Pharmacology - Cancer

Front 1

Cell Cycle Specific Drugs:
-name them (5)

Back 1

1. antimetabolites (MTX, 5-FU, 6-MP)
2. etoposide
3. bleomycin
4. vinca alkaloids
5. paclitaxel

Front 2

Cell Cycle Nonspecific Drugs:
-name them (2)

Back 2

1. alkylating agents
2. antibiotics (dactinomycin, doxorubicin, bleomycin)

Front 3

Site of action - name cancer drug:
1. nucleotide synthesis
2. DNA
3. mRNA
4. protein

Back 3

1a. MTX + 5-FU - decrease thymidine synth
1b. 6-MP - decrease purine synth
1c. Cytarabine
2a. Alkylating agents + cisplatin - DNA cross-linkage
2b. Dactinomycin + doxorubicin - DNA intercalation
2c. Bleomycin - strand breakage + DNA intercalation
2d. Etoposide - strand breakage
3. Steroids
4a. Tamoxifen
4b. Vinca alkaloids - inhibit MT formation
4c. Paclitaxel - inhib MT disassembly

Front 4

Which drugs block...
1. S phase
2. G2 phase
3. M phase

Back 4

1. antimetabolites, etoposide
2. bleomycin, etoposide
3. vinca alkaloids, taxols

Front 5

Methotrexate (MTX)
-mech

Back 5

-S-phase specific antimetabolite
-folic acid analog that inhibits DIHYDROFOLATE REDUCTASE (decreases dTMP -> decr DNA and prot synth)

Front 6

MTX
-clin use

Back 6

-leukemias, lymphomas
-choriocarcinoma, sarcomas
-abortion, ectopic pregnancy
-rheumatoid arthritis, psoriasis

Front 7

MTX
-toxicity?
-reversible with?

Back 7

-MYELOSUPPRESSION reversible with LEUCOVORIN (folinic acid) rescue
-Macrovesicular fatty change in liver

Front 8

5-Fluorouracil (5-FU)
-mechanism

Back 8

-S-phase specific antimetabolite
-pyrimidine analog bioactivated to 5F-dUMP (covalently complexes folic acid)- inhibits THYMIDYLATE SYNTHASE) -results in decreased dTMP and same effects as MTX

Front 9

5-FU
-clin use

Back 9

-colon CA, other solid tumors
-BCC (topical)

*SYNERGY with MTX

Front 10

5-FU
-toxicity? rescue?

Back 10

-Myelosuppresion *NOT reversible with leucovorin
-PHOTOSENSITIVITY
-can "rescue" with THYMIDINE

Front 11

6-mercaptopurine (6-mp)
-mech
-clin use

Back 11

-blocks de novo purine synthesis
-activated by HGPRTase

-for leukemias, lymphomas (not CLL or Hodgkins')

Front 12

6-MP
-toxicity
-metabolized by? what drug increases 6-MP toxicity

Back 12

-bone marrow, GI, liver
*Metabolized by XANTHINE OXIDASE (thus increased toxicity with ALLOPURINOL)

Front 13

Cytarabine (ara-C)
-mech
-clin use
-tox

Back 13

-Inhibits DNA polymerase
-AML
-tox: leukopenia, thrombocytopenia, megaloblastic anemia

Front 14

Cyclophosphamide, ifosfamide
-mechanism
-need bioactivation?

Back 14

Alkylating agents
-covalently x-link (interstrand) DNA at guanine N-7
*Require bioactivation by liver

Front 15

Cyclophophamide, ifosfamide
-clin use

Back 15

Non-hodkin's lymphoma
Breast and Ovarian CA
Immunosuppressants

Front 16

Cyclophosphamide, ifosfamide
-toxicity? prevention?

Back 16

-Myelosuppression
-HEMORRHAGIC SYSTITIS (partially prevented tih MESNA)

Front 17

Mesna - mechanism
-neutralize which metabolits?
-what moieties
-increase urinary excretion of?

Back 17

In vivo, cyclophos/ifosfamide may be converted to urotoxic metabolites such as acrolein. Mesna assists to neutralise these metabolites by binding through its sulfhydryl-moieties, and also increases urinary excretion of cysteine.

Front 18

Nitrosureas
-name them (4)
"CLSS"

Back 18

Carmustine
Lomustine
Semustine
Streptozocin

Front 19

Nitrosureas
-mech
-req bioactivation?

Back 19

Alkylate DNA
Require bioactivatio
Cross BBB - CNS

Front 20

Nitrosureas
-clin use
-toxicity

Back 20

-for brain tumors (including glioblastoma multiforme)
-tox: CNS toxicity (dizzy, ataxia)

Front 21

What drugs used for glioblastoma multiforme?

Back 21

Nitrosureas?
-carmustine
-lomustine
-semusteim
-streptozocin

Front 22

Cisplatin, carboplatin
-mech
-clin use
-toxicity

Back 22

-act like alkylating agents
-for Testicular, Bladder, Ovary, and Lung CAs
-tox: NEPHROTOXIC, ACOUSTIC NERVE DAMAGE

Front 23

Busulfan
-mech
-clin use
-toxicity

Back 23

-alkylates DNA
*for CML

tox: PULMONARY FIBROSIS, HYPERPIGMENTATION

Front 24

Doxorubicin (Adriamycin), daunorubicin
-mechanism

Back 24

-generates free radicals
-non covalently intercalate in DNA (create DNA strand breaks, decreasing replication)

Front 25

Doxorubicin (Adriamycin), daunorubicin
-clin use

Back 25

*part of ABVD combination regimen for Hodgkin's and for myelomas, sarcomas, and solid tumors (breast, ovary, lung)

Front 26

Doxorubicin (adriamycin), daunorubisin
-toxicity

Back 26

CARDIOTOXICITY
MYELOSUPPRESSION
*MARKED ALOPECIA
Toxic extravasation

Front 27

Dactinomycin (actinomycin D)
-mech
-clin use
-toxicity
Hint: "children ACT out"

Back 27

-intercalates in DNA
-clin use: WILMS's tumor, EWING's sarcoma, RHABDOmyosarcoma
-tox: myelosuppression

Front 28

Bleomycin
-mech
-clin use
-tox

Back 28

-induces formation of free radicals - causes breaks in DNA strands
-for Testicular CA, lymphomas (part of ABVD regimen for Hodgkins')
-tox: PULMONARY FIBROSIS, skin changes *minimal myelosuppression*

Front 29

Etoposide (VP-16)
-mech

Back 29

-G2-phase specific agent that inhibits TOPOISOMERASE II and increases DNA degradation

Front 30

Etoposide (VP-16)
-clinical use
-tox

Back 30

Small cell CA of LUNG and PROSTATE; TESTICULAR CA

tox: myelosuppression, GI irritaiton, alopecia

Front 31

Prednisone
-mech

Back 31

-may trigger apoptosis
-may even work on nondividing cells

Front 32

Prednisone
-clin use

Back 32

-most commonly used glucocorticoid in CA chemotherapy
-CLL
-Hodgkin's lympohomas (part of MOPP regiment)
-also immunosuppressant in autoimmune dz

Front 33

Prednisone
-tox

Back 33

Cushing-like sxs
immunosuppression
CATARACTS
acne
osteoporosis
HTN
peptic ulcers
hyperglycemia
psychosis

Front 34

Tamoxifen, raloxifene
-mech

Back 34

-receptor antagonist in breat
-agonist in bone
-blocks binding of E to E-receptor+ cells

Front 35

Tamoxifen, raloxifene
-clin use

Back 35

-breast cancer
-prevent osteoporosis

Front 36

Tamoxifen, raloxifene
-Toxicity (tamox vs. ralox)

Back 36

Tamoxifene: may increase risk of endometrial CA via partial agonist effects, hot flashes

Raloxifene - does not cause endometrial CA b/c it's an endometrial ANTAGoNIST

Front 37

Trastuzumab (herceptin)
-mechanism

Back 37

-monoclonal ab vs HER-2 (erb-B2)
-helps kill breast CA cells that overexpress HER-2, possibly through antibody-dependent cytotoxicity

Front 38

Trastuzumab - other name?

Back 38

Herceptin

Front 39

Trastuzumab
-clin use
-tox

Back 39

-for METASTATIC breast CA
-may cause cardiotoxicity

Front 40

Imatinib (gleevec)
-mech
-clin use
-toxicity

Back 40

Philadelphia chromosome brc-able tyrosine kinase inhibitor
-for CML and GI stromal tumors

tox: fluid retention

Front 41

Vincristine, Vinblastine
-mechanism

Back 41

-M-phase sepcific alkaloids that bind to tubulin and block polymerization of MTs so that mitotic spindle cannot form

Front 42

Vincristine, Vinblastine
-clin use

Back 42

part of MOPP (Oncovin [vincristine]) regimen for lymphoma, Wilm's tumor, choriocarcinoma

Front 43

Vincristine vs. Vinblastine
-toxicity

Back 43

Vincristine: NEUROTOXICITY (areflexia, peripheral neuritis) + PARALYTIC ILEUS

VinBLASTine BLASTS Bone marrow (suppression)

Front 44

Paclitaxel, other taxols
-mech

Back 44

M-phase specific agents that bin to tubulin and hyperstabilize polymerized MTs so that mitotic spindle cannot break down (anaphase cannot occur)

Front 45

Paclitaxel, other taxols,
-clin use
-tox

Back 45

-for OVARIAN and BREAST CAs

-tox: Myelosuppression and Hypersenstivity