Flashcards in Hem Onc Drugs Deck (73):
Methotrexate (MTX) mech:
Folic acid analog that inhibits dihydrofolate reductase, which leads to dTMP -> decreased DNA and decreased protein synthesis
Methotrexate Clinical use:
Cancers: Leukemias, Lymphomas, Choriocarcinoma, Sarcomas. Non-neoplastic: abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis, IBD
Myelosuppression, which is reverible with leucovorin (folinic acid) 'rescue'. Macrovesicular fatty change in liver. Mucositis. Teratogen
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
5-FU Clinical Use:
Colon cancer, pancreatic cancer, basal cell carcinoma (topical)
Myelosuppression, which is not reversible with leucovorin. OD: rescue with uridine. Photosensitivity.
pyrimidine analog that inhibits DNA polymerase
Cytarabine Clinical Use:
Leukopenia, thrombocytopenia, megaloblastic anemia, CYTarabine causes panCYTopenia
Azathioprine, 6-mercaptopurine, 6-thioguanine (6-TG) mech:
purine (thiol) analogs lead to decreased de novo purine synthesis. Activated by HGPRT
Azathioprine, 6-mercaptopurine, 6-thioguanine (6-TG) Clinical Use:
Preventing organ rejection, RA, SLE (azathioprine). Leukemia, IBD (6-MP, 6TG).
Azathioprine, 6-mercaptopurine, 6-thioguanine (6-TG) Toxocity:
Bone marrow, GI, liver. Azathioprine and 6-MP are metabolized by xanthine oxidase; thus both have increased toxicity with allopurinol, which inhibits their metabolism.
The antimetabolites inlcude
MTX, 5-FU, Cytarabine, Azathioprine/6-MP
What are the antitumor antibiotics?
Dactinomycin, Doxorubicin (Adriamycin), Daunorubicin, Bleomycin
Dactinomycin (Actinomycin D) mech:
intercalates in DNA
Dactiomycin (Actinomycin D) use:
Wilms tumor, Ewing sarcoma, rhabdomyosarcoma. Used for childhood rumors (children act out)
Dactinomycin (Actinomycin D) Toxicity:
Doxorubicin (Adriamycin), Daunorubicin mech:
Generate free radicals. Intercalate in DNA which leads to breaks in DNA and decrease in replication.
Doxorubicin (Adriamycin), Daunorubicin use:
Solid tumors, Leukemias, Lymphomas
Doxorubicin (Adriamycin), Daunorubicin Toxicity:
Cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia. Toxic to tissues following extravasation. Dexrazoxane (iron chelating agent), used to prevent cardiotoxicity
Induces free radical formation, which causes breaks in DNA strands.
Testicular cancer, Hodgkin lymphoma
Pulmonary fibrosis, skin changes, mucositis. Minimal myelosuppression.
What are the alkylating agents?
1) Cyclophosphamide/ifosfamide 2) Nitrosoureas: (carmustine, lomustine, semustine, streptozocin) 3) Busulfan
Cyclophosphamide, ifosfamide mech:
Covalently X-linked (interstrand) DNA at guanine N-7. Require bioactivation by liver.
Cyclophosphamide, ifosfamide use:
Solid tumors, leukemia, lymphomas, and some brain cancers
Cyclophosphamide, ifosfamide toxicity:
Myelosuppression; hemorrhagic cystitis, partially prevented with mesna (thio group of mesna binds toxic metabolites)
Nitrosoureas (carmustine, lomustine, semustine, streptozocin) mech:
Require bioactivation. Cross blood-brain barrier to CNS. Cross-Links DNA
Nitrosoureas (carmustine, lomustine, semustine, streptozocin) clinical use:
brain tumors (including glioblastoma multiforme)
Nitrosoureas (carmustine, lomustine, semustine, streptozocin) toxicity:
CNS toxicity (convulsions, dizziness, ataxia)
Busulfan clinical use:
CML. Also used to ablate patient's bone marrow before bone marrow transplantation
Severe myelosuppression (in almost all cases), pulmonary fibrosis, hyperpigmentation.
What are the microtubule inhibitors?
Vincristine/Vinblastine & paclitaxel and other taxols.
Vinca alkaloid that bind beta tubulin, inhibit its polymerization into microtubules, thereby preventing mitotic spindle formation (M-phase arrest)
Solid tumors, leukemias, and lymphomas
1) Vincristine - neurotoxicity (areflexia, peripheral neuritis), paralytic ileus. 2) Vinblastine blasts bone marrow (suppression)
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'
Paclitaxel clinical use
Ovarian and breast carcinomas
Myelosupression, alopecia, hypersensitivity
Cisplatin, carboplatin mech:
Cisplatin, carboplatin use:
Testicular, bladder, ovary, lung carcinoma
Cisplatin, carboplatin toxicity:
Nephrotoxicity and acoustic nerve damage. Prevent nephrotoxicity with amifostine (free radial scavenger) and chloride diuresis.
Etoposide, teniposide mech:
eTOPOside inhibits TOPOisomerase II which increases DNA degradation.
Clinical use of etoposide, teniposide:
Solid tumors (particularily testicular and small cell lung cancer), leukemias, lumphomas.
Etopoise, teniposide toxicity:
myelosuppression, GI irritation, alopecia
Irinotecan, topotecan mech:
Inhibit topoisomerase I and prevent DNA unwinding and replication
Irinotecan, topotecan clinical use:
Colon cancer (irinotecan); ovarian and small cell lug cancers (topotecan)
Irinotecan topotecan toxicity:
Severe myelosuppression, diarrhea
Inhibits ribonucleotide reductase which leads to decreased DNA Synthesis (S-phase specific)
Melanoma, CML, sickle cell disease (increased HbF)
Bone marrow suppression, GI upset
Prednisone, prednisolone mech:
may trigger apoptosis. may even work on nondividing cells.
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).
Prednisone, prednisolone toxicity:
Cushing-like symptoms; weight gain, central obesity, muscle breakdown ,cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycmia, psychosis
Tamoxifen, raloxifene mech
SERMS - receptor antagonists in breast and agonists in bone. Block the binding of estrogen to ER + cells
Tamoxifen, raloxifene clinical use
breast cancer treatment (tamoxifen only) and prevention. Raloxifene for osteoporosis.
partial agonist in endometrium, which increases the risk of endometrial cancer; 'hot flashes'
no increase in endometrial carcinoma because it is an endometrial antagonist
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
Trastuzumab (herceptin) clinical use:
HER-2 + breast cancer and gastric cancer (tras2zumab)
Cardiotoxicity. "HEARTceptin' damages the heart
Imatinib (Gleevac) mech:
Tyrosine Kinase inhibitor of bcr-abl (Philadelphia chromosome fusion gene in CML) and c-Kit (common in GI stromal tumors)
CML, GI stromal tumors
monoclonal antibody against CD20, which is found on most B-cell neoplasms
non-hodgkin lymphoma, rheumatoid arthritis (with MTX); ITP
increased risk of progressive multifocal leukoencephalopathy
Small molecule inhibitor to forms of the B-Raf kinase with the V600E mutation
monoclonal antibody against VEGF, inhibits angiogenesis
Bevacizumab clinical use:
Solid tumors (colorectal cancer, renal cell carcinoma)