Fun 3 Flashcards
Cytarabine
Antimetabolite (S-phase specific)
Converted to triphosphate and incorporated into DNA
Treat AML
Resistance: Increased cytidine deaminase, decreased deoxynucleotide kinase and altered DNA polymerase
5-Fluorouracil
Antimetabolite (S-phase specific)
Metabolized to 5-FdUMP - Inhibits thymidylate synthase
Used for solid tumors (pancreas, GI and liver)
Toxicity: Neurotoxicity
Resistance via altered thymidylate synthase
Methotrexate
Antimetabolite
Inhibits DHFR (starves cell of both purines and pyrimidines)
Causes accumulation of DHF-polyglutmate, directly blocking purine synthesis
Treat carcinomas, leukemias and lymphomas
Toxicity: Pneumonitis and cirrhosis
Toxicity reduced with leucovorin rescue
Resistance: DHFR amplification, altered DHFR, decreased drug import or increased salvage
Leucovorin
Fully reduced folate
Rescues normal cells from methotrexate toxicity
Mechlorethamine
Alkylating agent (phase non-specific)
Bifunctional agent
M in MOPP for Hodgkin’s lymphoma treatment
Can cause secondary leukemia
Cyclophosphamide
Alkylating agent
Less reactive than mechlorethamine
Requires p450 metabolism in liver (reduces toxicity; allows oral admin.)
Used for leukemia and lymphoma
Toxicity: Hemorrhagic cystitis if patient not hydrated
Can cause secondary leukemia
Cisplatin
Platinum complex - “nonclassical” alkylator
Bifunctional agent
Treat testicular cancer and other solid tumors
Nephrotoxicity if patient dehydrated
Doxorubicin
Anthracycline Intercalates into DNA - Redox causes DNA damage Inhibits topo II Treat solid tumors Can cause cardiomyopathy
Bleomycin
DNA binder(G2-specific)
Chelates copper and iron - Redox damages DNA
Treat germ cell tumors
Can cause pulmonary fibrosis
Irinotecan
Topo I inhibitor (S-phase specific)
Treat solid tumors
Activated to SN-38 - Can cause leukopenia
SN-38 glucuronidated by UGT1A1
Genetic defect in UGT1A1 causes nausea and leukopenia
Etoposide
Topo II inhibitor (S-phase specific)
Treat leukemia and lymphoma
Can cause secondary leukemia
Vincristine
Prevents microtubule polymerization (M-phase specific)
Directly binds tubulin heterodimers
Can cause peripheral neuropathy
Treat leukemia and lymphoma
Vinblastine
Prevents microtubule polymerization (M-phase specific)
Directly binds tubulin heterodimers
Neurotoxic
Treat solid tumors
Paclitaxel
Inhibits microtubule depolymerization
Bind to beta tubulin
Treat breast and ovarian cancer (also lung and head/neck)
Can cause “stocking glove” neuropathy
Prednisone
Glucocorticoid
Treat leukemias by activating apoptosis
Tamoxifen
Selective estrogen receptor modulator
Treat breast cancer (can be prophylactic)
Better for post-menopausal women (less endogenous estrogen)
Anastrozole
Aromatase inhibitor
Treat estrogen-sensitive breast tumors
Prevents post-menopausal women producing estrogen from extra-ovarian tissue
More specific than early agents (doesn’t block corticosteroid pathway)
Flutamide
Testosterone receptor antagonist
Treat prostate cancer
Used in combination with GnRH agonist
Leuprolide
GnRH agonist
Treat prostate cancer
Cause transient release of FSH and LH (blocked by flutamide)
Long-term feedback inhibition of testosterone release
Daily subQ admin.
Imatinib
Bcr-Abl inhibitor Treat CML (t9:22) Diffuses into cell to inhibit tyrosine kinase
Bevacizumab
VEGF inhibitor
Humanized monoclonal antibody
Treat colorectal cancer
Can increase bleeding and cause slow wound healing
Interluekin-2
Stimulates generation of killer T-cells
Approved for melanoma; active for other tumors and leukemia
Bortezemib
Proteasome inhibitor
Stabilizes IkB - Inhibits NFkB preventing growth
Treats multiple myeloma
Tretinoin
All-trans retinoic acid (ATRA)
Cofactor of RAR-RXR dimer - Displaces repressor of differentiation
APL has RAR-PML mutation decreasing APL affinity for dimer
Pharmacologic doses overcomes APL mutation
Can cause pulmonary distress via inflammation
Thalidomide
Inhibits angiogenesis and stimulates immune system (blocks VEGF, TNF and IL-6 production)
Treat multiple myeloma
Can cause birth defects
Colony-stimulating factors
EPO, G-CSF and GM-CSF
Promote growth of bone marrow cells to prevent toxic effects of cytotoxic agents - Attenuate myelosuppression and anemia
