Anti-Neoplastics Flashcards
Cell cycle-nonspecific
- Exerts cytotoxicity in a nonspecific manner - kills cells in any stage of cell cycle (even G0) - kills normal and neoplastic cells to the same extent Examples: alkylating agents
Cell cycle-specific, phase-specific
- More active at specific phase of cell cycle
- Some selectivity of action ( more cytotoxic for neoplastic cells)
- given by continuous infusion of in frequent small doses
- *G1**: Predisone
- *S**: Cytarabine, 5FU, MTX, 6MP, Hydroxyurea
- *G2**: Bleomycin, etoposide, Paclitaxel
- *M**: Vinbastine, vincristine
Cell cycle-specific, phase-nonspecific
- Preferential killing of proliferating neoplastic cells BUT without regard for phase of cell cycle - administered in large doses to take advantage of their sparing effect on normal cells in G0 Ex: cyclophosphamide, cisplatin, Doxorubicin
sequential blockade
Simultaneous action of two inhibitors acting on different steps of a linear metabolic pathway
concurrent inhibition
inhibitors block two separate pathways that lead to same end product
rescue
High doses of MTX necessary to bind DHFR. Rescue normal cells with leucovarin ( folate coenzyme that does not require reduction by DHFR). Normal cells have increased capacity to bring in leucovorin
complementary inhibition
One drug affects the function of an end product, the other drug affects the synthesis of that end product
Synchronization
Synchronize cells so that they are in one phase and then use drug that is specific for that phase
recruitment
Mobilizing slowly proliferating or non-proliferating cells to more rapid proliferation ( bring cells out of G0 into cell cycle)
Mechlorethamine
Mechanism: Bi-functional alkylating agent that produces DNA crosslinks
Cell Cycle: phase non-specific
Use: Hodgkin’s and non-Hodgkin’s lymphoma
Toxicity: Hematopoiesis suppression, damage to intestinal mucosa, N/V, alopecia
Cyclophosphamide
Mechanism: Activated by cyt. P450 Cell Cycle: phase non-specific
Use: very broad spectrum, Hodgkin’s and non-Hodgkin’s lymphoma, mutiple myeloma, neuroblastoma, leukemias. Carcinoma of the endometrium, breast, lung
Toxicity: May cause sterile hemorrhagic cystitis ( Prevented with Mesna)
Carmustine
Mechanism: Introduce alkyl groups into DNA. Highly lipophilic– rapidly crosses blood-brain barrier
Cell Cycle: Non-specific
Use: brain tumors, multiple myeloma, melanoma
Toxicity: Hematopoiesis suppression, N/V, alopecia
Methotrexate
Mechanism: metabolite binds to dihydrofolate reductase (DHFR) and prevent formation of tetrahydrofolate (THF) - use is followed with rescue with Leucovorin
Cell Cycle: S phase specific
Use: ALL; choriocarcinoma
Toxicity: Binds serum albumin so avoid use with other drugs that will displace it from albumin. Intestinal epithelium, bone marrow suppression, renal tubular necrosis
5 fluorouracil
Mechanism: Activated in cells to FUTP ( inhibits RNA synthesis) and FdUMP ( interferes with thymidylate synthetase –> DNA synthesis)
Cell Cycle: S- phase specific
Use: Carcinoma of the stomach, colon, pancreas, ovary, head, neck, breast, bladder. Basal Cell carcinoma
Toxicity: nausea, anorexia, diarrhea, delayed myelosuppression
Cytarabine
Mechanism: cytidine analog that competes with cytidine for all 3 phosphorylation steps to dCTP. competes with dCTP for incorporation into DNA
Cell Cycle: S-phase specific
Use: Acute leukemia (AML)
Toxicity: Myelosuppression and neurotoxicity
Mercaptopurine
Mechanism: Purine analog that is converted in cells to ribonucleotide that inhibits RNA and DNA synthesis
Cell Cycle: S-phase
Use: acute leukemia
Toxicity: bone marrow depression, N/V, anorexia, jaudice
Hydroxyurea
Mechanism: inhibits ribonucleotide reductase ( blocks DNA synthesis)
Cell Cycle: S-Phase (G1/S interface)
Use: Chronic granulocytic leukemia, head and neck cancer. Useful w/ radiation
Toxicity: Hematopoietic depression, GI disturbances
Vinblastine
Mechanism: Binds to tubulin, inhibits formation of microtubules and mitotic spindle
Cell Cycle: M-phase
Use: Hodgkin’s and non-Hodgkin’s lymphoma, breast cancer
Toxicity: Strongly myelosuppressive, epithelial ulcerations
Vincristine
Mechanism: binds to tubulin, inhibits formation of microtubules and mitotic spindle
Cell Cycle: M- phase
Use: ALL, lymphomas, Wilm’s tumor, nueroblastoma
Toxicity: alopecia, neuromuscular abnormalities (peripheral neuropathies), less bone marrow suppression
Paclitaxel
Mechanism: enhances assembly and stability of microtubules by binding to Beta subunit of tubulin
Cell Cycle: G2 phase (G2/M interface)
Use: refractory ovarian cancer; breast
Toxicity: Dose limiting leukopenia, peripheral neuropathy, myalgia/ Arthralgia
Doxorubicine
Mechanism: 1) Prevents DNA/RNA synthesis by intercalating between DNA bp–> distorts helix. 2) causes lipid peroxidation and free radical generation. 3) binds to DNA and topoisomerase II
Cell Cycle: phase non-specific
Use: Hodgkin’s and non-Hodgkin’s lymphoma, breast, ovary, small-cell lung
Toxicity: Cardiomyopathy, bone marrow depression, alopecia, GI disturbances - antiangiogenic properties
Bleomycin
Mechanism: glycopeptides that bind DNA–> causes oxidative like damage to DNA that leads to strand breaks
Cell Cycle: specific for M phase
Use: germ cell tumors of testes and ovaries, head, neck, lung, lymphomas
Toxicity: dose-related pulmonary toxicity, vesiculation of the skin, skin hyperpigmentation, minimal myelosuppression and immunosuppression Lung and skin have lowest levels of Bleomycin hydrolase
Etoposide
Mechanism: Stabilizes DNA topoisomerase II complexes–> ds DNA breaks
Cell Cycle: late G2 phase (late S)
Use: lymphomas, acute nonlymphocytic leukemia, small cell carcinoma of lung, testicular tumors
Toxicity: Leukopenia, N/V, diarrhea
Filgrastim
Mechanism: stimulates granulocytes (neutrophils) production by marrow
Cell Cycle:
Use: give after myelosuppression to speed neutrophil recovery (used to limit neutropenia) Toxicity: bone pain
