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CMD Block 2 > Sweatman Cytotoxic Chemotherapeutics > Flashcards

Sweatman Cytotoxic Chemotherapeutics Flashcards

1
Q

Anticancer agent that acts on tumor stem cells when they are in the cell cycle and also when they are in the resting phase

A

Cell cycle non specific drug (CCNS)

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2
Q

Anticancer agent that only acts on a cell in the cell cycle and not when they are in the resting phase (G0)

A

Cell cycle specific drug (CCS)

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3
Q

Concept in cancer chemotherapy that a drug will kill a fixed proportion of cells and not a fixed number of tumor cells

A

Log-kill hypothesis

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4
Q

Drug that suppresses formation of mature blood cells: erythrocytes, leukocytes, platelets

A

Myelosuppressant

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5
Q

Mutated form of a normal gene found in tumor cells that makes normal cells act like cancer cells

A

Oncogene

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6
Q

Administering endogenous metabolites to counteract the effects of anticancer drug on non-cancerous cells

A

Rescue therapy

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7
Q

A drug that causes blisters on contact with skin. Can be especially damaging given to veins in large amount.
(ex. alkylating agent, methylchorethamine)

A

Vesicant

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8
Q

Mechanisms of anticancer drug resistance

A

!. Increases in DNA repair

  1. Formation of trapping agents
  2. Changes in the target enzyme
  3. Decreased activation of prodrugs
  4. Inactivation of anticancer drugs
  5. Decreased drug accumulation
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9
Q

Alkylating agents are ____ drugs

A

CCNS

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10
Q

Cytotoxic drugs act with _____ order kinetics

A

First order

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11
Q

How do alkylating agents work?

A
  • form ROS that alkylate nucleophilic groups on DNA bases (esp N7 guanine)
  • leads to cross linking of bases, abnormal base pairing and ultimately DNA breakage
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12
Q

Resistance to alkylating agents

A
  • increased DNA repair
  • decrease drug permeability
  • trapping agents
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13
Q

Cyclophosphamide pharmakokinetics

A
  • alkylating agent
  • action is mediated by CYP450s
  • one of the metabolites is acrolein
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14
Q

Cyclophosphamide clinical uses

A
  • non Hodgkins lymphomas
  • breast and ovarian cancer
  • neuroblastomas
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15
Q

Mechlorethamine pharmakokinetics

A
  • alkylating agent

- spontaneously converts to toxic product

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16
Q

Mechlorethamine clinical use

A

for Hodgkins lymphoma

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17
Q

Toxicity of Cyclophosphamide

A

mainly GI distress, myelosuppression, alopecia (which are pretty much in common with all of these drugs)

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18
Q

Mechlorethamine toxicity

A

mainly GI distress, myelosuppression, alopecia, sterility

- known vesicant action

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19
Q

Platinum analogs include:

A

These are alkylating agents

- include cisplatin, carboplatin, oxaliplatin

20
Q

Platinum analog PK’s

A
  • IV administration

- cleared in unchanged form by kidney

21
Q

Platinum analog clinical uses

A
  • CIsplatin/Carboplatin for testicular carcinoma, bladder, lung, ovarian cancer
  • Oxaliplatin used for advanced colon cancer
22
Q

Platinum analog toxicity

A
  • Cisplatin: hematotoxic, neurotoxic, nephrotoxic
  • Carboplatin: less nephroxitc, hearing loss, myelosuppresant
  • Oxaliplatin: dose-limiting neurotoxicity
23
Q

Procarbazine

A
  • alkylating agent
  • forms H2O2 –> DNA damage
  • penetrates CSF
  • hepatic metabolism
  • used for Hodgkins lymphoma
  • inhibits many enzymes (including MAO)
  • leukmogenic
24
Q

Methotrexate is a _______

A
  • folic acid antagonist
25
Q

Mercaptopurine is a _______

A
  • purine antagonist
26
Q

Thioguanine is a _______

A
  • purine antagonist
27
Q

Fluorouracil is a _______

A
  • pyrimidine antagonist
28
Q

Cytarabine is a _______

A
  • pyrimidine antagonist
29
Q

Gemcitibine is a _______

A
  • pyrimidine antagonist
30
Q

Antimetabolites are _____ drugs acting specifically on ________

A

CCS, S phase

31
Q

methotrexate PK’s

A
  • not metabolized, so clearance depends on renal function
  • doesn’t distribute to CNS
  • pt must be adequately hydrated to prevent renal crystallization
32
Q

Methotrexate clinical uses

A
  • choriocarcinomas
  • acute leukemias
  • non Hodgkins lymphoma
  • cutaneous T lymphomas
  • breast cancer
  • rheumatoid arthritis psoriasis
  • used as an aborticant
33
Q

Methotrexate toxicity

A
  • bone marrow suppression, GI mucosa damage
  • long term causes hepatotoxicity, pulmonary infiltrates or fibrosis
  • can be reduced by giving folinic acid (leukovorin rescue)
34
Q

Mercaptopurine and Thioguanine

A
  • activated by HGPRTases
  • inactivated by alkaline phosphatases
  • low oral bioavailability
  • used for acute leukemias and chronic myelocytic leukemia
  • bone marrow suppression, hepatotoxicity
35
Q

Fluorouracil

A
  • inhibits thymidinylate synthase activity
  • bladder, breast, head, neck, colon, liver, ovarian cancer
  • topically for keratoses and superficial basal cell carcinoma
36
Q

Cytarabine

A
  • pyrimidine antimetabolite

- activated by kinases to AraCTP

37
Q

Gemcitabine

A
  • deoxycitidine analog
  • reduces dNTPs available for DNA synthesis
  • pancreatic cancer, non-small-cell lung cancer, bladder cancer, non-Hodgkin’s lymphoma
  • neutropenia and pulmonary toxicity
38
Q

Plant alkaloids are _____ drugs

A

CCS

39
Q

Vinblastine, Vincristine, Vinorelbine (aka vinca alkaloids)

A
  • plant alkaloids
  • block formation of mitotic spindle
  • given parenterally
  • cleared by biliary excretion
  • acute leukemias, lymphomas, WIlms’ Tumor, choriocarcinoma….
40
Q

Etoposide and Teniposide

A
  • plant alkaloids
  • increase DNA degradation by interacting with Topoisomerase II and inhibiting electron transport
  • lung, prostate, testicular cancer
41
Q

Topotecan and Irinotecan

A
  • plant alkaloids
  • inhibit topoisomerase I –> damage DNA
  • topotecan for advance ovarian cancer and small cell lung cancer
  • irinotecan for metastatic colorectal cancer
  • can cause diarrhea!
42
Q

Pacetaxel and Docetexal

A
  • plant alkaloids
  • prevent microtubule disassembly
  • given IV
  • for advanced breast and ovarian cancer
  • neutropenia, thrombocytopenia, neuropathy, hypersensitivity
43
Q

Doxorubicin and Daunorubicin

A
  • antibiotics
  • anthracyclines, are CCNS drugs
  • inhibit Topo II
  • Hodgkin’s lymphoma, myeloma, sarcoma, breast, endometrial, lung, ovarian, thyroid cancers
  • cardiotoxicity (can give dexrazoxane)
44
Q

Bleomycin

A
  • antibiotics
  • glycopeptides that mess up DNA
  • given parenterally
  • inactivated by tissue amino peptidases
  • Hodgkin’s lymphoma, testicular cancer
  • pulmonar reaction, hypersensitivity, mucucutaneous reactions
45
Q

Dactinomycin

A
  • antibiotic
  • CCNS drug
  • inhibitis DNA dependent RNA synthesis
  • melanoma and WIlm’s tumor
46
Q

Mitomycin

A
  • antibiotic
  • CCNS
  • crosslinks DNA
  • acts against hypoxic cells against adenocarcinomas of lung, stomach, cervix, pancreas

CMD Block 2 (38 decks)

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