin toxicity:
|
froms free radicals and oxygen radicals causing cardiac toxicity via membrane damage
|
|
methotrexate MOA:
|
a folic acid antagonist which binds to DHF reductase, interferes w synthesis of thymidylate, purine nucleotides and the AA’s serine and methionine = inhibition of synthesis of DNA, RNA and proteins
|
|
methotrexate med use:
|
to treat leukemias and sarcomas
|
|
methotrexate resistance by what mechanisms:
|
- decreased drug transport
- altered DHFR - increased activity of DHFR - decreased polyglutamate formation |
|
methotrexate S/E:
|
major bone marrow depression
|
|
A patient tx w methotrexate develops bone marrow depression. How to tx?
|
"leucovorin rescue” = tx w leucovorin (folinic acid) to reverse bone marrow depression. Normal cells can take up leucovorin, but tumor cells cannot, so
leucovorin rescues normal cells but not tumor cells |
|
5-fluorouracil (5-FU) MOA
|
inhibition of DNA synthesis: 5-FU converted to FdUMP which inhibits thymidylate synthetase. No dTMP formed, so no thymidine nucleotides formed = “thymidineless death”
b. inhibition of RNA processing c. no leucovorin rescue possible |
|
5-fluorouracil (5-FU) med use:
|
used to treat colon cancer (combined with levamisole)
|
|
pat on chemo has cough w crackles, X-ray shows diffuse basilar infiltrates, drug ?
|
bleomycin
|
|
bleomycin MOA:
|
fragmentation of DNA via formation of activated oxygen species (free radicals), cells accumulate in G2 w chromatid breaks, gaps, fragments and translocations
|
|
bleomycin S/E:
|
blasts the lungs
|
|
Drug w antiestrogenic effects for tx of breast cancer = ?
|
tamoxifen
|
|
carmustine, lomustine
|
nitrosoureas
|
|
nitrosoureas med use
|
to treat brain tumors (crosses BBB)
|
|
nitrosoureas MOA:
|
cross link DNA via alkylation; requires bioactivation
|
|
Which type of receptors must be present for the tx a breast cancer w the GnRH analogs leuprolide and goserelin?
|
estrogen receptors in the tumor tissue MOA of GnRH analogs = act on pituitary to inhibit the release of LH and FSH, decreased LH decreases estrogen synthesis by ovaries
|
|
cisplatin med use:
|
to treat testicular and lung carcinomas
|
|
cisplatin MOA:
|
forms intra- and interstrand cross links at N7 of guanine via hydroylsis of chloride groups = inhibits DNA replication and transcription; replacement of chloride with water forms the active drug
|
|
cisplatin S/E:
|
nephrotoxic which is decreased by Cl- diuresis because Cl- stabilizes the
platin complex: renal toxicity causes loss of Mg++, Ca++, K+ and phosphate |
|
prednisone (glucocorticoid) neoplastic use:
|
used to treat chronic lymphocytic leukemia, Hodgkin’s lymphoma
|
|
prednisone (glucocorticoid) MOA for neoplasms:
|
apotosis in non-dividing cells
|
|
radiation and alkylating agents MOA
|
increase tumor cell death by increasing dose antimetabolites
- increase tumor cell death by increasing exposure time, not the dose |
|
alkylating agents toxicity
|
moderate bone marrow depression, large doses cause severe depression with leukopenia, thrombocytopenia and bleeding
|
|
busulfan toxicity
|
skin pigmentation, pulmonary fibrosis, adrenal insufficiency
|
|
cyclophosphamide toxicity
|
hemorrhagic cystitis
|
|
cisplatin toxicity
|
renal damage, acoustic nerve dysfunction
|
|
procarbazine toxicity
|
CNS depression
|
|
glucorticoids = prednisone toxicity
|
immunosuppression, adrenal suppression, psychosis
|
|
cytarabine toxicity
|
megaloblastosis
|
|
5-fluorouracil toxicity
|
oral and GI ulceration
|
|
mercaptopurine (6-MP) toxicity
|
toxicity potentiated by allopurinol
|
|
methotrexate toxicity
|
oral and GI ulceration, bone marrow depression
|
|
bleomycin toxicity
|
pulmonary fibrosis
|
|
dactinomycin toxicity
|
bone marrow suppression
|
|
doxorubicin toxicity
|
cardiac toxicity, bone marrow depression, red urine (not hematuria)
|
|
etoposide toxicity
|
bone marrow depression
|
|
vincristine toxicity
|
areflexia, peripheral neuritis, muscle weakness, paralytic ileus, alopecia
|
|
vinblastine toxicity
|
loss of reflexes, bone marrow depression, alopecia
|
|
paclitaxel (taxol) toxicity
|
bone marrow depression, peripheral neuropathy
|
|
hydroxyurea toxicity
|
bone marrow depression
|
|
tamoxifen toxicity
|
increased risk of endometrial cancer, menopausal symptoms
|
|
What is the S-phase-specific drug that inhibits DNA polymerase after metabolic activation?
|
cytarabine (cytosine arabinoside)
|
|
cytarabine (cytosine arabinoside) MOA:
|
originally thought to inhibit DNA polymerase, but now know to inhibit DNA synthesis by inhibiting chain elongation when AraCTP is incorporated into the growing DNA chain
deoxycytidine kinase is the enzyme that converts it to AraCMP |
|
antimetabolites inhibit in what cell cycle phae:
|
S phase
|
|
cell cycle non-specific
|
alkylating agents = mechlorethamine, melphalan, cyclophosphamide, chlorambucil, busulfan, cisplatin,
dacarbazine procarbazine nitrosoureas = carmustine, lomustine glucocorticoids dactinimycin daunorubicin doxorubicin plicamycin |
|
cell cycle specfic
|
antimetabolites
cytarabine 5-fluorouracil 6-mercaptopurine (6-MP) 6-thioguanine (6-TP) methotrexate hydroxyurea bleomycin etoposide vincristine vinblastine paclitaxel (taxol) |
|
S phase inhibitors
|
hydroxurea - inhibits ribonucleotide reductase
5-fluorouracil - inhibits thymidylate synthetase 6-MP, 6-TP - inhibit purine synthesis methotrexate - inhibits DHF reductase cytarabine - inhibits DNA chain elongation |
|
inhibitors of synthesis of molecules needed for mitosis work at which cell cycle phase?
|
G2 phase
|
|
G2 phase inhibitors
|
bleomycin – fragmentation of DNA, cells accumulate in G2
etoposide stabilizes the bond between Topo II and DNA; Topo II is inhibited so double-stranded DNA breaks remain; DNA is degraded; blocks in late S-G2 (Topoisomerases cut 1- or 2-stranded DNA to allow the strand to unwind; TOP 1 and TOP 2 are necessary for DNA replication and RNA transcription; TOP 2 is needed for the completion of mitosis) |
|
drugs interfering in M phase
|
paclitaxel (taxol): enhances polymerization of tubulin, promotes microtubule assembly and stabilizes microtubules against depolymerization; causes mitotic arrest because anaphase cannot occur
vincristine and vinblastine: bind to tubulin and prevent the assembly of microtubules; |
|
Non-phase specific drugs
|
a. can work at any step in the cell cycle, including Go
b. cells are more sensitive in late G1 and S because polynucleotides are more susceptible to alkylation in the unpaired state than in the helical form c. toxicity usually expressed when cells enter S phase and progression through cell cycle is blocked |