Pharm 49: Anticancer Drugs
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71 terms
Terms | Definitions |
|---|---|
 5-Fluorouracil | MOA: converted to a deoxyribonucleotide which inhibits thymidylate synthase - DNA synthesis is inhibited due to thymidine (pyrimidine) deficiency -> it is also incoporated into RNA USE: Systemically for adenocarcinomas, topically for skin cancer -> Leucovorin increases effects by allowing more metabilite to incorporate into RNA AE: myelosuppression, mucositis, hand-foot syndrome (skin exfoliation on palm and feet), alopecia |
| 6-Mercaptopurine | MOA: converted to TIMP -> inhibits de novo purine synthesis and blocks formation of AMP and GMP -> metabolised to thiouric acid by xanthine oxidase USE: ALL AE: bone marrow suppression, hepatotoxicity, nausea/vomiting Must reduce dosage if coadministered with allopurinol (xanthine oxidase inhibitor) |
| 6-Thioguanine | MOA: purine antagonist -> inhibits DNA & RNA synthesis by decreasing intracellular GMP concentrations USE: AML AE: bone marrow suppression, hepatotoxicity, nausea/vomiting |
| Capecitabine | MOA: Oral prodrug of 5-FU converted to 5-FU by thymidine phosphorylase inside tumor cells USE: orally for metastatic breast cancer and colorectal cancer AE: similar to 5-FU |
| Cytarabine | MOA: S phase specific anti-metabolite -> transformed to active form and competitively inhibits DNA polymerase USE: AML for induction and CML in blast crisis AE: Myelosuppression (common) and ataxia |
| Gemcitabine | MOA: pyrimidine analog competes with cytidine -> inhibits chain elongation USE: Pancreatic cancer, NSC lung cancer, ovarian cancer, etc AE: Myelosuppression, alopecia, flu-like symptoms, elevation of liver enzymes |
| Methotrexate | MOA: inhibits dihydrofolate reductase which converts dihydrofolic acid into tetrahydrofolic acid USE: Choriocarcinoma, ALL, Burkitt's, Osteosarcoma, breast cancer AE: bonemarrow suppression (give Leucovorin - tetrahydrofolic/folinic acid to supply reduced folate which overcomes blockade), renal damage (due to crystal deposition in kidney tubules -> hydrate pt to prevent), pulmonary toxicity (especially in children), hepatic fibrosis (over long period) |
| Bleomycin | MOA: anti-tumor antibiotic -> acts at G2 by inducing free radical mediated DNA strand breaks, reduced iron mediates reduction of molecular oxygen to free radicals PK: inactivated by cellular metabolism (hydrolase -> seen in tissues that have low amounts of this enzyme), eliminated exclusively by kidney USE: Hodgkin's lymphoma, testicular cancer, Kaposi Sarcoma AE: pneumonitis followed by pulmonary fibrosis, skin reaction, Raynaud's, Retroperitoneal fibrosis *little effect on bone marrow (bone marrow sparing) |
| Dactinomycin | MOA: anti-tumor antibiotic -> cell cycle nonspecific (G0) -> binds DNA non-covalently USE: Wilm's tumor and Sarcomas AE: Highly vesicant (extravasation can lead to necrosis to the tissue), Erythema at sites of prior radiation (radiation recall reaction) |
| Daunorubicin, Doxorubicin | MOA: anthracycline antibiotic -> inhibition of topoisomerase II (DNA breaks) -> formation of ROS damage DNA, cell membrane, proteins -> alters membrane fluiditiy and ion transport USE: broad anti-tumor activity -> breast cancer, AML, lymphomas, sarcomas AE: Dilated cardiomyopathy (prevent with dexrazoxane), myelosuppression, nausea/vomiiting, alopecia, mucositis, erythema at sites of prior radiation (radiation recall reaction), highly vesicant |
| Etoposide & Teniposide | MOA: epipodophyllotoxins -> acts at late S and early G2 -> inhibits topoisomerase II, prevents re-ligation of DNA strand breaks USE: Germ cell tumor, AML, lung cancer AE: bonemarrow suppression (give Filgrastim/GM-CSF), *definitive link between use of first drug and leukemia |
| Vinblastine | MOA: binds b-tubulin and prevents formation of microtubules -> cells arrested in metaphase USE: Testicular cancers AE: bonemarrow suppression (give Filgrastim/GM-CSF) |
| Vincristine | MOA: binds b-tubulin and prevents formation of microtubules -> cells arrested in metaphase USE: Hodgkin's lymphoma AE: peripheral neuropathy (myelosuppression is minimal - bone sparing drug) |
| Vinorelbine | MOA: binds b-tubulin and prevents formation of microtubules -> cells arrested in metaphase USE: Non small cell lung cancer AE: granulocytopenia |
| Docetaxel | MOA: enhances tubulin polymerization and stabilizes microtubules in polymerized state (irreversibly binds) -> cells arrested in metaphase USE: ovarian and breast cancer AE: Skin toxicity and fluid retention leading to pleural and peritoneal effusions |
| Paclitaxel | MOA: enhances tubulin polymerization and stabilizes microtubules in polymerized state (irreversibly binds) -> cells arrested in metaphase USE: ovarian and breast cancer AE: Severe allergic reaction (attributed to cremophor vehicle), neutropenia and alopecia is universal |
| Irinotecan | MOA: Camptothecin -> topoisomerase I inhibition USE: Colon and rectal cancer AE: Severe diarrhea, myelosuppresion |
| Topotecan | MOA: Camptothecin -> topoisomerase I inhibition USE: Metastatic ovarian cancer (Cisplatin resistant) AE: Neutropenia, thrombocytopenia, anemia |
| Chlorambucil | MOA: Nitrogen mustard alkylating agent -> alkylation at N7 position of guanine in DNA -> miscoding by abnormal base pairing or excision (strand breakage), cross-linking of DNA and ring cleavage may also occur USE: CLL AE: hematologic toxicities |
| Cyclophosphamide | MOA: Nitrogen mustard alkylating agent -> alkylation at N7 position of guanine in DNA -> miscoding by abnormal base pairing or excision (strand breakage), cross-linking of DNA and ring cleavage may also occur PK: oral, activated by hepatic enzymes, metabolizes to toxic compound acrolein (Mesna inactivates, need to maintain high urine output) USE: widely used for cancers of adrenal cortex, bladder, bone, cervix, endometrium, lung, non-Hodgkins lymphoma, etc. AE: Hemorrhagic cystitis (prevent with MESNA), immunosuppression, bone marrow suppresion, nausea/vomiting, alopecia, gonadal failure (amenorrhea/sterility), SIADH |
| Ifosfamide | MOA: Nitrogen mustard alkylating agent -> alkylation at N7 position of guanine in DNA -> miscoding by abnormal base pairing or excision (strand breakage), cross-linking of DNA and ring cleavage may also occur USE: more potent than cyclophosphamide, 3rd line for testicular CA AE: Hemorrhagic cystitis (prevent with MESNA), neurotoxicity, thrombopenia |
| Mechlorethamine | MOA: Nitrogen mustard alkylating agent -> alkylation at N7 position of guanine in DNA -> miscoding by abnormal base pairing or excision (strand breakage), cross-linking of DNA and ring cleavage may also occur USE: highly vesicant, used in NHL AE: bone marrow depression, extravasation (blistering) |
| Melphalan | MOA: Nitrogen mustard alkylating agent -> alkylation at N7 position of guanine in DNA -> miscoding by abnormal base pairing or excision (strand breakage), cross-linking of DNA and ring cleavage may also occur USE: multiple myeloma AE: hematologic toxicities |
| Busulfan | MOA: Alkyl Sulfonate alkylating agent -> alkylation at N7 position of guanine in DNA -> miscoding by abnormal base pairing or excision (strand breakage), cross-linking of DNA and ring cleavage may also occur USE: CML AE: adrenal insufficiency, pulmonary fibrosis, skin pigmentation |
| Carmustine, Lomustine, Semustine | MOA: Nitrosurea alkylating agents -> alkylates nucleic acids and proteins, producing single-strand breaks and inter-strand cross-linkage of DNA (crosses BBB) USE: high lipophilicity (facilitates CNS entry) -> brain tumors AE: GI distress, delayed myelosuppression, CNS dysfunction |
| Dacarbazine | MOA: Triazine alkylating agent -> alkylation at N7 position of guanine in DNA -> miscoding by abnormal base pairing or excision (strand breakage), cross-linking of DNA and ring cleavage may also occur PK: synthetic drug requires activation by liver microsomal system USE: Hodgkins disease, soft tissue sarcoma, melanoma AE: Myelosuppression, nausea and vomiting |
| Procarbazine | MOA: Methylhydrazine alkylating agent -> alkylation at N7 position of guanine in DNA -> miscoding by abnormal base pairing or excision (strand breakage), cross-linking of DNA and ring cleavage may also occur USE: Hodgkin's disease (combo therapy) AE: Nausea, vomiting, myelosuppression, hemolytic anemia, pulmonary effects, peripheral sensory neuropathy, disulfiram like reaction (avoid alcohol) *Teratogenic, mutagenic, leukemogenic |
| Cisplatin | MOA: platinum compound alkylating agent -> alkylation at N7 position of guanine in DNA -> miscoding by abnormal base pairing or excision (strand breakage), cross-linking of DNA and ring cleavage may also occur USE: wide range of tumors -> germ cell tumors, ovarian cancer, NSC lung cancer *solid tumors, bladder CA, ovarian CA AE: Nephrotoxicity (good hydration, mannitol, amifostine - prevents free radical damage), severe nausea and vomiting (stimulation of CTZ), neurotoxicity (peripheral neuropathy and deafness) |
| Carboplatin | MOA: platinum compound alkylating agent -> alkylation at N7 position of guanine in DNA -> miscoding by abnormal base pairing or excision (strand breakage), cross-linking of DNA and ring cleavage may also occur USE: wide range of tumors -> germ cell tumors, ovarian cancer, NSC lung cancer *used when pt can't be hydrated (alternative to cisplatin) AE: milder than cisplatin -> severe nausea and vomiting (stimulation of CTZ), nephrotoxicity (electrolyte imbalance), neurotoxicity (peripheral neuropathy and deafness) *myelosuppression |
| Oxaliplatin | MOA: platinum compound alkylating agent -> alkylation at N7 position of guanine in DNA -> miscoding by abnormal base pairing or excision (strand breakage), cross-linking of DNA and ring cleavage may also occur USE: wide range of tumors -> germ cell tumors, ovarian cancer, NSC lung cancer *Advanced colon cancer AE: milder than cisplatin -> severe nausea and vomiting (stimulation of CTZ), nephrotoxicity (electrolyte imbalance), neurotoxicity (peripheral neuropathy and deafness) *myelosuppression |
| Dexamethasone, Hydrocortisone, Prednisone, Prednisolone | MOA: Bind intra-cytoplasmic receptor which then binds to nuclear receptor modulating protein expression USE: ALL, Hodgkin's Lymphoma, NHL, multiple myeloma, palliative care (improve feeling of well being), spinal cord compression due to metastasis (relieve edema), manage autoimmune anemia and thrombocytopenia AE: immunosuppression leading to infections, mood swings, osteoporosis, hyperglycemia, poor wound healing |
| Diethylstilbestrol, Ethinylestradiol | MOA: binds cytoplasmic receptor which then moves to nucleus to modulate protein expression USE: Prostate CA, AE: risk of thromboembolism, migraine, cholestasis and mood changes, gynecomastia and impotence in men *Contraindicated in pts with breast and endometrial cancer |
| Tamoxifen | MOA: selective estrogen receptor modulator -> agonistic in endometrium and bone, antagonist in breast tissue USE: primary therapy for metastatic breast cancer in men and postmenopausal women, patients with estrogen-receptor+ tumors more likely to respond -> prophylactic for women with high risk of breast cancer AE: hot flushes and thrombosis, fluid retention, risk of endometrial cancer if used for long period |
| Aminoglutethemide | MOA: steroidal reversible inhibitor of aromatase -> prevents peripheral conversion of androstenedione to estriol in adipose tissue -> also inhibits conversion of cholesterol to pregnenolone -> inhibits extra-adrenal synthesis of estrone and estradiol USE: ER+ metastatic breast cancer AE: Adrenal insufficiency, dizziness, lethargy, visual blurring, rash |
| Anastrozole, Letrozole | MOA: non-steroidal reversible inhibitor of aromatase -> prevents peripheral conversion of androstenedione to estriol in adipose tissue USE: treatment of advanced ER+ breast cancer that is resistant to tamoxifen AE: hot flushes and headache |
| Exemestane, Formestane | MOA: steroidal irreversible inhibitor of aromatase -> prevents peripheral conversion of androstenedione to estriol in adipose tissue USE: Advanced estrogen receptor positive cancer AE: mood changes, acne, hair growth |
| Hydroxyprogesterone, Megestrol | MOA: Progestins USE: endometrial cancer, in palliative care to improve appetite AE: weight gain, depression, edema, acne, decreased HDL |
| Fluoxymesterone, Testosterone | MOA: Androgens USE: palliative care to improve feeling of well being and appetite |
| Goserelin, Leuprolide | MOA: Antiandrogens -> continuous dose (not pulsatile) causes reversible medical castration -> decreased LH and FSH USE: prostate cancer, sometimes fibroid uterus AE: initial flare-up of androgen dependent cancer may occur, decreased bone mass, hot flushes, impotence |
| Flutamide | MOA: androgen receptor blocker USE: Prostate cancer AE: Gynecomastia & GI distress *given with GnRH to prevent initial tumor flare up |
| Hydroxyurea | MOA: inhibits ribonucleotide reductase -> depletion of dNTP pools -> inhibits DNA synthesis -> S phase specific USE: melanoma, CML, sickle cell disease to increase HbF AE: leukopenia (reversible upon discontinuation), mild GI toxicity, mild dermatologic changes with prolonged therapy |
| L-Asparaginase | MOA: causes catabolic depletion of serum asparagine to aspartic acid and ammonia -> reduced glutamine levels, inhibition of protein synthesis USE: Childhood acute leukemias (AML, ALL) AE: Pancreatitis and bleeding*, hypersensitivity (anaphylaxis), hyperglycemia, headache |
| Arsenic Trioxide | MOA: causes differentiation of leukemic cells USE: acute pro-myelocytic leukemia (M3 - AML -> RARA+) AE: headache, cardiac dysrhythmias, fluid retention, increases risk of skin cancers *Avoid in pregnancy (duh) |
| Interferon 2α | MOA: Stimulates NK cells, increases expression of HLA molecules on tumor cells USE: CML, Hairy cell leukemia, Kaposi Sarcoma AE: fever, myalgia, headache, loss of appetite, depression |
| Interferon 2β | MOA: Stimulates NK cells, increases expression of HLA molecules on tumor cells USE: Melanoma, follicular lymphoma, AIDS related Kaposi Sarcoma AE: fever, myalgia, headache, loss of appetite, depression |
| Imatinib | MOA: signal transduction inhibitor -> inhibits tumor TK activity USE: BCR-ABL+ CML/ALL/GIST AE: fluid retention, edema, hepatotoxicity, thrombocytopenia |
| Gefitinib | MOA: Signal transduction inhibitor -> inhibits epidermal growth factor receptor activity USE: NSC lung cancer AE: acne like skin lesions, nausea, diarrhea |
| Bortezomib | MOA: Signal transduction inhibitor -> Inhibits proteosome which has chymotrypsin like activity USE: multiple myeloma and mantle cell lymphoma AE: thrombocytopenia and neuropathy |
| Cetuximab | MOA: Signal transduction inhibitor -> inhibits EFGR signaling USE: colorectal cancer, head and neck cancer AE: infusion reaction, skin rash, fatigue |
| Erlotinib, Lapatinib | MOA: Signal transduction inhibitor -> EGFR tyrosine kinase inhibitor USE: NSC lung cancer, pancreatic cancer AE: skin rash & interstitial lung disease |
| Sorafenib | MOA: Signal transduction inhibitor -> multiple receptor kinase inhibition -> VEGF-2 & 3, PDGFR USE: Renal cell cancer and hepatocellular carcinoma AE: Skin rash and fatigue |
| Sunitinib | MOA: Signal transduction inhibitor -> multiple receptor kinase inhibition -> VEGF-1, 2 & 3, PDGFR USE: Renal cell cancer and GIST AE: Skin rash and bleeding |
| Trastuzumab | MOA: Signal transduction inhibitor -> Epidermal growth factor receptor protein 2 USE: Breast cancer AE: Congestive heart failure & infusion related side effects |
| Leucovorin | MOA: tetrahydrofolic/folinic acid -> supply reduced folate which overcomes blockade by certain drugs USE: prevents bone marrow suppression with methotrexate, increases efficacy of 5-FU |
| Dexrazoxane | MOA: iron chelating agent -> reduces free radical damage USE: decreases cardiotoxicity with anthracyclines Doxorubin and Daunorubicin |
| Filgrastim | MOA: GM-CSF USE: prevents neutropenia with most chemo drugs (etoposide) |
| Mesna | MOA: inactivates toxic compound acrolein -> need to maintain high urine output USE: prevent hemorrhagic cystitis with cyclophosphamide and ifosfamide |
| Amifostine | MOA: prevents free radical damage USE: decreases renal toxicity with cisplatin |
| Anticancer drugs | kill cancer at a constant fraction -> want a 5-log kill |
| Rapidly dividing normal cells | bonemarrow (neutropenia and thrombocytopenia), GI mucosa (mucositis and blisters), hair follicles (alopecia), gonads (infertility) |
| Hodgkin's lymphoma regimen | ABVD -> Adriamycin (doxorubicin -> S phase), Bleomycin (G2 phase), Vincristine (M phase), Dacarbazine (cell cycle nonspecific -> G0) |
| ABVD toxicity | cardiotoxicity, pulmonary fibrosis, neurotoxicity, bone marrow toxicity |
| Testicular cancer | BEP -> Bleomycin (G2), Etoposide (Late S/early G2), Platinum (Cisplatin -> nonspecific/G0) |
| BEP toxicity | pulmonary fibrosis, bone marrow toxicity, ototoxicity/nephrotoxicity |
| Adjuvant chemo | chemo in addition to surgery/radiotherapy |
| Neo-adjuvant chemo | chemo given before surgery to decrease size of tumor |
| Induction chemo | chemo given to obtain complete remission from the tumor (usually blood cancers) |
| Mitotic inhibitors | Vincristine, Vinblastine, Paclitaxel & Docetaxel |
| DNA synthesis inhibitors | Methotrexate, Cytarabine, 6-mercaptopurine (all anti-metabolites) |
| Cell cycle non-specific drugs (have effects on G0) | all alkylating drugs and most DNA intercalating drugs |
| G2 phase inhibitors | Bleomycin, etoposide and teniposide |
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