Term
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Definition
-competitive inhibitor of dihydrofolate reductase (DHFR)
-- uses
a)cancer (choriocarcinoma)
b)mmunosuppressant: RA, psoriasis, IBD, Chron's
c) antibiotic -- pneumocystitis jirovecii (w/AIDS)
d) abortifacient - in first trimester (combined w misoprostrol PGE1) |
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Term
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Definition
| -antibiotic for Pneumocystis jirovecii (assoc. w AIDS) -- given w/ methotrexate |
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Term
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Definition
| antibiotic- best antifolate for treatment of Pneumocystis jiroveci |
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Term
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Definition
| -selective, competitive inhibitor of BACTERIAL dihydrofolate reductase (DHFR), typically combined with SULFAMETHOXAZOLE |
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Term
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Definition
| -- blocks dihydropeteroate synthetase, given with Trimethoprim -- to synergistically block successive steps in folate synthesis path in bacteria |
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Term
| Cisplatin & MECHLORETHAMINE |
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Definition
| -- both anticancer drugs associated with severe nausea-- affects compliance |
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Term
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Definition
| x-linking agent of DNA repair and trapping agent ; form of resistance to cancer drug--- AFFECTS MECHANISM OF ACTION |
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Term
| 5-FLUOROURACIL, CYCLOPHOSPHAMIDE, IRINOTECAN |
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Definition
alterations that affect drug concentrations INSIDE THE TUMOUR CELL;
--decreased activation of prodrugs |
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Term
| alterations that affect drug concentrations INSIDE THE TUMOUR CELL: --decreased accumulation |
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Definition
decreased accumulation:
decreased transport into the cell: folate analogues, MECHLORETHAMINE, platins
increased export from the cell due upregulation of efflux transporters (esp. increased P-glycoprotein): natural products (esp. anthracyclines, vinca alkaloids, taxanes, epipodophyllotoxins)
this is an important cause of multidrug resistance |
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Term
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Definition
-- Calcium channel blocker
-- can reverse increased levels of P-glycoprotein (assoc. w/ MDR d/t mdr-1 gene tx. upregulation) |
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Term
| Methotrexate & Pemetrexed |
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Definition
Mech-inhibit dihydrofolate reductase
Site-Block nucleotide synth (both purines and pyrimidines)
Action- Prevent DNA synthesis |
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Term
| 6-Mercaptopurine & 6-Thioguanine |
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Definition
Mech- "psuedofeedback inhibition" of PNP and PRPP
Site-Block purine synthesis
Action- Prevent DNA synthesis |
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Term
| Capecitabine & 5-Flurouracil & Pemetrexed |
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Definition
Mech-inhibit thymidylate synthase
Site-block pyrimidine synthesis
Action-Prevent DNA synthesis |
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Term
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Definition
Mech- Inhibit ribonucleotide reductase
Site- Block generation of deoxyribonucleotides
Action- Prevent DNA synthesis |
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Term
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Definition
Mech- inhibit DNA polymerase
Site- Block DNA synthesis
Action- prevent DNA synthesis |
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Term
| Busulfan, Carmustine (BCNU), Cyclophosphamide, Dacarbazine, Ifosfamide, Lomustine (CCNU), Mechlorethamine, Melphalan |
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Definition
Mech-Alkylating agents
Site- Crosslink DNA
Action- Disrupt DNA, prevent DNA repair and/or interfere with RNA synthesis |
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Term
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Definition
Mech- Miscellaneous
Site- Crosslink DNA
Action-- Disrupt DNA, prevent DNA repair and/or interfere with RNA synthesis |
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Term
| Daunorubicin & Doxorubicin |
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Definition
Mechanism- Anthracycline antibiotics
Site- Intercalate or form adducts w/ DNA
Action- Disrupt DNA, prevent DNA repair and/or interfere with RNA synthesis |
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Term
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Definition
Mech- Free radical generation
Site- Cause DNA strand Breaks
Action- Disrupt DNA, prevent DNA repair and/or interfere with RNA synthesis |
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Term
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Definition
Mech- Form topoisomerase II-DNA complexes
Site- Cause DNA strand breaks
Action- Disrupt DNA, prevent DNA repair and/or interfere with RNA synthesis |
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Term
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Definition
Mechanism- Inhibit topoisomerase I
Site- Cause DNA strand breaks
Action- Disrupt DNA, prevent DNA repair and/or interfere with RNA synthesis |
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Term
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Definition
Mech- Generate H2O2?
Site - Cause DNA strand breaks
Action- Disrupt DNA, prevent DNA repair and/or interfere with RNA synthesis |
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Term
| Vincristine & Vinblastine |
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Definition
Mech- Terminate spindle assembly
Site- Disrupt spindle formation
Action- Interrupt mitosis |
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Term
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Definition
Mech- Enhance spindle formation
Site- Disrupt spindle formation
Action-Interrupt mitosis |
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Term
| Dexamethasone & Prednisone |
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Definition
Mech- glucocorticoids
Site- immunosuppressives
Action- Immune system modulators |
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Term
| IL-2, IFN-alpha, TNF-alpha |
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Definition
Mech- cytokines
Site- Immune system stimulants
Action- Immune system modulators |
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Term
| Alemtuzumab, Cetuximab, Denileukin diftitux, Edrecolomab, Gemtuzumab, ibritumomab, Rituximab, Tositumomab, Trastuzumab |
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Definition
Mech- monoclonal Ab's and fusion proteins
Site- Immune system stimulants
Action- Immune system modulators |
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Term
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Definition
Mech- N/A
Site- deplete L-asparagine
Action- interfere with protein synthesis or fx. |
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Term
| Dasatinib, Imatinib, Nilotinib |
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Definition
Mech- Block bcr-abl gene
Site- Signal transduction ( tyrosine kinase) inhibitors
Action- Interfere with protein synthesis or fx. |
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Term
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Definition
Mech- block EGFR
Site - Signal transduction (tyrosine kinase) inhibitors
Action- interfere with protein synthesis or function |
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Term
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Definition
Mech- block Her2 & EGFR
Site- Signal transduction (tyrosine kinase) inhibitors
Action- interfere with protein synthesis or function |
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Term
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Definition
Mech- Block multiple kinases
Site- Signal transduction (tyrosine kinase inhibitors)
Action- interfere with protein synthesis or function |
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Term
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Definition
Mech- N/A
Site- Inhibit 26S proteosome
Action- Interfere with protein synthesis or function |
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Term
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Definition
Mech- N/A
Site- Inhibit HDAC
Action- Interfere with protein synthesis or function |
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Term
| Angiostatin, Bevacizumab, IL-12, IFN-a, Thalidomide |
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Definition
Mech- N/A
Site- N/A
Action- prevent angiogenesis |
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Term
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Definition
Mech- Retinoid
Site- N/A
Action- Induce Differentiation |
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Term
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Definition
Mech- Rexinoid
Site- N/A
Action- Induce Differentiation |
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Term
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Definition
Mech- misc.
Site- N/A
Action- Induce differentiation |
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Term
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Definition
Mech- GnRH agonists
Site- Inhibit LH and FSH secretion
Action- Interfere w/ hormone fx
--a- Decrease steroid conc.
--b- Antagonize receptors |
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Term
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Definition
Mech- GnRH antagonist
Site- Inhibit LH and FSH secretion
Action-Action- Interfere w/ hormone fx
--a- Decrease steroid conc.
--b- Antagonize receptors |
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Term
| Aminoglutethimide, Anastrazole, Letrozole |
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Definition
Mech-Reversible inhbitors
Site- Inhibit aromatase (prevent estrogen synthesis)
Action- Action- Interfere w/ hormone fx
--a- Decrease steroid conc.
--b- Antagonize receptors |
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Term
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Definition
Mech- Irreversible inhibitor
Site- Inhibit aromatase (prevent estrogen synthesis)
Action- Interfere w/ hormone fx
--a- Decrease steroid conc.
--b- Antagonize receptors |
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Term
| Dutasteride & Finasteride |
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Definition
Mech- N/A
Site- Inhbit 5alpha reductase (prevent androgen synthesis)
Action- Action- Interfere w/ hormone fx
--a- Decrease steroid conc.
--b- Antagonize receptors |
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Term
| Bicalutamide, Flutamide, Nilutamide |
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Definition
Mech- N/A
Site-Anti-androgens
Action- Interfere w/ hormone fx
--a- Decrease steroid conc.
--b- Antagonize receptors |
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Term
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Definition
Mech- SERMS
Site- anti-estrogens
Action- Interfere w/ hormone fx
--a- Decrease steroid conc.
--b- Antagonize receptors |
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Term
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Definition
Mech- SERD
Site- Anti-estrogens
Action- Interfere w/ hormone fx
--a- Decrease steroid conc.
--b- Antagonize receptors |
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Term
Protein Fx:
Antineoplastic:Aminoglutethamide, Anastrazole, Exemestane, Letrozole |
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Definition
Normal Action- Convert androstenedione to estrone
Protein- Aromatase |
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Term
Protein Fx:
Antineoplastic:L-Asparaginase |
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Definition
Normal Action- hydrolysis of asparagine to aspartic acid and ammonia
Protein- L-asparaginase |
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Term
Protein Fx:
Antineoplastic:Dasatanib, Imatinib, Nilotinib |
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Definition
Normal Action- Activation of transcription factors via cascade pathway
Protein- BCR-ABL ( non-receptor tyrosine kinase) |
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Term
Protein Fx:
Antineoplastic:Ibritumomab, Rituximab, Tositumomab |
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Definition
Normal Action-Transmembrane protein found on pre-B and mature B lymphocytes
Protein- CD-20 ( B-lymphocyte restricted differentiation antigen Bp35) |
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Term
Protein Fx:
Antineoplastic:Ibritumomab, Rituximab, Tositumomab |
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Definition
Normal Action-Transmembrane protein found on pre-B and mature B lymphocytes
Protein- CD-20 ( B-lymphocyte restricted differentiation antigen Bp35) |
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Term
Protein Fx:
Antineoplastic: gemtuzumab |
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Definition
Normal Action- Sialic acid- dependent cytoadhesion molecule expressed by monocytic/myeloid lineage cells
Protein: CD33 (gp67, p67) |
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Term
Protein Fx:
Antineoplastic:Alemtuzumab |
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Definition
Normal Action- CAMPATH-1 AG; GPI-anchored protein expressed at high levels on thymocytes, lymphocytes, monocytes, and macrophages
Protein- CD52 |
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Term
Protein Fx:
Antineoplastic: Cyclophosphamide, procarbazine, Daunorubicin, Doxorubicin, Paclitaxel |
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Definition
Normal Action- hydroxylation of aromatic and aliphatic commpounds ( can activate or inactivate antineoplastic drugs)
Protein- Cytochrome P450 |
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Term
Protein Fx:
Antineoplastic: 5-Fluorouracil |
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Definition
Normal Action- Liver and gut enzyme that degrade thymidine nucletides
Protein- Dihydropyrimidine dehydrogenase |
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Term
Protein Fx:
Antineoplastic:Methotrexate Pemetrexed |
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Definition
Normal Action- Converts dihydrofolate to tetrahydrofolate
Protein- Dihydrofolate reductase (DHFR) |
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Term
Protein Fx:
Antineoplastic: Cytarabine, Gemcitabine |
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Definition
Normal Action- Copies DNA templates during DNA replication
Protein- DNA polymerase |
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Term
Protein Fx:
Antineoplastic: Cetuximab, Erlotinib, Gefitinib, Lapatanib |
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Definition
Normal Action- binds epidermal GF
Protein- EGFR |
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Term
Protein Fx:
Antineoplastic: Interferon Alpha |
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Definition
Normal action: Angiogenic protein
Protein: fibroblast growth factor (FGF) |
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Term
Protein Fx:
Antineoplastic: Daunorubicin, Doxorubicin |
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Definition
Normal Action: oxidizes glutathione
Protein- glutathione peroxidase |
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Term
Protein Fx:
Antineoplastic: MDR |
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Definition
Normal Action: drug transport out of cells
Protein- P-glycoprotein |
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Term
Protein Fx:
Antineoplastic: 6-Mercaptopurine, 6-Thioguanine |
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Definition
Normal Action: Converts GMP to GDP
Protein: Guanylyl kinase |
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Term
Protein Fx:
Antineoplastic: Lapatinib, Trastuzumab |
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Definition
Normal Action- Transmembrane protein overexpressed in breast cancer
Protein: HER2 |
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Term
Protein Fx:
Antineoplastic: Vorinostat |
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Definition
Normal Action: Removes acetyl groups from lysine residues leading to the formation of condensed and transcriptionally silenced chromatin
Protein: Histone deacetylase (HDAC) |
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Term
Protein Fx:
Antineoplastic: 6-Mercaptopurine, 6-Thioguanine |
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Definition
Normal Action: "Salvage" enzyme for reconversion of purines
Protein: Hypoxanthine-guanine phophoribosyl transferase (HGPRT) |
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Term
Protein Fx:
Antineoplastic: Denileukin Diftitux |
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Definition
Normal Action: Cytokine that induces and expands a T-cell response
Protein: IL-2 (itself is an antineoplastic) |
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Term
Protein Fx:
Antineoplastic:Alkylating Agents |
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Definition
Normal Action: Cell cycle checkpoint that is mutated in 50% of human cancers
Protein: p53 gene product |
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Term
Protein Fx:
Antineoplastic: Alkylating agents |
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Definition
Normal Action: cell cycle checkpoint that is mutated in 50% of human cancers
Protein: p53 gene product |
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Term
Protein Fx:
Antineoplastic: Arsenic Trioxide Tretinoin |
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Definition
Normal Action: Fusion protein of retinoic acid receptor and promyelocytic protin produced via translocation in APL
Protein: PML-RAR alpha |
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Term
Protein Fx:
Antineoplastic: Bortezomib |
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Definition
Normal Action: Large protein complex that degrades ubiquitinated proteins
Protein: 26S proteosome |
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Term
Protein Fx:
Antineoplastic: 6-Mercaptopurine, 6-Thioguanine |
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Definition
Normal Action- 1st committed step in purine synthesis
Protein: PRPP glutamyl amidotransferase |
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Term
Protein Fx:
Antineoplastic: 5-Fluorouracil |
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Definition
Normal Action: Converts UMP to UDP
Protein: Pyrimidine monophosphate kinase |
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Term
Protein Fx:
Antineoplastic: Gemcitibane Hydroxyurea |
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Definition
Normal Action: Reduces nucleoside diphosphates to deoxy forms
Protein: Ribonucleotide reductase |
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Term
Protein Fx:
Antineoplastic: Capecitabine |
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Definition
Normal Action: Converts capecitabine to 5-FU (preferentially in cancer cells)
Protein: Thymidine phosphorylase |
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Term
Protein Fx:
Antineoplastic: Irinotecan |
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Definition
Normal Action: Reversible nuclease that breaks phophodiesterase bonds resulting in a transient single-strand break
Protein: Topoisomerase I |
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Term
Protein Fx:
Antineoplastic: Daunorubicin, Doxorubicin, Etoposide |
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Definition
Normal Action: Makes a temporary DNA break, then causes 2nd half of double helix to pass through the break before resealing it.
Protein: Topoisomerase II |
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Term
Protein Fx:
Antineoplastic: Capecitabine, 5-Fluorouracil, Pemetrexed |
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Definition
Normal Action: TMP synthesis
Protein: Thymidylate synthase |
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Term
Protein Fx:
Antineoplastic:Ixabepilone, Paclitaxel, Vinblastine, Vincristine |
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Definition
Normal Action: key component of mitotic spindle and microtubules (axon transport, cytoskeleton)
Protein: Tubulin |
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Term
Protein Fx:
Antineoplastic: Allopurinol, 6-Mercaptopurine |
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Definition
Normal Action: converts xanthine to uric acid
Protein: Xanthine oxidase |
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Term
Protein Fx:
Antineoplastic: Bevaciximab |
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Definition
Normal Action: Angiogenic Growth Factor
Protein: VEGF |
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Term
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Definition
| Carmustine, Cisplatin, Cyclophosphamide, Lomustine, Methotrexate, Vincristine |
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Term
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Definition
| Asparaginase, Busulfan, Carmustine, Cyclophosphamide, Daunorubicin, 6-Mercaptopurine, Methotrexate, 6-Thioguanine |
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Term
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Definition
| Asparaginase, Carmustine, Cisplatin, Cytarabine, Etoposide, 5-Fluorouracil, Methotrexate, Procarbazine, Vinblastine, Vincristine |
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Term
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Definition
| Doxorubicin, Daunorubicin, Trastuzumab |
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Term
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Definition
| Amsacrine, Bleomycin, Cisplatin, Nitrogen mustards, 5-fluorouracil, methotrexate, Paclitaxel |
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Term
Emitic Potential of Antineoplastics:
High (>90%) |
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Definition
| Cisplatin, Mechlorethamine |
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Term
Emitic Potential of Antineoplastics:
Moderately High (60-90%) |
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Definition
| Carmustine, Cyclophosphamide, Dactinomycin, Lomustine |
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Term
Emitic Potential of Antineoplastics:
Moderate (30-60%) |
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Definition
| Asparaginase, Daunorubicin, Doxorubicin, Fluorouracil |
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Term
Emitic Potential of Antineoplastics:
Moderately low (10-30%) |
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Definition
| Bleomycin, Etoposide, hydroxyurea, Melphalan, 6-Mercaptopurine, Methotrexate, Vinblastine |
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Term
Emitic Potential of Antineoplastics:
Low (<10%) |
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Definition
| Androgens, Busulfan, Estrogens, Progestins |
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