CABCO Drugs Flashcards
1
Q
Toxicities due to Bleomycin
A
pulmonary fibrosis (dose dependent)
2
Q
Toxicities due to Cisplatin
A
peripheral neuropathy, ototoxicity, nephrotoxicity
3
Q
Toxicities due to Taxanes (like Taxol)
A
peripheral neuropathy
4
Q
Toxicities due to Vincas (like Vincristine)
A
peripheral neuropathy and GI neuropathy
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
6
Q
What drug blocks IDO?
A
Epacadostat
7
Q
What drug(s) target ABL mutations?
A
Imatinib or dasatinib
8
Q
What drug(s) target Jak-2 mutations?
A
Ruxolitinib
9
Q
What drug(s) target PDGF-R mutations?
A
Imatinib or dasatinib
10
Q
What drug combination therapy is used to treat non-Hodgkin’s lymphoma?
A
CHOP
Cyclophosphamide
Hydroxydanurubicin (doxorubicin)
Oncovin (vincristine)
Prednisone
11
Q
What drug combination therapy is used to treat Hodgkin’s lymphoma?
A
ABVD
Adriamycin (doxorubicin)
Bleomycin
Vinblastine
Dacarbazine
12
Q
What drugs are part of Multi-Drug Resistance (MDR) pumps?
A
Doxorubicin Vincristine Methotrexate Mephalan Cisplatin
DVM MC
13
Q
What drug(s) causes hemorrhagic cystitis?
A
Cyclophosphamide
14
Q
What drug(s) cause neurotoxicity/peripheral neuropathy?
A
Vincristine, Paclitaxel, Cisplatin
15
Q
What drug(s) cause cardiotoxicity?
A
Doxorubicin
16
Q
What drug(s) cause pulmonary fibrosis?
A
Bleomycin
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
18
Q
Toxicities of cyclophosphamide?
A
Hemorrhagic cystitis (bladder), myelosuppression, secondary malignancies
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
20
Q
Toxicities of Cisplatin?
A
Renal (cumulative, major dose-limiting toxicity), peripheral neuropathy, ototoxicity
Causes minimal myelosuppression!
21
Q
Bleomycin mechanism of action? Targeted/cytotoxic/immuno therapy?
A
Binds DNA and generates free radicals that cause breaks in DNA
Cytotoxic
22
Q
Bleomycin toxicities?
A
Pulmonary fibrosis, minimal myelosuppression
23
Q
What drug is a topoisomerase I inhibitor?
A
Topotecan
24
Q
What drugs are topoisomerase II inhibitors?
A
Etopside and doxorubicin
25
Topotecan: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?
Traps Topoisomerase I-DNA complex resulting in formation of SS DNA breaks
S phase specific action
Cytotoxic
26
Toxicities of Topotecan?
Myelosuppression
27
Doxorubicin and Etopside: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?
Traps topoisomerase II-DNA complex resulting in the formation of DS DNA breaks
S-phase specific
Cytotoxic
28
Toxicities of Doxorubicin and Etoposide?
Both cause myelosuppression
Doxorubicin cause cardiotoxicity (dose-related/cumulative)
29
What are two microtubule targeted drugs?
Vincristine and Paclitaxel
30
Vincristine and Paclitaxel: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?
Binds tubulin and blocks mitosis (Vincristine binds to the + end and Pacitaxel binds to the - end)
M-phase specific
Cytotoxic
31
Toxicities of vincristine and paclitaxel?
Both cause peripheral neuropathy
Paclitaxel causes myelosuppression, vincristine causes minimal myelosuppression
32
Methotrexate: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?
Inhibits dihydrofolate reductase -> folate pathway imp. for synthesis of thymidine and purines; blocks DNA synthesis
S-phase specific
Cytotoxic
33
Toxicities of methotrexate?
Nephrotoxicity, myelosuppression, mucositis
34
5-fluorouracil: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?
Thymidine analogue; prodrug that requires activation to inhibit the synthesis of thymidine by thymidylate synthase (blocks DNA synthesis)
S-phase specific
Cytotoxic
35
Toxicities of 5-fluorouracil?
Myelosuppression and mucositis
36
Cytosine Arabinoside: mechanism of action, specific/nonspecific cell cycle action, targeted/cytotoxic/immuno therapy?
Nucleoside analog that requires activation to inhibit DNA polymerase and thus ultimately DNA synthesis
S-phase specific
Cytotoxic
37
Toxicities of Cytosine Arabinoside (Ara-C)?
Myelosuppression + high-doses associated with cerebellar toxicity
38
Three antimetabolites?
Methotrexate, 5-Fluorouracil, Cytosine Arabinoside
39
What is Rituximab? Indicated uses?
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
What is Trastuzumab? Indicated uses?
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
Three ways Anti-CD antibodies (aka Rituximab) kill cells?
complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and direct lysis
42
What is Sipuleucel-T?
A dendritic cell vaccine for metastatic castration-resistant prostate cancer
Contains prostatic acid phosphatase (tumor antigen) + GM-CSF to stimulate APC maturation
43
What is Talimogene Iaherparepvec (T-VEC)?
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
What does Ipilimumab do?
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
What are the two PD-1 immune checkpoint inhibitors?
Pembrolizumab and Nivolumab
They bind to PDL1 on cancer cells and inhibit t cell response
46
What is Atezolizumab?
PD-L1 immune checkpoint inhibitor
47
What is Tisagenlecleucel/ CTL019? Treatment indications?
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
What is Axicabtagene ciloucel? Treatment indications?
CAR-T cell therapy
Used to treat relapsed large B-cell lymphomas
49
Toxicities of CAR-T cell therapies?
Cytokine release syndrome, neurotoxicity (cerebral edema), acute kidney injury, increased risk of infections (due to killing of normal B cells)
50
Symptoms of Cytokine Release Syndrome? How do you manage it clinically?
Dangerously high fever & precipitous drop in blood pressure
Treat with steroids and Toclizumab (anti-IL 6 antibodies)
51
What are the three EGFR targeting agents?
Erlotinib
Trastuzumab
Cetuximab
ETC!
52
Erlotinib/Tarceva: mechanism of action, treatment indications?
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
Trastuzumab/Herceptin: mechanism of action, treatment indications?
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
Cetuximab: mechanism of action, treatment indications?
EGFR targeting antibody
Used to treat colon cancer
Obviously does not work if the mutation is downstream of the receptor
55
Imatinib/Gleevec: mechanism of action? Treatment indications?
Inhibits BCR-ABL tyrosine kinase present in Ph+ CML (this signal normally promotes cell proliferation and survival)
56
60-90% of CML relapses are associated with mutations in the BCR-ABL _______ domain
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
Vemurafenib: mechanism of action? Treatment indications?
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
Bevacizumab: mechanism of action? Treatment indications?
Monoclonal antibody against VEGF (vascular endothelial growth factor); prevents interaction of VEGF with its receptor
Angiogenesis inhibitor
Used to treat non-squamous NSCLC
59
What else does Bevacizumab treat?
Macular degeneration and diabetic retinopathy
60
Sunitnib: mechanism of action? Treatment indications?
Inhibits tyrosine kinase activity of VEGF receptors as well as PDGFR and c-KIT
Angiogenesis inhibitor
61
Azathioprine/Imuran: use, administration, and (basic) mechanism
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
Azathioprine toxicities?
Bone marrow suppression and hepatic insufficiency
63
Briefly describe the interaction between allopurinol and Azathioprine
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
What is an acute toxic effect of bleomycin? What symptoms indicate that this reaction is occurring?
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
Use of inhaled oxygen during or after bleomycin therapy can increase the risk of what two conditions?
Interstitial pneumonitis or pulmonary fibrosis
Oxygen should be given only if absolutely necessary and in the minimal concentration needed
66
What are the earliest symptoms associated with Bleomycin pulmonary toxicity?
Dyspnea and cough
| Note: Chest x-ray can lag behind the development of symptoms
67
What metabolite is responsible for hemorrhagic cystitis after Cylophosphamide use?
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
How do you prevent cyclophosphamide induced hemorrhagic cystitis?
Aggressive hydration with oral and IV fluids or Mesna (a drug that detoxifies the active metabolites)
69
Cytosine Arabinoside toxicity is most likely to occur in what population?
Elderly patients with renal or hepatic insufficiency
70
When prescribing Cisplatin you should avoid concurrent use of other ________ drugs?
Nephrotoxic
The dose-limiting toxicity of Cisplatin is nephrotoxicity. Repeated administration leads to renal tubular necrosis and chronic renal problems
71
What are the acute adverse effects of Paclitaxel?
Acute hypersensitivity
Mild flushing, hypotension, bronchospasm with dyspnea, and urticaria
Usually within first second to first 10 mins of infusion
72
What are three estrogen inhibitors?
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
What estrogen inhibitor can actually prevent breast cancer?
Tamoxifen
74
Four CD20 targeted monoclonal antibodies?
1. Rituximab
2. Ibritumomab
3. Tositumomab
4. Ofatumomab
75
Benefits of radioimmunotherapy with monoclonal antibodies?
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
What is TDM1?
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
First two drugs we use once Imatinib stops working?
Dasatinib and Nilotinib
78
Pemetrexed: drug class and treatment indication
Antimetabolite used to treat non-squamous NSCLC
79
Afatinib: drug class and treatment indication
Targets EGFR mutations; second line of therapy of squamous cell carcinoma, regardless of EGFR mutation status
