Pharm Topic 11: Cancer Chemo

Front 1

Growth Fraction

Back 1

Percentage of tumor cells which are dividing.

Front 2

Reasons why multiple drugs are used in chemo

Back 2

1) Resistance rapidly develops to a single drug.
2) Tumor cells are heterogenous and not all cells are equally sensitive to the same drug.
3) Each drug independently gives log kill

Front 3

What is the guide for drug selection

Back 3

1) Use drugs which are effective alone
2) " " " have different mechs of action (therefore cells cant develop resistance to both).
3) " " whose toxicity doesnt overlap
4) " " that are compatable with the patients age and health status.

Front 4

Adjuvant therapy

Back 4

Treatment to block the recurrence of cancer following removal of a tumor via surgery or radiation

Front 5

Name the DNA damaging drugs

Back 5

Cyclophosphamide
Mensa (used with DNA damaging drugs)
Cisplatin
Bleomycin
Doxorubicin

Front 6

Cyclophosphamide (Mech, toxicity, cell cycle,)

Back 6

Mech - Activated by p450. Bind and cross link DNA preventing DNA replication and RNA synth.
Toxicity - BM (also causes hemorrhagic cystitis)
Cell cycle - N/A

Front 7

Mensa (Mech, toxicity, cell cycle)

Back 7

Mech - Used in conjunction with Cyclophosphamide to prevent hemoorhagic cystitis by inactivating acolein; the metabolite of cyclo which causes the damage.
Toxicity - N/A
CC - N/A

Front 8

Cisplatin (Mech, toxicity, cell cycle)

Back 8

Mech - Bind and cross link DNA preventing DNA replication and RNA synth.
Tox - Renal
CC - N/A

Front 9

Bleomycin (Mech, toxicity, cell cycle)

Back 9

Mech - Metabolically activated via microsomal reduction, metabolite intercalates between DNA strands and cleaves via free radicals.
TOX - Pulmonary
CC - M and G2

Front 10

Doxorubicin (Mech, toxicity, cell cycle)

Back 10

Mech - Intercalates between DNA, freezes topo 2 resulting in DNA breaks
TOX - Cardiac and BM

Front 11

Name the Antimetabolite drugs

Back 11

1) Methotrexate
2) Leucovorin
3) Floururacil
4) Mercaptopurine

Front 12

Methotrexate (Mech, toxicity, cell cycle)

Back 12

Mech - Folic acid analog which works via competitive inhibition. Leads to pyrimidine and purine shortage. This impaired DNA synth can cause death. Also effects protein synth via actions on glycine and methionine.
TOX - BM
CC - S phase

Front 13

Leucovorin (Mech, toxicity, cell cycle)

Back 13

Mech - Given if high doses of methotrexate must be given. Can be used for purine and pyrimidine synth rescuing healthy cells. Many tumors cant take up Leucovorin.
TOX - NA
CC - NA

Front 14

Florouracil (Mech, toxicity, cell cycle)

Back 14

Mech - Uracil derivative. Tumor cells rapidly use up uracil for RNA and DNA synth. When they incorporate florouracil, 28S ribosome becomes truncated. If incorporated into DNA, it causes strand breaks. Also prevents conversion of dUMP to dTMP resulting in neucleotide imbalance and DNA cleaving. (Only used in solid tumors, not effective in leukemias)
TOX - BM
CC - Non specific

Front 15

Mercaptopurine (Mech, toxicity, cell cycle)

Back 15

Mech - Purine analog which causes feedback inhibition of first step in purine synth, decreases purine levels. When incorporated, cause DNA strand breaks and inhibition of RNA synth.
Tox - BM
CC - S phase

Front 16

Name the mitosis inhibitors

Back 16

Paclitaxel

Front 17

Paclitaxel (Mech, toxicity, cell cycle)

Back 17

Mech - Bind to tubulin and screw up microtubule formation and mitotic spindle formation.
Tox - Neutropenia (of BM)
CC - M phase

Front 18

Tamoxifen (Breast, Bone, Endometrium, Mech, TOX)

Back 18

Breast: -
Bone: +
Endo: +
Mech: Binds to estrogen receptor
TOX: Endo cancer in post M women and increased blood clots so only used in pre. Fetal tox.

Front 19

Raloxifene

Back 19

Breast: -
Bone: +
Endo: -
Mech: Binds to Estrogen receptor.
TOX: Blood clots in post M women and fetal tox

Front 20

Letrozole

Back 20

Breast: -
Bone: -
Endo: -
Mech: Inhibit Aromatase which converts androgens to estrogens in adrenal tissues. Only for Post M women b/c not strong enough to inhibit ovary secretion. Also used as adjuvant therapy for post M women.
Tox: Fetal harm

Front 21

Fluvestrant

Back 21

Breast: -
Bone: -
Endo: -
Mech: Estrogen receptor antagonist which binds receptor and causes down regulation. Used for post M women.
TOX: fetal tox

Front 22

Herceptin (Mech, toxicity, cell cycle)

Back 22

Mech - Humanized Ig which targets HER2 gene product which is a receptor found on 25-30% of breast cancer tumor cells.
TOX - Cardiac failure via congestive with decreased left vent ejac. Also can get allergic Rx
CC - NA

Front 23

Estrogen blocking Breast Cancer Drugs

Back 23

1) Tamoxifen
2) Raloxifene
3) Letrozole
4) Fulvestrant

Front 24

DES

Back 24

Prostate cancer drug.
Mech - Causes feedback inhibition of LH and FSH leading to decreased testosterone production.

Front 25

Aminoglutethimide

Back 25

Prostate cancer drug.
Mech - Inhibits conversion of cholesterol to pregnenolone decreasing androgen (testosterone) production.

Front 26

Leuprolide

Back 26

Prostate cancer drug.
GnRH superagonist which causes desensitization of pituitary gland to GnRH reducing LH and FSH production (and therefore testosterone).

Front 27

Flutamide

Back 27

Prostate cancer drug.
Mech - Blocks binding of androgens to their receptors on the prostate. This does have the undesirable effect of decreasing androgen mediated feedback of FSH and LH and therefore is coupled with leuprolide.

Front 28

What supplements must you give men taking prostate hormone therapy drugs?

Back 28

Cortisol, aldosterone, and corticosterone.

Front 29

Hormone therapy prostate cancer drugs

Back 29

1) DES
2) Aminoglutethimide
3) Leuprolide
4) Flutamide

Front 30

Prednisone

Back 30

Synthetic glucocorticoid. In lymphoid tissues, induce cell death via inducing transcription of capsases. Dont suppress BM. Good for lymphomas and lympholytic anemias.
Tox - Hyperadrenocortisism and all the side effects that would entail.

Front 31

Gleevec

Back 31

Used to treat CML.
Binds to the ATP binding site of a mutant tyrosine kinases (PDGF, bcr-Able, and kit) preventing its catalytic activity. Is metabolized by p450.
Tox - Mild nasuea and such, not given to pregnant women.

Front 32

Tykerb

Back 32

For breast cancer. Inhibits EGFR receptor by binding to ATP binding site and preventing catalytic activity.
TOx - Nasea, decreased left ventricle ejac., hepatotoxicity, and is a teratogen.

Front 33

What drug combination is used to treat cervical carcenoma?

Back 33

Cisplatin + bleomycin + methotrexate

Front 34

Which ones are high risk and which ones are low for their carcinogenic properties: Methotrexate, Florouracil, and cyclophosphamide

Back 34

Cyclo = High risk
Metho and Floro = Low risk