Help
Options
Didn't know it?
click below
click below
Knew it?
click below
click below
Don't Know
Remaining cards (0)
Know
retry
shuffle
restart
0:00
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
AnticancerDrugs
lecture 5-6 goodman
| Question | Answer |
|---|---|
| 2 most important checkpoint controls in the cell cycle | G1-S checkpoint and the G2-M checkpoint |
| ca with shorter doubling time = easier to cure | leukemias respond better to anti-ca tx than colon carcinomas, which have a larger doubling time |
| types of normal cells that might be killed with chemotx | hair follicle cells, colonic crypts and bone marrow |
| antimetabolites kill cells that are in ___ phase during exposure | S phase |
| vinca alkaloids kill cells that are in ____ phase during drug exposure | M phase |
| phase non-specific drugs | kill cycling cells regardless of the phase they are in during exposure; cells will actually be killed in the S PHASE thus they are GROWTH-DEPENDENT drugs |
| first-order cell killing or logarithmic kill | when giving a dose of chemotx, 99% of cells will be killed with each round, fixed percentage die |
| What area of tumor has the slowest growing cells? | cells further away from the surface of the tumor aka in the core |
| Why use multi-drug therapy? | tumor cells can develop resistance by inducing production of a multi-drug resistance pump, for example, or duplicating genes like the DHFR gene |
| typical toxicities of anti-ca tx | GI: mucositis, nausea, cells dying in intestinal crypts // Heme: anemia, bleeding, myelosupression (give erythropoietin) // Hair: follicular cells die, hair falls out |
| types of drugs that interfere with DNA | antimetabolites, alkylating drugs, those which interrupt with topoisomerases |
| antimetabolite class | interfere with synthesis of normal nucleic acids; work as triphosphonucleotides to inhibit DNA polymerase or cause chain termination |
| purine analogs | mercaptopurine (hypoxanthine) and thioguanine (guanine) are analogs that work to deplete cells of purine nucleotides |
| 5-FU | S PHASE DRUG - activated to 5-FdUMP, which inhibits thymidylate synthase and starves cells of thymidine. resistance by altering TSase, causes myelosuppression and hair loss |
| capecitabine | prodrug that is metabolized to 5-FU in cells, ORAL DRUG |
| cytarabine | S PHASE DRUG, block btwn G1 and S - cytosine analog with arabinose instead of ribose, inhibits chain elongation, resistance by more cytidine deaminase. BEST tx for AML |
| methotrexate | S PHASE DRUG - analog of folic acid that binds with very high affinity to DHFR, depletes building blocks for DNA & RNA synthesis. use for leukemias & choriocarcinoma, resistance by upregulating salvage pathways |
| drug given to "rescue" pt after high doses of methotrexate | leucovorin - fully reduced folate coenzyme that helps to restore folic acid precursors in cells |
| hydroxyurea | erythrosuppressive that inhibits ribonucleoside reductase, useful for leukemias and lymphomas. also for sickle cell crises, very toxic |
| alkylating agents | cyclize to generate positively charged reactive intermediates that can be attacked by lone pairs of electrons on N or O of DNA forming crosslinked strands; cells enter S phase with damaged DNA and die |
| prototype of alkylating agents | mechlorethamine |
| cyclophosphamide | useful oral alkylating agent, is inactive until first pass through liver, can cause hemorrhagic cystitis |
| anthracyclines | planar tetracycline ring that intercalates btwn stacks of bases in DNA, reduced within cells and makes ROS, interferes with topoisomerase type II |
| adverse effects of alkylating agents | severe bone marrow suppression with high tendency for development of leukemias and lymphomas yrs later, mucositis, possible bacterial sepsis, amenorrhea and azoospermia |
| platinum complexes | non-classical alkylators that crosslink DNA, bifunctional agents that can react with guanines on same or different DNA strands; good use for solid tumors like testicles or ovaries |
| cisplatin | platinum complex; administered IV and is very nephrotoxic if not hydrated, ototoxicity and peripheral neuropathy, myelosuppression |
| unique adverse effect of anthracyclines | cardiomyopathy that is usually irreversible, occurs in up to 33% of pts taking these drugs |
| doxorubicin (Adriamycin) | anthracycline that treats wide range of tumors |
| bleomycin | G2 SPECIFIC DRUG: mixture of drugs that are complex glycopeptide antibiotics, chelate iron and copper and bind to DNA leading to redox radicals that cause multiple strand breaks and chr aberrations |
| adverse reactions of bleomycin | pulmonary fibrosis (Lance Armstrong didn't want to take it), one of the few drugs that is NOT TOXIC TO BONE MARROW |
| anti-topoisomerase agents | irinotecan (binds topo I, DS breaks during S phase metabolized to active drug SN-38, eliminated by glucuronidation) // etoposide (inhibits topo II causing DNA breaks) |
| antimicrotubule agents | act on microtubules to block cell progression through mitosis --- classes are taxanes and vinca alkaloids |
| vincristine and vinblastine | M PHASE AGENTS: bind tubulin alpha-beta heterodimers that stop formation of microtubules, cuase myelosuppression and neurotoxicity. vinblastine best for testicular ca, solid tumors |
| vincristine | primarily for childhood leukemias and lymphomas, worst side effect is peripheral neuropathy that can cause paresthesias or anesthesias |
| paclitaxel (Taxol) | binds preferentially to beta tubulin of existing microtubules and stops their disassembly, inhibits mitosis, good for breast and ovarian ca. can cause neuropathy |
| prednisone | synthetic glucocorticoid used for tx of leukemia |
| tamoxifen | SERM or selective estrogen receptor modulator; binds competitively with estrogen on ER+ breast ca cells; approved for prophylaxis of ER-sensitive breast ca in women with BRCA1 or 2 gene mutations |
| how to reduce the endogenous sex steroid production when treating hormone-sensitive breast or prostate ca | oophorectomy/orchiectomy and treatment with a GnRH analog |
| anastrozole | aromatase inhibitor that stops peripheral estradiol production from adipose tissue to as to starve the hormone-sensitive breast ca |
| flutamide | anti-androgen used in combo with GnRH agonist to safely cause a chemical castration for tx of prostate ca |
| leuprolide | potent GnRH agonist, causes a transient release of FSH and LH then strong feedback inhibition, resulting in cessation of testosterone production |
| drugs ending in -inib | small molecules that INhIBit tyrosine kinases |
| drugs ending in -umab | hUManized ABs that are altered genetically so as not to produce an anti-mouse neutralization response |
| drugs ending in -ximab | "X out the mouse Ab", drugs that are chimerized to contain human Fc region |
| imatinib (Gleevec) | specific inhibitor of bcr-abl oncogene for tx of chronic myelogenous leukemia (CML) |
| bevacizumab (Avastin) | monoclonal Ab against VEGF, inactivates it and solid tumors fail to grow due to insufficient vascularization. side effects include slow wound healing and increased bleeding |
| interleukin-2 | stimulates the generation of killer T cells that attack malignant metastatic melanoma and other leukemias |
| thalidomide | downregulates IL-6, VEGF and TNF synthesis, important in the tx of multiple myeloma. also now for leprosy and MS |
| bortezomib | inhibits the proteasome that would normally destroy IkappaB and free it from NFkappaB so it can promote growth genes within the nucleus |
| Tretinoin | is ATRA that binds to RAR, which dimerizes with RXR to displace a transcription inhibitor and promote differentiation of myeloid precursors; first line tx for acute promyelocytic leukemia (APL); ATRA syndrome - pulmonary infiltration and resp distress |
| colony stimulating factors | inreases the # of nl blood cells, allowing more aggressive use of cytotoxic agents with fewer effects on bone marrow cells; include erythropoietin, granulocyte CSF and granulocyte-macrophage CSF |
Created by:
sirprakes
Popular Pharmacology sets