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Anticancer drugs
| Question | Answer |
|---|---|
| What is the Log-Kill Hypothesis of Anticancer drugs? | Anticancer drugs follow first-order kinetics: they kill a fixed PERCENTAGE of tumors cells, NOT a fixed NUMBER (One reason for drug combinations) |
| Cell-cycle specific anticancer drugs work on which type of cell growth factor? | HIGH GROWTH FACTOR (rapidly dividing cells, including tumor cells as well as normal cells of the bone marrow) |
| Cell-cycle nonspecific drugs work on which type of cell growth fraction? | HIGH and LOW growth fraction |
| What are the cell cycle phases? | G1 S phase G2 M phase |
| What is the anticancer that work on M phase? | Microtubule inhibitors (Taxenes + Vinca alkaloids) |
| What are the anticancer drug groups that work on S phase? (2) | 1. Antimetabolites 2. Topoisomerase inhibitors |
| What are the anticancer drug groups that work on G2 phase? (2) | 1. Topoisomerase inhibitors 2. Bleomycin |
| What are the anticancer drug groups that are cell-cycle independent? (2) | 1. Platinum compounds (Cisplatin, Carboplatin, Oxaliplatin) 2. Alkylating agents |
| Toxicity of Cisplatin? | Nephrotoxicity and Ototoxicity |
| Toxicity of Bleomycin | Pulmonary fibrosis |
| Toxicity of Doxorubicin | Cardiotoxicity |
| Toxicity of Vincristine? | Peripheral neuropathy |
| Toxicity of Cyclophosphamide? | Hemorrhagic cystitis |
| What is the target of Imatinib? | BCR-ABL |
| What is the target of Cetuximab? | ErbB1 |
| What is the target of Trastuzumab? | ErbB2 (HER2/neu) |
| What is the target of Bevacizumab? | VEGF-A |
| What is the target of Sorafenib? | RAF kinase |
| What are the receptors expressed by breast cancers? | ER+ (estrogen receptor) HER2+ PR (progesterone receptor) |
| Aldesleukin (IL2) echanism and usage | Mechanism: INCREASE lymphocyte differentiation and NKs Usage: Renal cell carcinoma and Metastatic melanoma |
| Interleukin 11 mechanism and usage | Mechanism: INCREASE platelet formation Usage: Thrombocytopenia |
| Filgrastim (G-CSF) mechanism and usage | Mechanism: INCREASE granulocyres Usage: Marrow recover |
| Sargramostim (GM-CSF) mechanism and usage | Mechanism: INCREASE granulocytes and Macrophagges Usage: Marrow recovery |
| Erythropoietin and usage | Usage: Anemias, (esp w renal failure) |
| Thrombopoietin usage | Thrombocytopenia |
| Cyclophosphamide MOA | (prodrug, alkalyting agent) Cross links DNA (attack at guanine N7) |
| Doxorubicin MOA | Generate free radicals, intercalate in DNA —> breaks DNA —> DECREASE replication, Inhibit Topoisomerase 2 |
| Methotrexate MOA | (Folic acid analog) Inhibits dihydrofolate reductase —> DECREASE dTMP —> DECREASE DNA synthesis |
| 5-Fluorouracil MOA | (Pyrimidine analog) Activated to 5-FdUMP —> thymidylate synthase inhibition —> DECREASE DNA synthesis |
| 6-Mercaptopurine (Azathioprine) | (Purine analog) DCREAE purine synthesis Bioactivated by HGPRT (Inactivated by xanthine oxidase) |
| VIncristine & Vinblastine MOA | Bind b- tubulin and inhibit its polymerization into microtubules —> prevent mitosis spindle formation (Used for Hodgkin) |
| What are the Calcineurin inhibitors? (2) | 1. Cyclosporine 2. Tarcolimus Calcineurin dephosphorylates NFAT (Nuclear Factor of Activated T cells). Dephosphorylated NFAT enters the nucleus and turns on IL-2 transcription → IL-2 drives T cell proliferation. |
| S/E of Calcineurin inhibitors? (2) | 1. Nephrptoxicity (contricts afferent arteriole which decrease GFR) 2. Gingival overgroath |
| Mycophenolate MOA | inhibits IMP dehydrogenase--> decrease GMP (decrease purine syntehsis) |
| Azathioprine MOA | inhibits purine synthesis (A prodrug to 6- Mercaptopurine) |
| Anti-D immunoglobulin MOA and its uses | Human IgG antibodies to red cell D antigen (rhesus antigen) use: administer to Rh- antigen mother within 72 hours of delivery of Rh-positive baby to prevent hemolytic disease of newborn in subsequent pregnancy |
| Palivizumab MOA | Blocks RSV protein (fusion protein) RSV = Respiratory syncytial virus |
| Rituximab MOA | Non-hodgkin lymphoma: binds to surface protein (CD20) |
| Basiliximab MOA | Prevent organ rejection: IL2 receptor antagonist |
| Interferon alpha use | Hep B+C , leukemias, melanoma |
| Inteferon betta use | Multiple sclerosis |
| Inteferon gamma use | Chronic granulomatous disease --> increase TNF |
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DVD27