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MS1 Spring > CABCO Drugs > Flashcards

CABCO Drugs Flashcards

1
Q

Toxicities due to Bleomycin

A

pulmonary fibrosis (dose dependent)

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2
Q

Toxicities due to Cisplatin

A

peripheral neuropathy, ototoxicity, nephrotoxicity

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3
Q

Toxicities due to Taxanes (like Taxol)

A

peripheral neuropathy

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4
Q

Toxicities due to Vincas (like Vincristine)

A

peripheral neuropathy and GI neuropathy

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5
Q

Mechanism of action of Herceptin (Traztuzumab)?

A

Monoclonal antibody that binds to the Her2/neu receptor on tumor cells. This blocks the receptor and allows NK cells to locate the tumor cell and induce apoptosis

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6
Q

What drug blocks IDO?

A

Epacadostat

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7
Q

What drug(s) target ABL mutations?

A

Imatinib or dasatinib

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8
Q

What drug(s) target Jak-2 mutations?

A

Ruxolitinib

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9
Q

What drug(s) target PDGF-R mutations?

A

Imatinib or dasatinib

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10
Q

What drug combination therapy is used to treat non-Hodgkin’s lymphoma?

A

CHOP

Cyclophosphamide
Hydroxydanurubicin (doxorubicin)
Oncovin (vincristine)
Prednisone

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11
Q

What drug combination therapy is used to treat Hodgkin’s lymphoma?

A

ABVD

Adriamycin (doxorubicin)
Bleomycin
Vinblastine
Dacarbazine

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12
Q

What drugs are part of Multi-Drug Resistance (MDR) pumps?

A 
Doxorubicin
Vincristine
Methotrexate
Mephalan
Cisplatin

DVM MC

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13
Q

What drug(s) causes hemorrhagic cystitis?

A

Cyclophosphamide

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14
Q

What drug(s) cause neurotoxicity/peripheral neuropathy?

A

Vincristine, Paclitaxel, Cisplatin

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15
Q

What drug(s) cause cardiotoxicity?

A

Doxorubicin

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16
Q

What drug(s) cause pulmonary fibrosis?

A

Bleomycin

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17
Q

Cyclophosphamide: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?

A

DNA alkylating agent that cross-links DNA and blocks DNA replication

Nonspecific cell cycle action

Cytotoxic

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18
Q

Toxicities of cyclophosphamide?

A

Hemorrhagic cystitis (bladder), myelosuppression, secondary malignancies

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19
Q

Cisplatin: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?

A

Crosslinks DNA by a different mechanism than cyclophosphamide

Nonspecific cell cycle action

Cytotoxic

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20
Q

Toxicities of Cisplatin?

A

Renal (cumulative, major dose-limiting toxicity), peripheral neuropathy, ototoxicity

Causes minimal myelosuppression!

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21
Q

Bleomycin mechanism of action? Targeted/cytotoxic/immuno therapy?

A

Binds DNA and generates free radicals that cause breaks in DNA

Cytotoxic

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22
Q

Bleomycin toxicities?

A

Pulmonary fibrosis, minimal myelosuppression

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23
Q

What drug is a topoisomerase I inhibitor?

A

Topotecan

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24
Q

What drugs are topoisomerase II inhibitors?

A

Etopside and doxorubicin

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25
Q

Topotecan: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?

A

Traps Topoisomerase I-DNA complex resulting in formation of SS DNA breaks

S phase specific action

Cytotoxic

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26
Q

Toxicities of Topotecan?

A

Myelosuppression

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27
Q

Doxorubicin and Etopside: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?

A

Traps topoisomerase II-DNA complex resulting in the formation of DS DNA breaks

S-phase specific

Cytotoxic

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28
Q

Toxicities of Doxorubicin and Etoposide?

A

Both cause myelosuppression

Doxorubicin cause cardiotoxicity (dose-related/cumulative)

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29
Q

What are two microtubule targeted drugs?

A

Vincristine and Paclitaxel

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30
Q

Vincristine and Paclitaxel: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?

A

Binds tubulin and blocks mitosis (Vincristine binds to the + end and Pacitaxel binds to the - end)

M-phase specific

Cytotoxic

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31
Q

Toxicities of vincristine and paclitaxel?

A

Both cause peripheral neuropathy

Paclitaxel causes myelosuppression, vincristine causes minimal myelosuppression

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32
Q

Methotrexate: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?

A

Inhibits dihydrofolate reductase -> folate pathway imp. for synthesis of thymidine and purines; blocks DNA synthesis

S-phase specific

Cytotoxic

33
Q

Toxicities of methotrexate?

A

Nephrotoxicity, myelosuppression, mucositis

34
Q

5-fluorouracil: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?

A

Thymidine analogue; prodrug that requires activation to inhibit the synthesis of thymidine by thymidylate synthase (blocks DNA synthesis)

S-phase specific

Cytotoxic

35
Q

Toxicities of 5-fluorouracil?

A

Myelosuppression and mucositis

36
Q

Cytosine Arabinoside: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?

A

Nucleoside analog that requires activation to inhibit DNA polymerase and thus ultimately DNA synthesis

S-phase specific

Cytotoxic

37
Q

Toxicities of Cytosine Arabinoside (Ara-C)?

A

Myelosuppression + high-doses associated with cerebellar toxicity

38
Q

Three antimetabolites?

A

Methotrexate, 5-Fluorouracil, Cytosine Arabinoside

39
Q

What is Rituximab? Indicated uses?

A

Anti-CD20 chimeric monoclonal antibody

Basically targets and kills all B cells because all B cells have CD20

Used in refractory B-cell malignancies like non-Hodgkin’s lymphoma and autoimmune diseases like rheumatoid arthritis

40
Q

What is Trastuzumab? Indicated uses?

A

Anti-ERBB2 (HER2/neu) humanized monoclonal antibody

Inhibits oncogenic signaling pathways downstream of ERBB2 in HER2-overexpressing breast cancer and HER2-overexpressing tumors (i.e. metastatic gastric cancer)

41
Q

Three ways Anti-CD antibodies (aka Rituximab) kill cells?

A

complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and direct lysis

42
Q

What is Sipuleucel-T?

A

A dendritic cell vaccine for metastatic castration-resistant prostate cancer

Contains prostatic acid phosphatase (tumor antigen) + GM-CSF to stimulate APC maturation

43
Q

What is Talimogene Iaherparepvec (T-VEC)?

A

An engineered oncolytic virus for unresectable melanoma; administered intratumorally

T-VEC can infect a range of cells but only replicates in tumor cells. This replication has a direct therapeutic effect through lysis of the host cell, and an indirect therapeutic effect through liberation of tumor antigens and activation of the immune system

44
Q

What does Ipilimumab do?

A

It’s the first immune checkpoint inhibitor approved by the FDA for stage IV melanoma

Binds to B7 and stops CTLA4 on activated T-cells from binding

45
Q

What are the two PD-1 immune checkpoint inhibitors?

A

Pembrolizumab and Nivolumab

They bind to PDL1 on cancer cells and inhibit t cell response

46
Q

What is Atezolizumab?

A

PD-L1 immune checkpoint inhibitor

47
Q

What is Tisagenlecleucel/ CTL019? Treatment indications?

A

CAR-T cell therapy

Patient’s own t-cells are genetically modified to recognize and destroy CD19-expressing cells. CD19 is present on both normal and malignant B cells

Used to treat pediatric relapsed refractory acute lymphoblastic leukemia (ALL)

48
Q

What is Axicabtagene ciloucel? Treatment indications?

A

CAR-T cell therapy

Used to treat relapsed large B-cell lymphomas

49
Q

Toxicities of CAR-T cell therapies?

A

Cytokine release syndrome, neurotoxicity (cerebral edema), acute kidney injury, increased risk of infections (due to killing of normal B cells)

50
Q

Symptoms of Cytokine Release Syndrome? How do you manage it clinically?

A

Dangerously high fever & precipitous drop in blood pressure

Treat with steroids and Toclizumab (anti-IL 6 antibodies)

51
Q

What are the three EGFR targeting agents?

A

Erlotinib
Trastuzumab
Cetuximab

ETC!

52
Q

Erlotinib/Tarceva: mechanism of action, treatment indications?

A

Inhibitor of EGFR tyrosine kinase (blocks EGFR signaling pathways involved in tumor cell proliferation, metastasis, angiogenesis and survival). Intracellular action!

Useful in treatment of non-small cell lung cancer in patients with activating mutations in EGFR tyrosine kinase

53
Q

Trastuzumab/Herceptin: mechanism of action, treatment indications?

A

Humanized monoclonal antibody to HER-2/neu receptor

Works by preventing receptor signaling by inhibiting receptor dimerization/processing or by down-regulation of receptor

Promotes cell-mediated cytotoxicity & antibody-dependent cell-mediated cytotoxicity

Obviously does not work if the mutation is downstream of the receptor

54
Q

Cetuximab: mechanism of action, treatment indications?

A

EGFR targeting antibody

Used to treat colon cancer

Obviously does not work if the mutation is downstream of the receptor

55
Q

Imatinib/Gleevec: mechanism of action? Treatment indications?

A

Inhibits BCR-ABL tyrosine kinase present in Ph+ CML (this signal normally promotes cell proliferation and survival)

56
Q

60-90% of CML relapses are associated with mutations in the BCR-ABL _______ domain

A

Kinase domain

This reduces drug binding and maintains the kinase in the active state

This is overcome by targeting multiple regions of the BCR-ABL kinase to circumvent drug resistance

57
Q

Vemurafenib: mechanism of action? Treatment indications?

A

Blocks the activity of constituitively activated BRAF (has mutation in V600E) but NOT normal BRAF

Used to treat late-stage melanomas + hairy cell leukemia (investigational use)

58
Q

Bevacizumab: mechanism of action? Treatment indications?

A

Monoclonal antibody against VEGF (vascular endothelial growth factor); prevents interaction of VEGF with its receptor

Angiogenesis inhibitor

Used to treat non-squamous NSCLC

59
Q

What else does Bevacizumab treat?

A

Macular degeneration and diabetic retinopathy

60
Q

Sunitnib: mechanism of action? Treatment indications?

A

Inhibits tyrosine kinase activity of VEGF receptors as well as PDGFR and c-KIT

Angiogenesis inhibitor

61
Q

Azathioprine/Imuran: use, administration, and (basic) mechanism

A

Oral & IV immunosuppressive agent that is used in transplant patients and in the treatment of autoimmune disorders such as rheumatoid arthritis and lupus

It’s a chemical analog of the endogenous purines: adenine, guanine, and hypoxanthine

62
Q

Azathioprine toxicities?

A

Bone marrow suppression and hepatic insufficiency

63
Q

Briefly describe the interaction between allopurinol and Azathioprine

A

Azaithoprine is metabolized to 6-mercaptopurine (6-MP). 6-MP is then metabolized to 6-thioiosinic acid, which is an active form that inhibits enzymes necessary for purine synthesis

Rather than 6-MP be “funneled” to the active pathway, Xanthine oxidase can break down 6-MP into an inactive form, 6-thiouric acid. BUT allopurinol inhibits Xanthine Oxidase so all 6-MP is pushed down the active pathway into 6-thioinosinic acid

64
Q

What is an acute toxic effect of bleomycin? What symptoms indicate that this reaction is occurring?

A

Idiosyncratic or anaphylactoid rxn

Rxn consists of hypotension, fever, chills, wheezing, and mental confusion

Note: test dose of less than 2 units of bleomycin is recommended prior to bleomycin treatment

65
Q

Use of inhaled oxygen during or after bleomycin therapy can increase the risk of what two conditions?

A

Interstitial pneumonitis or pulmonary fibrosis

Oxygen should be given only if absolutely necessary and in the minimal concentration needed

66
Q

What are the earliest symptoms associated with Bleomycin pulmonary toxicity?

A

Dyspnea and cough

Note: Chest x-ray can lag behind the development of symptoms

67
Q

What metabolite is responsible for hemorrhagic cystitis after Cylophosphamide use?

A

Acrolein, a toxic irritant to the bladder epithelium

The active form of cyclophosphamide, 4-hydroxycyclophosphamide, tautomerizes to aldophosphamide, which can now freely pass through the cell membrane.

Aldophosphamide is either converted to active metabolites via aldehyde dehydrogenase or is converted to the active metabolites phosphoramide mustard + acrolein

68
Q

How do you prevent cyclophosphamide induced hemorrhagic cystitis?

A

Aggressive hydration with oral and IV fluids or Mesna (a drug that detoxifies the active metabolites)

69
Q

Cytosine Arabinoside toxicity is most likely to occur in what population?

A

Elderly patients with renal or hepatic insufficiency

70
Q

When prescribing Cisplatin you should avoid concurrent use of other ________ drugs?

A

Nephrotoxic

The dose-limiting toxicity of Cisplatin is nephrotoxicity. Repeated administration leads to renal tubular necrosis and chronic renal problems

71
Q

What are the acute adverse effects of Paclitaxel?

A

Acute hypersensitivity

Mild flushing, hypotension, bronchospasm with dyspnea, and urticaria

Usually within first second to first 10 mins of infusion

72
Q

What are three estrogen inhibitors?

A
  1. Tamoxifen: binds to ER and acts as partial agonist/antagonist depending on the organ/tissue
  2. Aromatase inhibitors: block estrogen formation
  3. Fulvestrant: Binds to ER and causes it to self-destruct
73
Q

What estrogen inhibitor can actually prevent breast cancer?

A

Tamoxifen

74
Q

Four CD20 targeted monoclonal antibodies?

A
  1. Rituximab
  2. Ibritumomab
  3. Tositumomab
  4. Ofatumomab
75
Q

Benefits of radioimmunotherapy with monoclonal antibodies?

A

Radioisotope can be delivered directly to the tumor cell and won’t cause greater tissue damage

He gave an example of radioisotope-tagged Ibritumomab (CD20 Moab)

76
Q

What is TDM1?

A

It’s a cytotoxic agent that is attached to a monoclonal antibody via a linker so it will be internalized into a cell with the antibody

Once inside the cell the toxic effects are delivered. This is useful for things like TDM1 that are too nonspecific to be used systemically but are useful when delivered directly into the desired cell

He gave the example of attaching this to Herceptin/Trastuzumab

77
Q

First two drugs we use once Imatinib stops working?

A

Dasatinib and Nilotinib

78
Q

Pemetrexed: drug class and treatment indication

A

Antimetabolite used to treat non-squamous NSCLC

79
Q

Afatinib: drug class and treatment indication

A

Targets EGFR mutations; second line of therapy of squamous cell carcinoma, regardless of EGFR mutation status

MS1 Spring (10 decks)

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