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63 Cards in this Set
- Front
- Back
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What is methotrexate?
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S-phase specific antimetabolite
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What is mechanism of methotrexate?
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Inhibits dihydrofolate reductase, causing decreased dTMP and therefore decreased DNA adn protein synthesis.
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What can methotrexate be used for?
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RA
Psoriasis Leukemias Lymphomas Abortion |
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What is the toxicity of methotrexate?
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myelosuppression, stomatitis, mucositis, renal dysfunction.
**Myelosuppression is reversible with leucovorin (folinic acid) rescue. Can cause MACROVESICULAR FATTY CHANGE IN THE LIVER!! |
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What is 5-fluorouracil?
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S-phase specific metabolite.
Inhibits thymidylate synthase, causing decrease in dTMP. And decreasing DNA synthesis. |
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What is 5-FU used for?
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Mainly for GI malignancies: colon cancer, gastric, rectal. It has synergism with MTX
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What is the toxicity of 5-FU?
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Myelosuppression; NOT reversible with leucovorin
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What is mechanism of 5-FU?
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Inhiits thymidylate synthase, so cant produce dTMP!
dUMP ------------> dTMP |
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How is methotrexate synergistic with 5 FU?
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MTX inhibits dihydrofolate reductase, which is needed to make THF and then CH2-THF, and this CH2-THF is required to convert dUMP to dTMP.
So what is required to make dTMP? 1) CH-THF (from dihydrofolate reductase) 2) Thymidylate synthase. |
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What is 6-mercaptopurine (6-MP)?
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Agent metabolized into false purine analogs (hence the name)!
Blocks de novo purine synthesis. ***MUST BE ACTIVATED BY HGPRTase!!! |
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What is the toxicity of 6-MP?
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Neutropneia!! Mercaptopurine CAPTUres neutrophils.
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How is 6-MP metabolized?
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By Xanthine oxidase, so if you have allopurinol drug, it will increase the concentration of 6-MP and increase toxicity!
S phase specific metabolite. |
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What is cytarabine (ara-C)
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Used for AML
Blcoks DNA polymerase!! Leukopenia, thrombocytopenia, megaloblastic anemia |
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What is mechanism of cyclophosphamide?
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Alkylating Agent: covalent x-links DNA at guanine N-7!!
Doesnt differentiate between resting and cycling cells. |
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What is one requirement for cyclophosphamide to work?
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Needs bioactivation by the liver! (cytochrome P450).
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What is cyclophosphamide used for?
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Immunosuppression, breast, ovary carcinomas.
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What are side effects of cyclophosphamide?
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Hemorrhagic cystitis (can be prevented by mensa): antidote that helps excrete the toxic metabolit.
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What are nitrosureas used for?
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1) Alkylate DNA. Require liver
2) CROSS BBB --> CNS 3) used for brain tumors. PUlmonary fibrosis if chronic use. |
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What is cisplatin, carboplatin mechanism of action?
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Act like alkylating agents: forms cross links in DNA
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What is cisplatin/carboplatin used for?
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Testicular, bladder, ovary, and lung carcinomas.
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What is toxicity of cisplatin?
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Nephrotoxicity (Cant PISS)
Acoustic nerve damage (MISS what people say). Neuropathy |
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What is busulfan mechanism of action?
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Alkylates DNA
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What are some side effects of busulfan?
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Pulmoanry fibrosis, hyperpigmentation!
Used in CML! |
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What is the mechanism of action of doxorubicin (adriamycin)?
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Generate free radicals and noncovalently intercalates in DNA.
**Part of ABVD combo for Hodgkins and myeloma |
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What is side effects of doxorubicin and daunorubucin?
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cardiotoxicity: delayed cardiomyopathy!
Used as the ABVD combination regimen for Hodgkins, myeloma, sarcoma, and solid tumors. |
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What is the ABVD regimen?
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Adriamycin (doxorubucin)
Bleomycin Vinblastine Dacarbarzine. |
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What is mechanism of action of dACTinomycin?
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Intercalates in DNA
ACTinomycin is used for childhood tumors (children ACT out)!! 1) Wilms Tumor 2) Ewings Sarcoma 3) Rhabdo |
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What is mechanism of bleomycin?
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Free radical formation causing breaks in DNA strand. Works in G2 mainly!!
Forms a ferrous iron oxygen drug complex. |
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What is the side effect of bleomycin?
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Pulmonary fibrosis, skin changes
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What is action of mitomycin C?
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Cross-links DNA
Used for bladder cancer |
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What are side effects of mitomycin C?
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Interstitial pneumonitis, nephrotoxicty.
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What is leukovorin rescue?
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Treatment with methotrexate includes adding leucovorin (folinic acid)
Its a reduced form of folate not requiring Dihydrofolate reductase (which is blocked by methotrexate). Cool thing about leukovorin --> picked up by regular cells more so than cancer cells!! |
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What is mechanism of etoposide (VP-16)?
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G2 phase specific!!
Inhibits topoisomerase II, which increases DNA degradation |
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What stage does bleomycin work on?
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G2
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What stage does etoposide work on?
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Maily on G2 to inhibit topo II
But then indirectly on S inhibiting DNA synthesis. Tangles the cells DNA and it cant divide. |
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What is most common glucocorticoid used in cancer chemotherapy?
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Prednisone. Thought to trigger apoptosis?
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What is toxicity of prednisone?
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Cushing-like symptoms; immunosuppression,
CATARACTS OSTEOPOROSIS HTN Acne |
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What is action of tamoxifen?
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It antagonizes estrogen receptors in the breast, but actually stimulates estrogen receptors of the uterus.
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What is side effect of tamoxifen?
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Can cause endometrial carcinoma via partial agonist effects.
Actually induces a low estrogen state, so causes hot flashes, nausea, vomiting. |
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What is tamoxifen used for?
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Breast Cancer
Osteoporosis. |
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What is action of raloxifene?
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Acts as an antagonist in BOTH breast and endometrial tissue! So mainly used for osteoporosis and breast cancer.
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What is mechanism of trastuzumab (herceptin)?
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Monoclonal antibody against HER-2 receptor. (This is a type of erb-B2 gene overamplification).
Helps kill cancers that overexpress HER-2, possibly through antibody-dependent cytotoxicity. |
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What is HER-2?
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Epidermal growth factor receptor: expressed in cells of breast, endometrium, ovary, and lung.
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What is side effect of trastuzumab?
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Herceptin
Cardiotoxicity. |
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What is imantinib?
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Gleevec
Monoclonal antibody against philadelphia chromosome bcr-abl tyrosine kinase!! TYROSINE KINASE. Used in CML. |
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What is the toxicity of imatinib?
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Gleevec
Fluid retention. |
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What is vincristine, vinblastine mechanism of action?
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M-phase specific alkaloids!!
Bind to tubulin and block polymerization of microtubules, so cant form mitotic spindle. |
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What is side effect of vincristine?
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1) M phase specific
2) Inhibits polymerization of microtubules Neurotoxicity (areflexia, peripheral neuritis). |
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what is side effect of vinblastine?
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Blasts Bone marrow!!
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What is paclitaxel and other taxol mechanism of action?
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1) M-phase specific
2) Bind to tubulin and hyperstabilize polymered microbutules!! Note: you can polymerize, but then stabilized so you cant break down mitotic spindle --> PREVENTS ANAPHASE FROM OCCURRING!! |
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What is action of flutamide?
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1) Anti-androgen
2) Used for prostate cancer 3) Inhibits androgen uptake and binding in target tissue |
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What is side effect of flutamide?
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Impotence, hot flashes, gynecomastia.
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What is anastrazole, letrozole mechanism of action?
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Aromatase inhibotrs, decreasing conversion of androgens to estrogen.
Side effects: hot flashes, edema |
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What is action of leuprolide/goserelin?
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GnRH receptor agonists, which suppresses production of LH and FSH, ultimiately suppressing ovaries and testes.
Used for prostate CA/endometriosis. |
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What is mechanism of rituximab?
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Monoclonal antibody directed against CD20 surface antigen expressed on B-lymphocytes.
ADCC death. |
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What is mechanism of azothioprine?
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It gets converted to 6-MP which is a purine metabolite inhibiting purine synthesis.
Inhibits synthesis of DNA and ultimately proteins. |
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What is side effect of azothioprine?
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Bone marrow depression
Used for non-selective immunosuppression for organ transplant. |
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What is mechanism fo action of mycophenolate?
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inhibits inosine monophosphate dehydrogenase. This blcoks formation of GMP. Inhibits purines.
Also used for immunosuppression! |
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What is mechanism of action of cyclosporine?
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inhibits gene transcription of several factors produced by activated T cells including IL-2.
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What is side effect of cyclosporine?
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nephrotoxicity.
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What is mechanism of action of tacrolimus (FK 506)?
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Diffuses into T cells where it binds to FK binding protein causing inhibition of cytokine synthesis.
10-100x more potent that cyclosporine. |
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What is murumonab (OKT-3) MOA?
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OKT-3 is a monoclonal Ab directed against the CD3 molecule of human T cells!!
Used ina cute rejection of renal, cardiac, or hepatic allografts. |
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When is muromonab contrindicated?
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In patients with history of seizure, heart failure, or pregnancy.
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