Anti-neoplastic drugs Flashcards
what are chemotherapeutic drugs?
destroy or injure invading organisms or tissues
include: antimicrobial, antiparasitic and antineoplastic drugs
objective is “level the playing field” so body’s own mechanisms have an opportunity to prevail against invaders
what % of CAs are cured? what % are cured using radiation and surgery? using antineoplastic drugs?
50% of CA pts are cured
35% are cured using radiation and surgery
15% are cured using antineoplastic drugs
3 ways antineoplastic drugs may distinguish CA cells from normal cells?
- rate of growth and proliferation
- consumption of selected nutrients
- consumption of O2
what types of cells are generally affected by antineoplastic drugs and why?
bone marrow cells (anemia, leukopenia, infxns)
hair follicles (alopecia)
buccal mucosa (stomatitis)
gonads (impotence)
embryonic tissue (teratogenicity)
all affected b/c they divide rapidly and consume lg amounts of nutrients and O2
what two reasons are antineoplastic drugs administered?
for purpose of curing the disease
if cure is unattainable, then goal is palliation and increased longevity
3 times when antineoplastic drugs are indicated?
neoplasm is known to be sensitive to the drug
neoplasm has metastasized to the point that surgery and radiation are not practical
surgery and radiation require chemo supplementation
why do treatments sometimes involve following surgery and radiation with chemo?
b/c by reducing tumor burden the remaining CA cells enter the proliferation stage and then are more susceptible to antineoplastic drugs
are antineoplastic drugs subject to resistance?
YES resistance can develop
how are most antineoplastics delivered?
most delivered via IV so as to optimize concentration
primary resistance vs acquired resistance?
primary: absence of response on 1st exposure to contemporary antineoplastic drugs among specific CAs (malignant melanoma, brain CA, renal cell CA)
acquired: develops in response to repeated exposure to selected antineoplastic drugs (CA cell mutation mitigate drug effects, enhanced drug efflux via P-glycoprotein)
what is tumor lysis syndrome?
when is it esp common? complications? prevented by/treated by? if not precipitated by antineoplastic drugs what is it called?
SEs caused by debris from dead CA cells
common when treating leukemia and lymphoma
complications: hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, hyperuricosuria
may be prevented/treated with allopurinal (inhibit uric acid synthesis) and IV fluids
referred to as Spontaneous Tumor Lysis Syndrome if not precipitated by antineoplastics
how many CA cell are there usu by the time dx? what is the MC outcome if untreated? outcome of infrequent chemo? outcome of aggressive and prolonged chemo? combo of what two things hastens cure?
usu abundant CA cells by the time dx no treatment usu = death infrequent chemo may delay death aggressive and prolonged chemo may result in cure chemo + surgery may hasten cure
3 methods of antineoplastic classification?
- cell cycle
- MOA
- chemical classification
what are cell cycle antineoplastics?
cell cycle specific agents which selectively inhibit one or more phases in the CA cell reproductive cycle
what are the MOAs which some antineoplastics may utilize?
alkylating agents
microtubule inhibitors
antimetabolites
what are two chemical classifications of antineoplastics?
platinum analogues
steroid inhibitors
7 common MOAs of antineoplastics?
alkylating agents platinum analogs antimetabolites microtubule inhibitors antibiotic-like drugs hormonal inhibitors monoclonal antibodies
how do alkylating agents work?
introduce alkyl group to DNA which prevents replication (chlorambucil, procarbazine)
how do antimetabolites work?
interfere w/formation of DNA or RNA by preventing access to key metabolic components
how do microtubule inhibitors work?
prevent separation of chromosomes (methotrexate- folic acid antagonist; 6 mercaptopurine, 5-fluorouracil)
how do antibiotic-like drugs work?
break DNA during replication (doxorubicin)
how do hormonal inhibitors work?
reduce natural stimulation of tissue growth and proliferation (tamoxifen- estrogen antagonist)
additional emerging antineoplastic MOAs?
signal transduction inhibitors differentiation agents anti-angiogenic drugs hypoxia inducing drugs cytoprotective drugs biologic response modifiers genetic modifiers
how do signal transduction inhibitors work?
inhibit chem signals to cell for growth and proliferation
how do differentiation agents work?
hasten cell maturation past reproductive stage
how do anti-angiogenic drugs work?
inhibit vascularization of tumors
how do hypoxia inducing drugs work?
increase O2 consuming rxns in tumors
how do biologic response modifiers work?
enhance immunologic and other self-defense mechanisms
how do genetic modifiers work?
replace CA causing genomes w/normal genomes
10 alkylating agents?
cyclophosphamide mechlorethamine carmustine lomustine isophamide temozolamide dacarbazine cisplatin carboplatin oxaliplatin
class of cyclophosphamide/cytoxan?
antineoplastic, alkylating agent
MOA of cyclophosphamide/cytoxan?
inhibits DNA replication, transcription of RNA and nucleic acid fxn
distinguishing characteristics of cyclophosphamide/cytoxan?
PO and IV
nephrotoxicity can occur
SEs of cyclophosphamide/cytoxan?
nausea, vomiting, diarrhea, abd pn, ALL, hodgkin’s dz, non-hodgkin’s lymphoma, breast, ovarian, lung CAs, multiple myeloma, sarcomas, CLL
9 anti-metabolite agents?
methotrexate 6-mercaptopurine 6-thioguanine fludarabine cladribine 5-fluorouracil capecitabine cytarabine gemcitabine
class of methotrexate/MTX
antineoplastic, anti-metabolite, DMARD (disease modifying anti-rheumatic drugs), immunosuppressive
MOA of methotrexate/MTX
competitively inhibits dihydrofolate reductase
how to administer methotrexate/MTX? route of elimination
administer PO, IV, IM, PR
renal excretion primarily
indications for methotrexate/MTX?
lung, breast CA, leukemia, hodgkin’s/non-hodgkin’s lymphoma, cutaneous T cell lymphoma, head and neck CA, osteosarcoma
SEs of methotrexate/MTX?
n/v/d, stomatitis, alopecia, myleosuppression, peripheral neuropathy, hepatotoxicity
what two anti-metabolites are bogus purines?
6-mercaptopurine and thioguanine
bogus purines formed by addition of sulhydril groups to the nitrogen in the 6 position, these compounds then enter and block the pathway that would normally lead to the formation of nucleotides and DNA
4 abx-like drugs?
doxorubicin
dactinomycin
daunorubicin
bleomycin
class of doxorubicin/adriamycin?
antineoplastic, anthracyclin, antibiotic-like agent
MOA of doxorubicin/adriamycin?
inhibits DNA and protein synthesis
doxorubicin/adriamycin: narrow or broad spectrum? how to administer? toxicity?
most efficacious for broadest spectrum
rapid IV or risk tissue necrosis at site of injection
cardiotoxicity limits usefulness
4 microtubule inhibitors?
vincristine
vinblastine
paclitaxel (taxol)
docetaxel
class of paclitaxel/taxol?
antineoplastic microtubule inhibitor, chemotherapy
MOA of paclitaxel/taxol?
reversibly binds to microtubule preventing cell division
how to administer paclitaxel/taxol? sourcing?
IV
originally sourced from Pacific Yew tree now extracted from needles of more abundant species
indications for paclitaxel/taxol? SEs?
indications: advanced ovarian cancer, metastatic breast CA
SEs: n/v, anorexia, arthralgia, alopecia, fever, chills, sore throat
9 steroid hormones + antagonists?
prednisone tamoxifen aminoglutethimide anastrozole letrozole exemestane megesterol acetate leuprolide goserelin
class of tamoxifen/valodex?
antineoplastic, estrogen antagonist
MOA of tamoxifen/valodex?
binds to E receptor, blocks RNA synthesis
how to administer tamoxifen/valodex? where does it work and how specifically?
PO
selective competitive antagonist in breast tissue
partial agonist in uterine tissue
tamoxifen/valodex is standard tx for what? can also tx what other benign condition? increases the risk for what?
standard tx for early breast CA
can tx hot flashes and other menopausal sxs
increases the risk for uterine CA
4 monoclonal antibody drugs?
trastuzumab
rituximab
bevacizumab
cetuximab
class of trastuzumab/herceptin?
antineoplastic, monoclonal antibody
MOA of trastuzumab/herceptin?
binds to HER2 sites in breast CA tissue inhibiting proliferation of cells that over-express the HER2 protein
can trastuzumab/herceptin cross the BBB? how to administer?
too large to cross BBB
administer via IV
indication for trastuzumab/herceptin? SEs?
indication: metastatic breast CA
SEs: fever, chills, cardiotoxicity esp w/anthracycline
6 “other” chemo agents?
cisplatin carboplatin oxaliplatin irinotecan topotecan etoposide
what is cisplatin/platinol? what is it used to tx?
platinum based drug used to tx various cancers such as sarcomas, some carcinomas, lymphomas and germ cell tumors
it was the first of it’s class
MOA of cisplatin/platinol and platinum containing drugs?
platinum complex w/in acts w/DNA of rapidly dividing cells, binding to and causing cross-linking of DNA–> triggers apoptosis of cell
class of cisplatin/platinol?
antineoplastic, platinum compound
MOA of cisplatin/platinol?
inhibits DNA and RNA replication
how to administer cisplatin/platinol? toxicity?
IV
highly nephrotoxic
indications of cisplatin/platinol? SEs?
indications: solid tumors, bladder carcinoma, metastatic testicular carcinoma
SEs: n/v, rash, high frequency hearing loss, tinnitus, possible bone marrow suppression, possible anaphylaxis
6-mercaptopurine and 5-fluorouracil are both anti-metabolites that affect what phase of the cell cycle?
S phase
paclitaxel, a microtubule inhibitor, affects what phase of cell division?
M phase
2 purines of DNA? 3 pyrimidines of DNA/RNA?
“pure as AG (gold)”: adenosine, guanine
“CUT the pie”: cytosine, uracil, thymine
