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Pharmacology Unit 1 > Anticancer > Flashcards

Anticancer Flashcards

1
Q

Alkylating Agents

  1. MOA?
  2. Cell cycle specific?
  3. Toxicity?
  4. Resistance?
A
  1. produces strong electrophiles, covalent linkages by alkylating (N7 position of guanine)
  2. NON-SPECIFIC
  3. bone marrow, mucosal, N/V, reproductive systems, increased risk of leukemia
  4. production of glutathione (inactivates alkylating agents)
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2
Q

Four classes of alkylating agents?

A
  1. Nitrogen mustards
  2. Nitrosoureas
  3. Triazenes
  4. Platinum analogs
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3
Q

Bendamustine

  1. class of alkylating agent?
  2. Clinical uses?
  3. PEARLS?
A
  1. Nitrogen mustards
  2. Chronic lymphocytic leukemia (CLL), Non-hodgkin’s lymphoma (NHL)
  3. also inhibits mitotic checkpoints
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4
Q

Cyclophosphomide

  1. class of alkylating agent?
  2. clinical uses?
  3. PEARLS?
  4. special side effects?
A
  1. nitrogen mustards
  2. Hodgkin’s and non-Hodgkin’s lymphoma, breast, lung,
    and ovarian cancers
  3. very broad clinical spectrum, component of many combination regimens (CHOP, AC-T), pro-drugs & must be converted to active metabolites by cytochrome P450
  4. hemorrhagic cystitis
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5
Q

Ifosfamide

  1. class of alkylating agent?
  2. clinical uses?
  3. PEARLS?
  4. special side effects?
A
  1. nitrogen mustards
  2. sarcoma, testicular
  3. pro-drugs & must be converted to active metabolites by cytochrome P450
  4. encephalopathy, hemorrhagic cystitis rare
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6
Q

Carmustine and Lomustine

  1. class of alkylating agent?
  2. clinical uses?
  3. PEARLS?
  4. special side effects?
A
  1. nitrosoureas
  2. brain tumors
  3. highly lipophilic so crosses BBB
  4. CNS toxicity, profound myelosuppression, pulmonary fibrosis
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7
Q

Dacarbazine and Temozolomide

  1. class of alkylating agent?
  2. clinical uses?
  3. PEARLS?
  4. special side effects?
A
  1. Triazenes
  2. -Dacarbazine is a component of ABVD regimen used for treatment of Hodgkin’s lymphoma
    - Temozolomide is standard treatment of newly diagnosed glioblastoma (combined with radiation therapy)
  3. pro-drugs; monoalkylators
  4. nausea and vomiting, myelosuppression, flu-like symptoms (fever, fatigue etc.)
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8
Q

Cisplatin

  1. class of alkylating agent?
  2. clinical uses?
  3. PEARLS?
  4. special side effects?
A
  1. platinum analog
  2. testicular, ovarian, bladder, lung carcinomas, combination therapy
  3. wide-range of uses
  4. dose-limiting renal toxicity, ototoxicity, severe N/V, motor and sensory neuropathy
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9
Q

Carboplatin

  1. class of alkylating agent?
  2. clinical uses?
  3. special side effects?
A
  1. platinum analog
  2. ovarian cancer, lung
  3. myelosuppression
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10
Q

Oxaliplatin

  1. class of alkylating agent?
  2. clinical uses?
  3. special side effects?
A
  1. platinum analog
  2. gastric and colorectal cancers with 5FU comb
  3. neutropenia, COLD-INDUCED ACUTE PERIPHERAL NEUROPATHY
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11
Q

Antimetabolites

  1. MOA?
  2. Cell cycle specific?
A
  1. structural analogs of folic acid, purines or pyramidines which inhibit DNA synthesis
  2. cell cycle specific at S-phase
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12
Q

3 classes of antimetabolites?

A
  1. Folate analogs
  2. Pyrimidine analogs
  3. Purine analogs
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13
Q

Methotrexate

  1. class of antimetabolite?
  2. MOA?
  3. clinical uses?
  4. PEARLS?
  5. toxicity?
A
  1. folate analog
  2. inhibits DHFR
  3. childhood ALL, osteosarcoma, choriocarcinoma, Burkitt’s lymphoma, breast, ovarian, head/neck, bladder
  4. most widely used antimetabolite, CANNOT PENETRATE CNS
  5. bone marrow, renal, GI, hepatotoxicity, oogenesis/spermatogenesis
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14
Q

Pemetrexed

  1. class of antimetabolite?
  2. clinical uses?
A
  1. folate analog

2. colon cancer, mesothelioma, NSCLC, pancreatic cancer

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15
Q

5-Fluorouracil (5FU)

  1. class of antimetabolite?
  2. clinical uses?
  3. PEARLS?
  4. toxicity?
  5. oral prodrug version with less severe side effects?
A
  1. pyrimidine analog
  2. breast, colorectal, gastric, head/neck, cervical, pancreatic, topical for BCCA
  3. pro-drug, given IV due to rapid degradation
  4. anorexia, nausea, mucosal ulcerations, diarrhea, cardiac toxicity
  5. Capecitabine
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16
Q

Cytarabine

  1. class of antimetabolite?
  2. MOA?
  3. clinical uses?
  4. PEARLS?
  5. toxicity?
A
  1. pyrimidine analog
  2. premature DNA chain termination
  3. acute myeloid lymphoma (AML), ALL, blast phase CML
  4. most impt drug for AML, continuous IV administration
  5. severe myelosuppression, GI tract
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17
Q

Gemcitabine

  1. class of antimetabolite?
  2. MOA?
  3. clinical uses?
  4. PEARLS?
  5. toxicity?
A
  1. pyrimidine analog
  2. inhibits ribonucleotide reductase
  3. pancreatic cancer, NSCLC, ovarian, bladder, esophagus, head and neck
  4. more effective at solid tumors than cytarabine, active thru cell cycle (not S-phase specific)
  5. myelosuppression, flu-like symptoms
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18
Q

6-mercaptopurine (6MP)

  1. class of antimetabolite?
  2. MOA?
  3. clinical uses?
  4. PEARLS?
  5. toxicity?
A
  1. purine analog
  2. produces HGPRT –> TIMP which inhibits 1st step of purine base synthesis
  3. remission of ALL
  4. must lower dose if patients on allopurinol
  5. bone marrow, hepatotoxicity
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19
Q

Fludarabine

  1. class of antimetabolite?
  2. MOA?
  3. clinical uses?
  4. PEARLS?
  5. toxicity?
A
  1. purine analog
  2. interferes with ribonucleotide reductase and DNA polymerase
  3. leukemia, lymphoma
  4. ionized at physiological pH, trapped in blood
  5. lymphopenia, increased risk of opportunistic infections
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20
Q

DNA intercalating agents

  1. MOA?
  2. derived from?
  3. generates?
A
  1. block DNA and/or RNA synthesis
  2. soil microbe, Streptomyces
  3. free radicals
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21
Q

two classes of DNA intercalating agents?

A
  1. Anthracyclines

2. Bleomycin

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22
Q

Doxorubicin

  1. class of DNA intercalating agent?
  2. clinical uses?
A
  1. anthracycline
  2. broad spectrum; component of CHOP, ABVD, FAC

tx of sarcomas, breast cancer, lung cancer, lymphomas

23
Q

Daunoribicin and Idarubicin

  1. class of DNA intercalating agent?
  2. clinical uses?
A
  1. anthracycline

2. AML + Ara-C

24
Q

Epirubicin

  1. class of DNA intercalating agent?
  2. clinical uses?
A
  1. anthracycline

2. metastatic breast cancer (FEC combo)

25
Q

Mitoxantrone

  1. class of DNA intercalating agent?
  2. clinical uses?
  3. PEARL?
A
  1. anthracycline
  2. AML remission w/ cytarabine
  3. least cardiotoxic
26
Q

Toxicity seen in anthracyclines?

A

dose-limiting cardiotoxicity (cardiomyopathy)
neutropenia
stomatitis
alopecia

27
Q

Resistance seen in anthracyclines?

A

P-glycoprotein
increased glutathione peroxidase and/or catalase
increased DNA repair

28
Q

Bleomycin

  1. Class?
  2. MOA?
  3. Clinical uses?
  4. Toxicity?
A
  1. DNA intercalating agent
  2. binds to DNA to induce single or double stranded breaks, acts at G2 phase
  3. testicular carcinoma, hodgkin’s lymphoma, squamous cell carcinoma
  4. dose-related pulmonary toxicity, minimal myelosuppression, cutaneous changes
29
Q

2 classes of microtubule inhibitors?

when do they act?

A
  1. Vinca alkaloids
  2. Taxanes
  3. causes mitotic arrest at M phase
30
Q

Vinblastine

  1. class of MT inhibitor?
  2. MOA?
  3. clinical uses?
  4. toxicity?
A
  1. vinca alkaloid
  2. prevents polymerization
  3. testicular cancer, hodgkin’s lymphoma
  4. myelosuppression, N/V
31
Q

Vincristin

  1. class of MT inhibitor?
  2. MOA?
  3. clinical uses?
  4. toxicity?
A
  1. vinca alkaloid
  2. prevents polymerization
  3. childhood ALL (used with glucocorticoids), hodgkin’s lymphoma
  4. dose-limiting neurotoxicity (peripheral neuropathy), low toxicity at bone marrow
32
Q

Resistance seen in vinca alkaloids?

A
  1. amplification of P-glycoprotein

2. mutations at tubulin binding

33
Q

Paclitaxel

  1. class of MT inhibitor?
  2. MOA?
  3. clinical uses?
A
  1. taxanes
  2. prevent depolymerization of microtubules
  3. metastatic breast cancer, ovarian, lung, head and neck cancers (incld. glioblastomas)
34
Q

Docetaxel

  1. class of MT inhibitor?
  2. MOA?
  3. clinical uses?
A
  1. taxanes
  2. prevent depolymerization of microtubules
  3. metastatic breast cancer, ovarian, lung, head and neck, HORMONE REFRACTORY PROSTATE CANCER
35
Q

toxicities seen in taxanes?

A

neutropenia

peripheral neuropathy

hypersensitivity

36
Q

what are the two classes of topoisomerase inhibitors?

A
  1. epipodophyllotoxins - double strand break, topoII

2. camptothecin analog - single strand break, topoI

37
Q

Etoposide?

  1. class of topoisomerase inhibitor?
  2. therapeutic uses?
A
  1. epipodophyllotoxins/topoII

2. broad clinical spectrum; testicular cancer, lung caner, non-hodgkin’s lymphoma

38
Q

Teniposide

  1. class of topoisomerase inhibitor?
  2. therapeutic uses?
A
  1. epipodophyllotoxins

2. A.L.L

39
Q

toxicities seen in epipodophyllotoxins?

A

dose-limiting myelosuppression (neutropenia), oral mucositis

40
Q

Irinotecan

  1. class of topoisomerase inhibitor?
  2. therapeutic uses?
A
  1. camptothecin

2. advanced colorectal cancer

41
Q

Toptecan

  1. class of topoisomerase inhibitor?
  2. therapeutic uses?
A
  1. camptothecin

2. ovarian and lung cancer

42
Q

toxicities seen in camptothecin?

A

severe neutropenia and severe diarrhea

43
Q

main category Rx to treat lymphomas and leukemias?

MOA?

A
  1. glucocorticoids

2. cytotoxic effects/inhibit mitosis at lymphocytes

44
Q

Therapeutic uses for Prednisone?

A
  1. Produce remission in ALL with vincristin

2. Hodgkin’s (MOPP) and Non-hodgkin’s lymphoma (CHOP)

45
Q

Therapeutic use for Dexamethasone?

A

Reduce edema following radiation therapy for brain tumors

46
Q

The mainstay of prostate cancer treatment is ____ deprivation

A

androgen

47
Q

What are the two classes of drugs in prostate cancer treatment?

A
  1. GnRH analogs

2. Androgen-receptor (AR) blockers

48
Q

Leuprolide and Goserelin

  1. class of androgen deprivation therapy?
  2. MOA?
  3. PEARLS?
A
  1. GnRH
  2. inhibit release of FSH, LH so less testosterone production
  3. does NOT inhibit adrenal androgen production
49
Q

Flutamide, Bicalutamide

  1. class of androgen deprivation therapy?
  2. MOA?
A
  1. androgen-receptor blockers

2. competes with natural testosterone at receptor, prevents action of testosterone at prostate cancer cells

50
Q

3 classes of drugs used in anti-estrogen therapy for breast cancer?

A
  1. Selective Estrogen-Receptor Modulators (SERMs)
  2. Selective Estrogen-Receptor Downregulators (SERDs)
  3. Aromatase Inhibitors (AIs)
51
Q

Tamoxifen

  1. class of anti-estrogen therapy?
  2. therapeutic uses?
  3. toxicity?
A
  1. SERMs
  2. ER-positive breast cancer, metastatic breast cancer, prevention in high-risk women
  3. hot flashes, hair loss, N/V, INCREASED RISK OF UTERINE/ENDOMETRIAL CANCER, thromboembolism
52
Q

Fulvestrant

  1. class of anti-estrogen therapy?
  2. therapeutic uses?
  3. PEARLS?
A
  1. SERDs
  2. ER-positive breast cancer in post-menopausal women
  3. binds to ER w/ 100x affinity over Tamoxifen, reduces ER expression
53
Q

Anastrozole, Letrozole, Exemestane

  1. class of anti-estrogen therapy?
  2. therapeutic uses?
  3. PEARLS?
  4. which ones are steroidal vs. non-steroidal?
A
  1. aromatase inhibitors
  2. early and advanced stage breast cancer
  3. first-line therapy for post-menopausal ER+ breast cancer
  4. Anastrozole & Letrozole - nonsteroidal, bind reversibly

Exemestane - steroidal, binds irreversibly

Pharmacology Unit 1 (5 decks)

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