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Hem Onc Drugs Flashcards

1
Q

Methotrexate (MTX) mech:

A

Folic acid analog that inhibits dihydrofolate reductase, which leads to dTMP -> decreased DNA and decreased protein synthesis

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2
Q

Methotrexate Clinical use:

A

Cancers: Leukemias, Lymphomas, Choriocarcinoma, Sarcomas. Non-neoplastic: abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis, IBD

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3
Q

Methotrexate Toxicity:

A

Myelosuppression, which is reverible with leucovorin (folinic acid) ‘rescue’. Macrovesicular fatty change in liver. Mucositis. Teratogen

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4
Q

5-FU Mech:

A

Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid. This complex inhibits thymidylate synthase which leads to a decrease in dTMP,, leading to decrease DNA and protein synthesis

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5
Q

5-FU Clinical Use:

A

Colon cancer, pancreatic cancer, basal cell carcinoma (topical)

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6
Q

5-FU Toxicity:

A

Myelosuppression, which is not reversible with leucovorin. OD: rescue with uridine. Photosensitivity.

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7
Q

Cytarabine mech:

A

pyrimidine analog that inhibits DNA polymerase

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8
Q

Cytarabine Clinical Use:

A

Leukemias, Lymphomas

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9
Q

Cytarabine Toxicity:

A

Leukopenia, thrombocytopenia, megaloblastic anemia, CYTarabine causes panCYTopenia

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10
Q

Azathioprine, 6-mercaptopurine, 6-thioguanine (6-TG) mech:

A

purine (thiol) analogs lead to decreased de novo purine synthesis. Activated by HGPRT

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11
Q

Azathioprine, 6-mercaptopurine, 6-thioguanine (6-TG) Clinical Use:

A

Preventing organ rejection, RA, SLE (azathioprine). Leukemia, IBD (6-MP, 6TG).

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12
Q

Azathioprine, 6-mercaptopurine, 6-thioguanine (6-TG) Toxocity:

A

Bone marrow, GI, liver. Azathioprine and 6-MP are metabolized by xanthine oxidase; thus both have increased toxicity with allopurinol, which inhibits their metabolism.

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13
Q

The antimetabolites inlcude

A

MTX, 5-FU, Cytarabine, Azathioprine/6-MP

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14
Q

What are the antitumor antibiotics?

A

Dactinomycin, Doxorubicin (Adriamycin), Daunorubicin, Bleomycin

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15
Q

Dactinomycin (Actinomycin D) mech:

A

intercalates in DNA

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16
Q

Dactiomycin (Actinomycin D) use:

A

Wilms tumor, Ewing sarcoma, rhabdomyosarcoma. Used for childhood rumors (children act out)

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17
Q

Dactinomycin (Actinomycin D) Toxicity:

A

Myelosuppression

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18
Q

Doxorubicin (Adriamycin), Daunorubicin mech:

A

Generate free radicals. Intercalate in DNA which leads to breaks in DNA and decrease in replication.

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19
Q

Doxorubicin (Adriamycin), Daunorubicin use:

A

Solid tumors, Leukemias, Lymphomas

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20
Q

Doxorubicin (Adriamycin), Daunorubicin Toxicity:

A

Cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia. Toxic to tissues following extravasation. Dexrazoxane (iron chelating agent), used to prevent cardiotoxicity

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21
Q

Bleomycin mech:

A

Induces free radical formation, which causes breaks in DNA strands.

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22
Q

Bleomycin use:

A

Testicular cancer, Hodgkin lymphoma

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23
Q

Bleomycin Toxicity:

A

Pulmonary fibrosis, skin changes, mucositis. Minimal myelosuppression.

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24
Q

What are the alkylating agents?

A

1) Cyclophosphamide/ifosfamide 2) Nitrosoureas: (carmustine, lomustine, semustine, streptozocin) 3) Busulfan

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25
Cyclophosphamide, ifosfamide mech:
Covalently X-linked (interstrand) DNA at guanine N-7. Require bioactivation by liver.
26
Cyclophosphamide, ifosfamide use:
Solid tumors, leukemia, lymphomas, and some brain cancers
27
Cyclophosphamide, ifosfamide toxicity:
Myelosuppression; hemorrhagic cystitis, partially prevented with mesna (thio group of mesna binds toxic metabolites)
28
Nitrosoureas (carmustine, lomustine, semustine, streptozocin) mech:
Require bioactivation. Cross blood-brain barrier to CNS. Cross-Links DNA
29
Nitrosoureas (carmustine, lomustine, semustine, streptozocin) clinical use:
brain tumors (including glioblastoma multiforme)
30
Nitrosoureas (carmustine, lomustine, semustine, streptozocin) toxicity:
CNS toxicity (convulsions, dizziness, ataxia)
31
Busulfan mech:
Cross-links DNA
32
Busulfan clinical use:
CML. Also used to ablate patient's bone marrow before bone marrow transplantation
33
Bustulfan toxicity:
Severe myelosuppression (in almost all cases), pulmonary fibrosis, hyperpigmentation.
34
What are the microtubule inhibitors?
Vincristine/Vinblastine & paclitaxel and other taxols.
35
Vincristine/Vinblastine mech:
Vinca alkaloid that bind beta tubulin, inhibit its polymerization into microtubules, thereby preventing mitotic spindle formation (M-phase arrest)
36
Vincristine/Vinblastine use:
Solid tumors, leukemias, and lymphomas
37
Vincristine/Vinblastine toxicity:
1) Vincristine - neurotoxicity (areflexia, peripheral neuritis), paralytic ileus. 2) Vinblastine blasts bone marrow (suppression)
38
Paclitaxel, other taxols mech
Hyperstabalize polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur). 'It is taxing to stay polymerized'
39
Paclitaxel clinical use
Ovarian and breast carcinomas
40
Paclitaxel toxicity:
Myelosupression, alopecia, hypersensitivity
41
Cisplatin, carboplatin mech:
cross-link DNA
42
Cisplatin, carboplatin use:
Testicular, bladder, ovary, lung carcinoma
43
Cisplatin, carboplatin toxicity:
Nephrotoxicity and acoustic nerve damage. Prevent nephrotoxicity with amifostine (free radial scavenger) and chloride diuresis.
44
Etoposide, teniposide mech:
eTOPOside inhibits TOPOisomerase II which increases DNA degradation.
45
Clinical use of etoposide, teniposide:
Solid tumors (particularily testicular and small cell lung cancer), leukemias, lumphomas.
46
Etopoise, teniposide toxicity:
myelosuppression, GI irritation, alopecia
47
Irinotecan, topotecan mech:
Inhibit topoisomerase I and prevent DNA unwinding and replication
48
Irinotecan, topotecan clinical use:
Colon cancer (irinotecan); ovarian and small cell lug cancers (topotecan)
49
Irinotecan topotecan toxicity:
Severe myelosuppression, diarrhea
50
Hydroxyurea mech:
Inhibits ribonucleotide reductase which leads to decreased DNA Synthesis (S-phase specific)
51
Hydroxyurea use:
Melanoma, CML, sickle cell disease (increased HbF)
52
Hodoxyurea toxicity:
Bone marrow suppression, GI upset
53
Prednisone, prednisolone mech:
may trigger apoptosis. may even work on nondividing cells.
54
prednisone, prednisolone use:
most commonly used glucocorticoid in cancer chemo. used in CLL, non-hodgkin lymphomas (part of combination chemo regimen). Also used as imunosuppressants (i.e autoimmune diseases).
55
Prednisone, prednisolone toxicity:
Cushing-like symptoms; weight gain, central obesity, muscle breakdown ,cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycmia, psychosis
56
Tamoxifen, raloxifene mech
SERMS - receptor antagonists in breast and agonists in bone. Block the binding of estrogen to ER + cells
57
Tamoxifen, raloxifene clinical use
breast cancer treatment (tamoxifen only) and prevention. Raloxifene for osteoporosis.
58
Tamoxifen toxicity
partial agonist in endometrium, which increases the risk of endometrial cancer; 'hot flashes'
59
Raloxifene toxicity
no increase in endometrial carcinoma because it is an endometrial antagonist
60
Trastuzumab (herceptin) mech
monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase receptor. Helps kill breast cancer cells that overexpress HER-2, through inhibition of HER2 initiated cellular signaling and antibody dependent cytotoxicity
61
Trastuzumab (herceptin) clinical use:
HER-2 + breast cancer and gastric cancer (tras2zumab)
62
Trastuzumab toxicity:
Cardiotoxicity. "HEARTceptin' damages the heart
63
Imatinib (Gleevac) mech:
Tyrosine Kinase inhibitor of bcr-abl (Philadelphia chromosome fusion gene in CML) and c-Kit (common in GI stromal tumors)
64
Imatinib use:
CML, GI stromal tumors
65
Imatinib toxicity:
fluid retention
66
Rituximab mech:
monoclonal antibody against CD20, which is found on most B-cell neoplasms
67
Rituximab use:
non-hodgkin lymphoma, rheumatoid arthritis (with MTX); ITP
68
Rituximab toxicity:
increased risk of progressive multifocal leukoencephalopathy
69
Vemurafenib mech:
Small molecule inhibitor to forms of the B-Raf kinase with the V600E mutation
70
Vemurafenib use:
Metastatic melanoma
71
Bevacizumab mech:
monoclonal antibody against VEGF, inhibits angiogenesis
72
Bevacizumab clinical use:
Solid tumors (colorectal cancer, renal cell carcinoma)
73
Bevacizumab toxicity:
Hemorrhage and impaired wound healing

First Aid (33 decks)

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