Antineoplastic Agents Flashcards
Cyclophosphamide
Less reactive derivative of mechlorethamine
DNA alkylating activity requires activation in liver or tumor
Oral administration
Mechlorethamine
Nitrogen mustard
Alkylating agent
Highly reactive DNA alkylating/damaging agent
Causes necrosis at the site of injection
Nitrosoureas
Alkylating agent
Crosses BBB
Used against brain tumors
Procarbazine
Alkylating agent Carcinogenic Metabolized to alkylating and free radical intermediates Used for Hodgkin's disease Leukemogenic
Cisplatin
Platinum coordination complex
Inhibits DNA biosynthesis
Tx: ovarian and testicular cancer
SE: nephrotoxicity, acoustic nerve dysfunction
Methotrexate
Anti-tumor antimetabolite Folic acid analog Dihydrofolate Reductase inhibitor Blocks synthesis of DNA, RNA, and protein precursors S phase-specific
Leucovorin(folinic acid)
Rescue drug for chemo
Used as antidote to Methotrexate (poison/chemo)
Also used to treat Rheumatoid Arthritis
5-Fluorouracil
Pyrimidine antagonist
Inhibits thymidylate synthetase
Metabolites are incorporated into DNA and RNA
S phase-specific
Capecitabine
Pyrimidine antagonist
Oral prodrug of Fluorouracil
Colon and breast cancer treatment
Cytosine arabinoside
Pyrimidine antagonist
AKA Cytarabine and araC
araC–>araCMP–>araCTP which inhibits DNA synthesis and leads to breaks and mutations
Metabolic activation requires deoxycytidine
6-mercaptopurine
Purine antagonist
Interfere with DNA and RNA synthesis by inhibiting purine synthesis
S phase-specific
Activated by HGPRT
Metabolically inactivated by xanthine oxidase (cow’s milk)
6-thioguanine
Purine antagonist
Interfere with DNA and RNA synthesis by inhibiting purine synthesis
S phase-specific
Activated by HGPRT
Bleomycin
Anti-tumor AB/Anthracycline
Cuts DNA strands
Causes pulmonary fibrosis at large doses
Useful in combination regimens
Daunorubicin
Anti-tumor AB/Anthracycline
Binds to DNA topoisomerase II, cuts DNA, causes mutations and carcinogenic
SE: irreversible cardiac toxicity at high doses
Doxorubicin
Anti-tumor AB/Anthracycline
Has -OH group
Binds to DNA topoisomerase II, cuts DNA, causes mutations and carcinogenic
SE: irreversible cardiac toxicity at high doses
Paclitaxel
Mitotic spindle poison
Tx: metastatic ovarian and breast cancer
Comes from bark/leaves of yew tree
Blocks microtubule disassembly
Vinblastine
Mitotic spindle poison M phase-specific Inhibits microtubule polymerization SE: nausea, vomiting, bone marrow depression Tx: Hodgkin and other lymphomas Tubulin gene mutations cause resistance
Vincristine
Mitotic spindle poison
Binds to microtubules and stops mitosis
SE: no acute, mild bone marrow depression, muscle weakness
Tx: acute childhood leukemia, Hodgkin’s lymphoma
Tubulin gene mutations cause resistance
Irinotecan
Camptothecin
Blocks religation of single-strand break by binding to the cleavable complex of the DNA topoisomerase I and DNA
S phase-specific
Topotecan
Camptothecin
Blocks religation of single-strand break by binding to the cleavable complex of the DNA topoisomerase I and DNA
S phase-specific
Etoposide
DNA topoisomerase II inhibitor
Forms complex with topo2 and DNA
Tamoxifen
Comp inhibitor of estrogen Partial agonist low toxicity SE: hot flashes Tx: female and male breast and uterine cancers
Raloxifene
Selective estrogen response modulator
Tx: breast cancer in patients with osteoporosis
Lower risks of endometrial cancer and thrombosis than tamoxifen.
Anastrozole
Aromatase inhibitor
Inhibit conversion of androgens to estrogen
Blocks estrogen production in postmenopausal women
More effective than Tamoxifen for postmenopausal women
SE: joint pain, dec bone density
