Oncology Rx

Question 1

Methotrexate (MTX)

Answer 1

1) CA: leukemia, lymphoma, choriocarcinoma, sarcoma; non-CA: abortion, ectopic preg, rheumatoid arthritis, psoriasis 2) folate analog: inhibits DHFR –> decr dTMP –> decr DNA + protein syn 3) myelosuppression (reverse w/ leucovorin); macrovesicular fatty liver change; mucositis; teratogenic 4) S-phase specific

Question 2

5-fluorouracil (5-FU)

Answer 2

1) colon CA, basal cell carcinoma (topical) 2) pyrimidine analog bioactivated to 5F-dUMP (covalently complexes folate) –> complex inhibits thymidylate synthase –> decr dTMP –> decr DNA + protein syn 3) myelosuppression (not reversible w/ leucovorin); OD rescue w/ thymidine; photosensitivity 4) S-phase specific

Question 3

Cytarabine (arabinofuranosyl cytidine)

Answer 3

1) leukemia, lymphoma 2) pyrimidine analog –> inhibit DNA polymerase 3) leukopenia, thrombocytopenia, megaloblastic anemia 4) S-phase specific

Question 4

Azathioprine

Answer 4

1) leukemias 2) purine (thiol) analog –> decr de novo purine syn 3) BM, GI, liver; metabolized by xanthine oxidase so incr toxicity w/ allopurinol 4) S-phase specific; activated by HGPRT

Question 5

6-mercaptopurine (6-MP)

Answer 5

1) leukemias 2) purine (thiol) analog –> decr de novo purine syn 3) BM, GI, liver; metabolized by xanthine oxidase so incr toxicity w/ allopurinol 4) S-phase specific; activated by HGPRT

Question 6

6-thioguanine (6-TG)

Answer 6

1) leukemias 2) purine (thiol) analog –> decr de novo purine syn 3) BM, GI, liver; metabolized by xanthine oxidase so incr toxicity w/ allopurinol 4) S-phase specific; activated by HGPRT

Question 7

Dactinomycin (actinomycin D)

Answer 7

1) Wilm’s tumor, Ewin’s sarcoma, rhabdomyosarcoma; peds tumors 2) intercalates in DNA 3) myelosuppression 4) N/A

Question 8

Doxorubicin (Adriamycin)

Answer 8

1) solid tumors, leukemias, lymphomas 2) makes ROS; non-covalently intercalate in DNA –> breaks DNA –> decr replication 3) cardiotoxicity* (dilated cardiomyopathy; use dexrazoxane, Fe chelator, to prevent), myelosuppression, alopecia; toxic to tissues following extravasation 4) N/A

Question 9

Daunorubicin

Answer 9

1) solid tumors, leukemias, lymphomas 2) makes ROS; non-covalently intercalate in DNA –> breaks DNA –> decr replication 3) cardiotoxicity* (dilated cardiomyopathy; use dexrazoxane, Fe chelator, to prevent), myelosuppression, alopecia; toxic to tissues following extravasation 4) N/A

Question 10

Bleomycin

Answer 10

1) testicular CA, Hodgkin’s lymphoma 2) ROS formation –> causes breaks in DNA strands 3) pulm fibrosis*, skin changes; minimal myelosuppression 4) N/A

Question 11

Cyclophosphamide

Answer 11

1) solid tumors, leukemia, lymphoma, some brain CAs 2) alkylating agent: covalently X-link DNA at guanine N-7 3) myelosuppression; hemorrhagic cystitis (partly prevent w/ mesna, thiol grp of mesna binds toxic metabolite) 4) need liver bioactivation

Question 12

Ifosfamide

Answer 12

1) solid tumors, leukemia, lymphoma, some brain CAs 2) alkylating agent: covalently X-link DNA at guanine N-7 3) myelosuppression; hemorrhagic cystitis (partly prevent w/ mesna, thiol grp of mesna binds toxic metabolite) 4) need liver bioactivation

Question 13

Carmustine

Answer 13

1) brain tumors (incl glioblastoma multiforme) 2) alkylating agent: nitrosourea 3) CNS toxicity: dizziness, ataxia 4) needs bioactivation; X’s BBB –> CNS

Question 14

Lomustine

Answer 14

1) brain tumors (incl glioblastoma multiforme) 2) alkylating agent: nitrosourea 3) CNS toxicity: dizziness, ataxia 4) needs bioactivation; X’s BBB –> CNS

Question 15

Semustine

Answer 15

1) brain tumors (incl glioblastoma multiforme) 2) alkylating agent: nitrosourea 3) CNS toxicity: dizziness, ataxia 4) needs bioactivation; X’s BBB –> CNS

Question 16

Streptozocin

Answer 16

1) brain tumors (incl glioblastoma multiforme) 2) alkylating agent: nitrosourea 3) CNS toxicity: dizziness, ataxia 4) needs bioactivation; X’s BBB –> CNS

Question 17

Busulfan

Answer 17

1) CML; also to ablate BM before BMT 2) alkylating agent 3) pulm fibrosis*; hyperpigmentation 4) N/A

Question 18

Vincristine

Answer 18

1) solid tumors, leukemias, lymphomas 2) microtubule inhibitor: alkaloid that binds to tubulin in M phase + blocks polymerization so mitotic spindle can’t form 3) neurotoxicity: areflexia, periph neuritis; paralytic ileus 4) N/A

Question 19

Vinblastine

Answer 19

1) solid tumors, leukemias, lymphomas 2) microtubule inhibitor: alkaloid that binds to tubulin in M phase + blocks polymerization so mitotic spindle can’t form 3) BM suppression (VinBLASTine BLASTS Bone Marrow) 4) N/A

Question 20

Paclitaxel

Answer 20

1) ovarian + breast carcinomas 2) microtubule inhibitor: hyperstabilizes polymerized microtubules in M phase so mitotic spindle can’t break down (blocks anaphase) 3) myelosuppression, hypersensitivity 4) N/A

Question 21

Cisplatin

Answer 21

1) testicular, bladder, ovary, lung carcinomas 2) X-links DNA 3) nephrotoxicity (prevent w/ amifostine, ROS scavenger), acoustic nerve damage, chloride diuresis 4) N/A

Question 22

Carboplatin

Answer 22

1) testicular, bladder, ovary, lung carcinomas 2) X-links DNA 3) nephrotoxicity (prevent w/ amifostine, ROS scavenger), acoustic nerve damage, chloride diuresis 4) N/A

Question 23

Etoposide

Answer 23

1) solid tumors, leukemias, lymphomas 2) topo II inhibitor –> incr DNA degradation 3) myelosuppression, GI irritation, alopecia 4) N/A

Question 24

Teniposide

Answer 24

1) solid tumors, leukemias, lymphomas 2) topo II inhibitor –> incr DNA degradation 3) myelosuppression, GI irritation, alopecia 4) N/A

Question 25

Hydroxyurea

Answer 25

1) melanoma, CML, sickle cell dz (incr HbF) 2) inhibits ribonucleotide reductase --\> decr DNA syn (S-phase specific) 3) BM suppression, upset GI 4) N/A

Question 26

Prednisone

Answer 26

1) CA chemotx: CLL, non-Hodgkin's lymphomas; immunosuppressant (autoimmune dz) 2) glucocorticoid; may trigger apoptosis; may work on non-dividing cells 3) Cushing-like sx's; immunosuppression, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis 4) N/A

Question 27

Prednisolone

Answer 27

1) CA chemotx: CLL, non-Hodgkin's lymphomas; immunosuppressant (autoimmune dz) 2) glucocorticoid; may trigger apoptosis; may work on non-dividing cells 3) Cushing-like sx's; immunosuppression, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis 4) N/A

Question 28

Tamoxifen

Answer 28

1) breast CA tx + prophylaxis; prevent osteoporosis 2) SERM: R antagonist in breast + agonist in bone; block estrogen binding to ER+ cells 3) partial agonist in endometrium --\> incr endometrial CA risk; "hot falshes" 4) compare toxicity to raloxifene

Question 29

Raloxifene

Answer 29

1) breast CA tx + prophylaxis; prevent osteoporosis 2) SERM: R antagonist in breast + agonist in bone; block estrogen binding to ER+ cells 3) no incr in endometrial carcinoma b/c it's an endometrial antagonist 4) compare toxicity to tamoxifen

Question 30

Trastuzumab (Herceptin)

Answer 30

1) HER-2 (+) breast CA 2) monoclonal ab against HER-2 (c-erbB2), a tyrosine kinase --\> kill breast CA cells taht overexpress HER-2 (ab-dependent cytotoxicity) 3) cardiotoxicity 4) N/A

Question 31

Imatinib (Gleevec)

Answer 31

1) CML, GI stromal tumors 2) Ph chr bcr-abl tyroxine kinase inhibitor 3) fluid retention 4) N/A

Question 32

Rituximab

Answer 32

1) non-Hodgkin's lymphoma, rheumatoid arthritis (w/ MTX) 2) monoclonal ab against CD20 (found on most B-cell neoplasms) 3) N/A 4) N/A

Question 33

Vemurafenib

Answer 33

1) metastatic melanoma 2) small molec inhibitor of B-Raf kinases that have V600E mute 3) N/A 4) N/A

Question 34

Bevacizumab

Answer 34

1) solid tumors 2) monoclonal ab against VEGF --\> inhibits angiogenesis 3) N/A 4) N/A