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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
Mitoxantrone 1. class of DNA intercalating agent? 2. clinical uses? 3. PEARL?
1. anthracycline 2. AML remission w/ cytarabine 3. least cardiotoxic
26
Toxicity seen in anthracyclines?
dose-limiting cardiotoxicity (cardiomyopathy) neutropenia stomatitis alopecia
27
Resistance seen in anthracyclines?
P-glycoprotein increased glutathione peroxidase and/or catalase increased DNA repair
28
Bleomycin 1. Class? 2. MOA? 3. Clinical uses? 4. Toxicity?
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
2 classes of microtubule inhibitors? when do they act?
1. Vinca alkaloids 2. Taxanes 3. causes mitotic arrest at M phase
30
Vinblastine 1. class of MT inhibitor? 2. MOA? 3. clinical uses? 4. toxicity?
1. vinca alkaloid 2. prevents polymerization 3. testicular cancer, hodgkin's lymphoma 4. myelosuppression, N/V
31
Vincristin 1. class of MT inhibitor? 2. MOA? 3. clinical uses? 4. toxicity?
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
Resistance seen in vinca alkaloids?
1. amplification of P-glycoprotein | 2. mutations at tubulin binding
33
Paclitaxel 1. class of MT inhibitor? 2. MOA? 3. clinical uses?
1. taxanes 2. prevent depolymerization of microtubules 3. metastatic breast cancer, ovarian, lung, head and neck cancers (incld. glioblastomas)
34
Docetaxel 1. class of MT inhibitor? 2. MOA? 3. clinical uses?
1. taxanes 2. prevent depolymerization of microtubules 3. metastatic breast cancer, ovarian, lung, head and neck, HORMONE REFRACTORY PROSTATE CANCER
35
toxicities seen in taxanes?
neutropenia peripheral neuropathy hypersensitivity
36
what are the two classes of topoisomerase inhibitors?
1. epipodophyllotoxins - double strand break, topoII | 2. camptothecin analog - single strand break, topoI
37
Etoposide? 1. class of topoisomerase inhibitor? 2. therapeutic uses?
1. epipodophyllotoxins/topoII | 2. broad clinical spectrum; testicular cancer, lung caner, non-hodgkin's lymphoma
38
Teniposide 1. class of topoisomerase inhibitor? 2. therapeutic uses?
1. epipodophyllotoxins | 2. A.L.L
39
toxicities seen in epipodophyllotoxins?
dose-limiting myelosuppression (neutropenia), oral mucositis
40
Irinotecan 1. class of topoisomerase inhibitor? 2. therapeutic uses?
1. camptothecin | 2. advanced colorectal cancer
41
Toptecan 1. class of topoisomerase inhibitor? 2. therapeutic uses?
1. camptothecin | 2. ovarian and lung cancer
42
toxicities seen in camptothecin?
severe neutropenia and severe diarrhea
43
main category Rx to treat lymphomas and leukemias? MOA?
1. glucocorticoids | 2. cytotoxic effects/inhibit mitosis at lymphocytes
44
Therapeutic uses for Prednisone?
1. Produce remission in ALL with vincristin | 2. Hodgkin's (MOPP) and Non-hodgkin's lymphoma (CHOP)
45
Therapeutic use for Dexamethasone?
Reduce edema following radiation therapy for brain tumors
46
The mainstay of prostate cancer treatment is ____ deprivation
androgen
47
What are the two classes of drugs in prostate cancer treatment?
1. GnRH analogs | 2. Androgen-receptor (AR) blockers
48
Leuprolide and Goserelin 1. class of androgen deprivation therapy? 2. MOA? 3. PEARLS?
1. GnRH 2. inhibit release of FSH, LH so less testosterone production 3. does NOT inhibit adrenal androgen production
49
Flutamide, Bicalutamide 1. class of androgen deprivation therapy? 2. MOA?
1. androgen-receptor blockers | 2. competes with natural testosterone at receptor, prevents action of testosterone at prostate cancer cells
50
3 classes of drugs used in anti-estrogen therapy for breast cancer?
1. Selective Estrogen-Receptor Modulators (SERMs) 2. Selective Estrogen-Receptor Downregulators (SERDs) 3. Aromatase Inhibitors (AIs)
51
Tamoxifen 1. class of anti-estrogen therapy? 2. therapeutic uses? 3. toxicity?
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
Fulvestrant 1. class of anti-estrogen therapy? 2. therapeutic uses? 3. PEARLS?
1. SERDs 2. ER-positive breast cancer in post-menopausal women 3. binds to ER w/ 100x affinity over Tamoxifen, reduces ER expression
53
Anastrozole, Letrozole, Exemestane 1. class of anti-estrogen therapy? 2. therapeutic uses? 3. PEARLS? 4. which ones are steroidal vs. non-steroidal?
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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