Reading...
Play button
Play button
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;
118 Cards in this Set
- Front
- Back
|
log kill hypothesis
|
cancer drugs follow first order kinetics and kill a fixed PERCENTAGE of tumor cells, not a fixed number
|
|
|
general side effects of cancer chemotherapeutics (7)
|
1. bone marrow toxicity
2. impaired wound healing 3. loss of hair 4. damage to GI epithelium 5. depression of growth 6. sterility 7. teratogenicity |
|
|
what are the most commonly used anti-cancer drugs?
|
alkylating agents
|
|
|
mechanism of action of alkylating agents
|
form covalent bonds w/ N7 of guanine (nucleophillic)
|
|
|
general side effects of alkylating agents (4)
|
1. bone marrow depression
2. GI disturbances 3. depression of gametogenesis in men w/ prolonged use 4. increased risk of acute non-lymphocytic leukemia |
|
|
cyclophosphamide
|
nitrogen mustard
--> metabolized in liver into phosphoramide mustard and acrolein |
|
|
clinical uses of cyclophosphamide (4)
|
1. non Hodgkin lymphome
2. ovarian cancer 3. breast cancer 4. neuroblastoma |
|
|
toxic effects of cyclophosphamide (3)
|
1. N/V
2. bone marrow depression 3. hemorrhagic cystitis - caused by acrolein |
|
|
how can you prevent acrolein toxicity? (2)
|
1. increased fluid intake
2. increased diuresis w/ mannitol and compounds such as sulfhydryl donor i.e. N acetylcysteine, mesna |
|
|
what are the nitrogen mustards? (7)
|
cyclophosphamide
ifosphamide estramustine melphalan chlorambucil mechlorethamine |
|
|
ifosphamide
|
isomer of cyclophosphamide
but is more TOXIC and IV only |
|
|
trophosphamide
|
nitrogen mustard used orally in palliative treatment of cancers such as : testicular tumors, sarcomas, lung, breast and ovarian cancers
|
|
|
estramustine
|
combo of chlormethine (mustine) + estrogen
|
|
|
clinical use of estramustine
|
Tx. of prostate cancer
|
|
|
melphalan
|
nitrogen mustard
given orally for treatment of multiple myeloma |
|
|
chlorambucil
|
nitrogen mustard
used for tx. of CLL, primary macroglobulinemia |
|
|
mechlorethamine - mechanism of action
|
nitrogen mustard
--> taken up by choline uptake system and alkylates N7 of guanine |
|
|
MOPP regimen
|
TX of Hodgkins disease
M- mechlorethamine O - oncovine P - prednisone P- procarbazine |
|
|
adverse effects of mechlorethamine (4)
|
1. toxic when extravasated (IV)
2. severe vomiting 3. severe bone marrow depression 4. immunosuppression |
|
|
what are the nitrosureas? (3)
|
lomustine
carmustine semustine |
|
|
streptozocin
|
natural sugar containing nitrosurea
--> used in insulin secreting cancer of pancreas |
|
|
clinical use of nitrosureas?
|
lipid soluble -> cross BBB
therefore, can be used to Tx. of tumors of brain and meninges |
|
|
adverse effects of nitrosureas
|
1. delayed hematopoietic depression
2. bone marrow aplasia 3. renal toxicity |
|
|
busulfan
|
selective effect on bone marrow --> depresses formation of granulocytes/platelets (low dose) and RBCs (high dose)
|
|
|
busulfan used to treat...
|
chronic granulocytic anemia
|
|
|
altretamine
|
alkylating agent used in the treatment of refractory ovarian cancer (salvage therapy)
|
|
|
cisplatin
|
alkylating agents (platinum compound)
|
|
|
cisplatin - mechanism
|
Cl- dissociates leaving a reactive complex which causes intrastrand cross-linking --> local denaturation of DNA
|
|
|
clinical uses of cisplatin
|
Tx. of solid tumors of:
testes ovary bladder lung |
|
|
adverse effects of cisplatin (5)
|
1. cumulative nephrotoxicity
2. nausea/vomiting - severe 3. tinnitus/hearing loss 4. peripheral neuropathies 5. anaphylactic reactions |
|
|
amifostine
|
agent used in conjunction w/ chemotherapy to:
- reduce neutropenia-related fever/infection - reduce cumulative nephrotoxicity - reduce incidence of xerostomia |
|
|
carboplatin
|
platinum containing compound that is a derivative of cisplatin
--> inhibits DNA and RNA synthesis by binding to proteins and SH groups |
|
|
G2 phase specific drugs
|
bleomycin
|
|
|
S phase specific drugs (7)
|
cytarabine
6-mercaptopurine 6-thioguanine methotrexate hydroxyurea etoposide 5-FU |
|
|
M phase specific drugs (3)
|
vinblastine
vincristine paclitaxel |
|
|
G0 phase specific drugs (4)
|
alkylating agents
anti-tumor antibiotics nitrosureas cisplatin |
|
|
amifostine
|
agent used in conjunction w/ chemotherapy to:
- reduce neutropenia-related fever/infection - reduce cumulative nephrotoxicity - reduce incidence of xerostomia |
|
|
carboplatin
|
platinum containing compound that is a derivative of cisplatin
--> inhibits DNA and RNA synthesis by binding to proteins and SH groups |
|
|
adverse effects of carboplatin
|
LESS nephrotoxicity/neurotoxicity than cisplatin
MORE myelotoxicity |
|
|
dacarbazine
|
alkylating agent that is bioactivated to active cpd in the liver
|
|
|
G2 phase specific drugs
|
bleomycin
|
|
|
S phase specific drugs (7)
|
cytarabine
6-mercaptopurine 6-thioguanine methotrexate hydroxyurea etoposide 5-FU |
|
|
adverse effects of dacarbazine (2)
|
1. myelotoxicity
2. severe nause/vomiting |
|
|
M phase specific drugs (3)
|
vinblastine
vincristine paclitaxel |
|
|
Clinical Uses of Dacarbazine (3)
|
1. single agent in metastatic melanoma
2. ABVD regimen - hodgkins 3. MAID regimen - soft tissue sarcoma |
|
|
G0 phase specific drugs (4)
|
alkylating agents
anti-tumor antibiotics nitrosureas cisplatin |
|
|
adverse effects of carboplatin
|
LESS nephrotoxicity/neurotoxicity than cisplatin
MORE myelotoxicity |
|
|
dacarbazine
|
alkylating agent that is bioactivated to active cpd in the liver
|
|
|
adverse effects of dacarbazine (2)
|
1. myelotoxicity
2. severe nause/vomiting |
|
|
Clinical Uses of Dacarbazine (3)
|
1. single agent in metastatic melanoma
2. ABVD regimen - hodgkins 3. MAID regimen - soft tissue sarcoma |
|
|
temozolimide
|
alkylating agent used to tx. malignant glioma
|
|
|
procarbazine - mechanism (2)
|
alkylating agent - inhibits RNA and DNA synthesis
- formation of H2O2, formaldehyde and free ROS |
|
|
adverse effects of procarbazine (5)
|
1. NVD
2. myelosuppresion 3. psychic disturbances 4. disulfuram-reaction 5. leukemogenic |
|
|
procarbazine is used for treatment of ...
|
Hodgkin lymphoma
|
|
|
methotrexate - mechanism
|
folate antagonist --> structural analog of folic acid that INHIBITS dihydrofolate reductase = depletes intracellular FH4
|
|
|
adverse effects of methotrexate
|
1. bone marrow depression
2. GI damage 3. pneumonitis 4. nephrotoxicity w/ high doses |
|
|
leucovorin
|
folinic acid
--> given w/ folate antagonists to rescue |
|
|
therapeutic uses of methotrexate (5)
|
1. leukemias
2. lymphomas 3. breast cancer 4. RA 5. psoriasis |
|
|
5-fluorouracil - mechanism
|
pyrimidine antimetabolite (uracil analogue) that interferes w/ dTMP synthesis --> inhibits DNA synthesis
|
|
|
therapeutic use of 5-FU
|
topically for basal cell carcinoma and keratosis
alternatively for breast, ovarian and head/neck cancer |
|
|
unwanted effects of 5FU (4)
|
1. myelotoxicity
2. GI upset 3. cerebellar disturbances 4. cardiotoxicity |
|
|
capecitabine
|
metabolized to 5FU
--> tx. of metastatic breast cancer |
|
|
what are the pyrimidine analogs? (4)
|
5-FU
capecitabine cytarabine gemcitabine |
|
|
cytarabine - mechanism
|
cytosine arabinoside --> analog of 2-deoxycytidine
INHIBITS DNA polymerase |
|
|
unwanted effects of cytarabine (4)
|
1. NVD
2. myelosuppression - severe 3. hepatic dysfunction 4. seizures w/ intrathecal use |
|
|
clinical use of cytarabine
|
AML
|
|
|
gemcitabine
|
newer analogue of cytarabine w/ fewer side effects
- usually given in combo w/ cisplatin |
|
|
unwanted effects of gemcitabine (2)
|
1. mild myelotoxicity
2. flu-like syndrome |
|
|
6-mercaptopurine
|
thiol analogue of hypoxanthine
--> purine antimetabolite bioactivated by HGPRT |
|
|
clinical uses of 6-MP (2)
|
1. ALL
2. immunosuppression |
|
|
adverse effects of 6MP (5)
|
1. NVD
2. mild myelotoxicity 3. thrombocytopenia 4. hepatotoxicity - jaundice, necrosis 5. increased levels w/ allopurinol |
|
|
what are the purine antimetabolites?
|
1. 6-mercaptopurine
2. 6-thioguanine 3. fludarabine 4. cladiribine 5. pentostatin |
|
|
pentostatin
|
inhibits adenine deaminase
hypoxanthine analogue |
|
|
doxorubicin - mechanism (2)
|
1. intercalates w/ DNA by stabilizing topoisomerase II (DNA gyrase)
2. produces free radicals |
|
|
anthracycline antibiotics (6)
|
doxorubicin
daunorubicin idarubicin epirubicin aclarubicin mitoxantrone |
|
|
adverse effects of doxorubicin (5)
|
1. cardiotoxicity -> heart failure
2. alopecia 3. transient BMS 4. stomatitis 5. GI disturbances |
|
|
dexrazoxane
|
iron chelating agent preventing the formation of free radicals to alleviate cardiotoxicity of doxorubicin
|
|
|
therapeutic uses of doxorubicin
|
Hodgkin
breast cancer endometrial cancer ovarian cancer lung cancer |
|
|
daunorubicin
|
cytotoxic antibiotic --> used to treat AML
|
|
|
anthracycline antibiotics show synergism w/ (3)
|
1. cyclophosphamide
2. cisplatin 3. nitrosureas |
|
|
dactinomycin - mechanism
|
cytotoxic antibiotic
--> intercalates into DNA minor groove bw adj C-G pairs = prevents TXN --> inhibits DNA gyrase |
|
|
clinical uses of dactinomycin
|
pediatric tumors (Wilm's tumor)
soft tissue sarcoma |
|
|
bleomycin -mechanism
|
metal chelating glycopeptide antibiotic
--> complexes w. Fe and O2 to cause strand scission |
|
|
clinical use of bleomycin
|
germ line cancers
w/ vinblastine and cisplatinum |
|
|
adverse effects of bleomycin (7)
|
1 pulmonary fibrosis
2 pneumonitis 3 allergic reactions 4 mucocutaneous reactions 5 hyperpyrexia 6 alopecia 7 skin hypertrophy |
|
|
mitomycin - mechanism
|
alkylating agent that cross links DNA and degrades DNA through generation of ROS
|
|
|
hydroxycarbamide
|
urea analogue that inhibits ribonucleotide reductase
- used mainly to Tx. leukemias |
|
|
plicamycin
|
disrupts DNA --> specific for osteoclasts
--> lowers plasma Ca2+ in pts w/ bone tumors |
|
|
adverse effect of plicamycin
|
hemorrhage
|
|
|
mitoxantrone
|
breaks DNA strands --> inhibiting DNA and RNA synthesis (similar to anthracyclin antibiotics)
|
|
|
adverse effect of mitoxantrone
|
arrhythmias
|
|
|
vinca alkaloids (4)
|
vincristine
vinblastine vindesine vinorelbine |
|
|
mechanism of action of Vinca Alkaloids (3)
|
1. bind tubulin and inhibit MT polymerization
2. inhibit leukocyte phagocytosis and chemotaxis 3. inhibit neuronal transport in axons |
|
|
vincristine - adverse effects
|
mild BMS
neurotoxic --> paresthesias, mm weakness |
|
|
vinblastine - adverse effects
|
less neurotoxic
more BMS - leukopenia |
|
|
taxanes - mechanism
|
act on microtubules to stabilize them in polymerized state --> prevent depolarization
|
|
|
taxanes - examples
|
1. paclitaxel
2. doclitaxel |
|
|
adverse effects of taxanes (4)
|
1. BMS
2. cumulative neurotoxicity 3. resistant fluid retention - doclitaxel 4. hypersensitivity |
|
|
etoposide/teniposide - mechanism
|
inhibit mitochondrial function and nucleoside transport in cells
|
|
|
adverse effects of etoposide (4)
|
1. NV
2. myelosuppression 3. hair loss 4. hypotension |
|
|
campothecins
- mechanism (1) - examples (2) - adverse effects (3), (4) |
1. inhibit topoisomerase I
2. irinotecan, topotecan 3. diarrhea 4. reversible bone marrow suppression |
|
|
glucocorticoids are useful in Tx. of which cancers?
|
leukemias and lymphomas
|
|
|
trilostane
|
glucocorticoid that inhibits P4 synthesis
|
|
|
estrogens such as (1) and (2) are used to Tx. (3) and (4)
|
1. diethylstilbestrol
2. ethinyl estradiol 3. palliative tx. of androgen-dep prostatic tumors 4. recruit mammary cells to proliferating pool, to facilitate killing by other drugs |
|
|
tamoxifen
|
competes w/ endogenous estrogens at the estrogen receptor
|
|
|
tamoxifen is used in treatment of ...
|
hormone dependent breast cancer
|
|
|
adverse effects of tamoxifen (5)
|
1. menopausal symptoms - hot flashes
2. NVD 3. skin rash 4. vaginal bleeding 5. increases pain in metastatic bone tumors |
|
|
aromatase inhibitors (3)
|
1. anastrozole
2. letrozole 3. exemestane |
|
|
aminoglutethimide
|
blocks generation of all steroids --> largely replaced by aromatase inhibitors
|
|
|
rituximab - mechanism
|
monoclonal antibody
--> binds to CD20 on B cells and activates their lysis by complement |
|
|
trastuzumab aka (1)
- binds to (2) and induces (3) - often given with (4) to treat (5) |
1. herceptin
2. HER2 3. cell cycle inhibitors p21 and p27 4. taxane 5. aggressive breast cancer |
|
|
imatinib mesylate
- inhibits (1) - treatment of (2) |
1. PDGF
2. chronic myeloid leukemia resistant to other therapy |
|
|
what are the anti-androgens?
|
1. flutamide
2. cyproterone |
|
|
what are the progestins ? (1), (2)
what are they used to Tx ? (3) and (4) |
1. megestrol
2. medroxyprogesterone 3. endometrial cancer 4. renal tumors |
|
|
GnRH-agonists (3)
- action (4) - used in (5) |
1. leuprolide
2. goserelin 3. buserelin 4. inhibit LH/FSH release = reduction in androgen synthesis 5.prostate cancer |
|
|
octreotide
|
somatostatin analogue
--> reduces hormone secreting VIPomas, glucagonomas, carcinoids and gastrinomas |
|
|
L-asparaginase aka (1)
- mechanism (2) - clinical use (3) |
1. crisantaspase
2. catalyze deamination of asparagine to aspartic acid and ammonia --> tumors do not form enough asparagine 3. acute lymphocytic leukemia |
|
|
adverse reactions of L-asparaginase (6)
|
1. hypersensitivity
2. decrease in clotting factors 3. liver dysfunction 4. pancreatitis 5. seizures/coma 6. NV |
