Ph28-Antineoplastics I

Front 1

What are the major alkylating agents?

Back 1

Nitrogen mustards (cyclophosphamides, melphalan), Alkyl sulfonates (busulfan), & Nitrosoureas (BCNU, CCNU, MeCCNU)

Front 2

MOA of alkylating agents?

Back 2

As strong electrophile adds alkyl group to nucleophiles via SN2 rxn. DNA guanine most suspeptible-> mispairing or cross linking-> pt mutation. (G+C)-> (T+A). Most effective on prolif cells during s phase (not cell cycle specific)

Front 3

Charac of cyclophosphamide?

Back 3

Must be activated via p450 in liver

Front 4

Clinical uses of alkylating agent?

Back 4

Hodgkins, lymphomas, multiple myeloma, breast, ovarian,melanoma, peripheral stem cell mobilization

Front 5

Toxicities of alkylating agents?

Back 5

Myelosuppression, hemorrhagic cystitis, sterility, secondary leukemia

Front 6

What are the antibiotics that are used as chemo?

Back 6

Anthracyclines (Daunorubicin, doxorubicin, Idarubicin, mitoxantrone), bleomycin, dactinomycin, mitomycin c

Front 7

MOA of anthracyclines?

Back 7

Intercalate into DNA & prevent replication, react w/ p450 generate free radicals (requires Fe), inducing DNA breaks (topoismerase II inhibitors)

Front 8

Uses of anthrayclins?

Back 8

Acute leukemia, lymphomas, breast, & sarcomas

Front 9

Toxicities of antracyclines?

Back 9

Cardiotoxicity, myelosuppression, vesicants

Front 10

MOA of bleomycin?

Back 10

Binds Fe & reacts w/ molec oxy to cause free radical-> DNA strand breaks

Front 11

Clinical uses of bleomycin?

Back 11

Testicular cancer, lymphomas, Hodgkin's

Front 12

Toxicitis of bleomycin?

Back 12

pulmonary fibrosis

Front 13

MOA of dactinomycin?

Back 13

Intercalated b/w guanosine-cytosine pairs in DNA-> blocks transcription

Front 14

Clinical uses of dactomycin?

Back 14

Wilm's tumor, rhabdomyosarcoma, Kaposi's, gestational choriocarcinoma, Hodgkin's

Front 15

Toxicities of dactomycin?

Back 15

Myelosuppression

Front 16

MOA of mitomycin C?

Back 16

Alkylates DNA by cross-linking @ N6 adenine & N7 guanine

Front 17

Clinical uses of mitomycin C?

Back 17

GI, Head/neck, anal

Front 18

Toxicities of mitomycin C?

Back 18

Late myelosuppression

Front 19

Classes of antimetabolites?

Back 19

Folic acid analogs, pyrimidine analogs, & purine analogs

Front 20

MOA of antimetabolites

Back 20

Substitute an enzyme substrates or cofactors & inhibit purine or pyrimidine biosynthesis. Are S phase specific

Front 21

Class of methotrexate

Back 21

Folic acid analog

Front 22

MOA of methotrexate?

Back 22

Inhibits de novo thymidylate & purine synthesis. Incorporate dUTP into DNA resulting in inhibition of DNA synthesis & fcn

Front 23

Name pyrimidine analogs

Back 23

5-fluorouracil, Cytosine arabinoside, & 2,2-difluorodeoxycytidine (gemcitibine)

Front 24

MOA of pyrimidine analogs?

Back 24

Inhibit conversion of orotic acid to uridine (UMP)-> impair nucleic acid synthesis, can incorporate into DNA/RNA-> pt mutations, & can inhibit thymidine synthesis

Front 25

Name purine analogs

Back 25

6-thioguanine, 6-mecaptopurine, fludarabine, pentostatin, 2-CdA

Front 26

MOA of 6-thioguanine & 6-mecaptopurine

Back 26

Thioinosine inhibits adenine & guanine synthesis

Front 27

MOA of Fludarabine

Back 27

Inhibit DNA polymerase, DNA primase, & ribonucleotide reductase. IS incorporated into DNA & RNA

Front 28

MOA of 2' deoxycoformycin

Back 28

inhibits adenosine deaminase-> accumulation of intracellular adenosine & deoxyadenosine-> blocks DNA synthesis by inhibiting ribonucleotide reductase

Front 29

MOA of chlorodeoxyadenosine

Back 29

It’s a adenosine deaminase resistant purine analog that induces DNA strand breaks. Also induces NAD & ATP depletion & apop

Front 30

Clinical use of methotrxate

Back 30

acute lymphoblastic leukemia, osteosarcoma, lymphoma, carcinoma of the breast, ovary, bladder, head and neck, psoriasis, and rheumatoid arthritis

Front 31

Clinical use of 5-FU

Back 31

breast and colon cancer, esophageal cancer, squamous cell carcinoma of the head and neck

Front 32

Clinical use of ara C

Back 32

myeloid leukemia and lymphoma

Front 33

Clinical use of gemcitibine

Back 33

pancreatic cancer, non-small cell lung cancer

Front 34

Clinical use of 6-thioguanine

Back 34

acute lymphoblastic leukemia

Front 35

Clinical use of fludaribine

Back 35

chronic lymphocytic leukemia, low grade lymphoma

Front 36

Clinical use of 2' deoxycoformycin

Back 36

hairy cell leukemia, T- and B-cell lymphomas

Front 37

Clincal use of 2'chlorodeoxyadenosine

Back 37

cell leukemia, chronic lymphocytic leukemia, low grade lymphoma

Front 38

Toxicity of 5-FU

Back 38

myelosuppression, hemorrhagic cystitis

Front 39

Toxicity of ara C

Back 39

mucositis, diarrhea

Front 40

Toxicity of gemcitibine

Back 40

myelosuppression, flu-like syndrome

Front 41

Toxicity of 6-thioguanine

Back 41

myelosuppression

Front 42

Toxicity of fludaribine

Back 42

myelosuppression, CD4 T cell depletion, peripheral neuropathy

Front 43

Toxicity of 2' deoxycoformycin

Back 43

myelosuppression

Front 44

Toxicity of 2'chlorodeoxyadenosine

Back 44

myelosuppression, especially thrombocytopenia

Front 45

Biochemical modulation of 5FU by leucovorin

Back 45

5FU is converted to FdUMP which inhibits thymidylate synthase & 5, 10 methylene tetrahydrofolate, which inhibits de novo synthesis of pyrimidines & DNA synthesis. Leucovorin stabilizes FdUMP-thymidylate synthase -5, 10-methylene tetrahydrofolate ternary complex increasing 5FU potency