FPP-Drugs Flashcards
Alkylating Agents
Introduce alkyl groups into DNA, causes crosslinks and strand breaks
cell-cycle non-specific:
Mechlorethamine, Carmustine
cycle specific, phase non-specific:
Cyclophosphamide
Sides: bone marrow suppression, GI effects, alopecia
Mechlorethamine
Alkylating agent
cell-cycle non-specific
limited use today, highly reactive
Lymphomas
Cyclophosphamide
Alkylating agent
Prodrug, activated by P450s
cycle-specific, phase non-specific, oral, poor CNS
side product-> bladder toxicity (treated w Mesna)
broad spectrum, wide uses
Carmustine
Alkylating agent
cycle non-specific
crosses blood brain barrier
used for brain tumors, multiple myeloma, melanoma
Antimetabolites
Most effective in rapidly proliferative
S-phase specific
Analogs of compounds for nucleic acid biosynthesis
Mercaptopurine, Methotrexate, Hydroxyurea, Fluorouracil, Cytarabine
Methotrexate
Folate analog
Binds DHFR and prevents FH4 synthesis
sides: GI epithelial damage, bone marrow suppression, renal tubular necrosis, displaces other albumin-bound drugs
Acute lymphocytic leukemia (ALL), Choriocarcinoma (can cure)
Leucovorin
folate rescue
with high-dose Methotrexate, this can be used to rescue normal cells
Fluorouracil
5-FU
Inhibits RNA synthesis and DNA synthesis via thymidylate synthase
Sides: nausea, anorexia, diarrrhea, myelosuppression
Uses: GI cancers (1st), colon, breast, basal cell carcinoma
Cytarabine
Pyrimidine (cytidine) analog competes for phosphorylation
causes DNA chain termination
Sides: myelosuppression, neurotoxicity
Phase-specific dose kinetics (continuous infusion)
Acute leukemias
Mercaptopurine
purine analog, inhibits RNA and DNA synthesis
Sides: bone marrow supp, vomiting, nausea, anorexia, Jaundice
Acute leukemias
TPMT polymorphisms in some pts need to adjust dose or not use
Hydroxyurea
Inhibits ribonucleotide reductase, blocks DNA synthesis
arrests cells at G1-S
Uses: granulocytic leukemia
Sides: hematopoietic depression, GI issues
Vinca Alkaloids
Bind tubulin, inhibits microtubule and mitotic spindle assembly
Vincristine, Vinblastine
Vinblastine
Vinca Alkaloid
Sides: strongly myelosuppressive, epithelial ulcerations
Use: lymphomas, breast cancer
Vincristine
Vinca Alkaloid
Sides: less bone marrow supp, alopecia, neuromuscular abnormalities, peripheral neuropathy
Use: acute lymphocytic leukemia, lymphomas, Wilm’s tumor, neuroblastoma, etc
Taxanes
Enhances assembly and stability of microtubules, binds tubulin
Arrests in G2-M (radiosensitizer)
Paclitaxel
Paclitaxel
Taxane
use: refractory ovarian cancer, breast cancer
Sides: leukopenia, peripheral neuropathy, myalgia
Doxorubicin
Intercalates in DNA, distorts, causes lipid preoxidation and free radicals, binds DNA+topoisomerase II
cycle-specific, phase non-specific
among most active anti-tumor
wide spectrum, lymphomas, breast, ovary, small cell lung
also anti-angiogenic
sides: cardiomyopathy, bone marrow supp, alopecia, GI effects
Bleomycin
iron-containing glycopeptides bind to DNA, causes oxidative damage, strand breaks
Needs chelated Fe
G2-phase specific
germ cell tumors, head, neck, lung, lymphomas
sides: minimal myelosupp, pulmonary toxicity, skin vesiculation/hyperpigment
Etoposide
Stabilizes DNA-topoisomerate II
Arrests G2-M interface
use: lymphomas, acute leukemia, small cell lung, testis
sides: leukopenia, nausea, vomiting, diarrhea, alopecia
Filgrastim
Granulocyte colony stimulating factor
limits chemo-induced neutropenia
sides: bone pain
Trastuzumab
HER2 receptor antibody
use: breast cancer that ovexpresses HER2
sides: cardiomyopathy (reversible), hypersensitivity, infusion rxn
Cisplatin
Platinum coordination complex
actived to cause DNA crosslinks
cell-cycle-specific, phase non-specific
testicular cancer, ovarian, head, neck, bladder, small cell lung, esophagus, etc
sides: nephrotoxicity, ototoxicity, peripheral neuropathy, electrolyte probs, nausea, myelosupp
Procarbazine
Activated by liver to methylating agent, causes chromosomal damage
atypical alkylating agent
Hodgkin’s Lymphoma
sides: myelosupp, nausea, vomiting
Prednisone
Binds steroid receptors arrests in G1 depress growth-related genes induces nucleases-> cell-lysis lymphoma, leukemia, breast cancer also anti-emetic and anti-inflammatory, immunosuppressive, weight gain, fluid retiention, psychological
Tamoxifen
non-steroidal anti-estrogen receptor in breast tissue
cytostatic (tumor regrows when removed)
use: post-menopausal breast cancer, pre-menopausal metastatic breast CA, breast CA prohylaxis
Activated by CYP2D6
sides: nausea, hot flashes, fatigue, bone pain
Letrozole
blocks conversion of androgens to estrogens by inhibiting aromatase (CYP19)
1st line for post-menopausal or metastatic breast CA
Better effects than Tamoxifen, sides similar
Leuprolide
GnRH analog
after initial surge, decreases LH/FSH, which decreases testosterone
use: prostate CA
sides: hot flashes, impotence
Flutamide
non-steroidal anti-androgen, blocks androgen receptors
use: metastatic prostate CA
sides: gynecomastia, diarrhea, hepatotoxicity
Multi-drug resistance (MDR)
ATP-dependent drug efflux pumps (P-glycoprotein, MRP)
Vincristine, Vinblastine, Doxorubicin, Bleomycin, Etoposide, Paclitaxel
Natural Products
Vinblastine, Vincristine, Paclitaxel
Anti-tumor Antibiotics
Doxorubicin, Bleomycin, Etoposide
Misc Agents
Cisplatin, Procarbazine
Biological response modifiers
Filgrastin, Trastuzumab
Hormones and Antagonists
Prednisone, Tamoxifen, Letrozole, Leuprolide, Flutamide
