Chemo drugs 0504 Flashcards
antimetabolites
methotrexate 5-fluorouracil 6-mercaptopurine 6-thioguanine cytarabine cladribine
*ALL ARE S-PHASE SPECIFIC
methotrexate (MTX) MOA
folic acid analog that inhibits dihydrofolate reductase
decrease dTMP
decrease DNA
decrease prot synth
MTX cancer USE
leukemia
lymphoma
sarcoma
choriocarcinoma
MTX non-neoplastic USE
abortion
ectopic preg
rheumatoid arthritis
psoriasis
MTX TOX
- myelosuppression
- macrovesicular fatty change of liver
- mucositis
- teratogenic
what reverses MTX myelosuppression?
leucovorin (folinic acid) rescue
aka N5 formyl-THF
5-fluorouracil (5FU) MOA
pyrimidine analog that is bioactivated to 5F-dUMP, which covalently complexes folic acid.
COMPLEX inhibits thymidylate synthase.
decrease dTMP
decrease DNA
decrease prot synth
5FU USE
colon cancer and other solid tumors.
topical for basal cell carcinoma.
which drug works in synergy with MTX?
5-fluorouracil
5FU TOX
- myelosuppression
2. photosensitivity
what reverses 5FU myelosuppression?
thymidine
NOT LEUCOVORIN
6-mercaptopurine (6MP) MOA
purine (thiol) analog that decreases de novo purine synth
what activates 6MP?
HGPRTase
6MP USE
leukemia
lymphoma (NOT CLL or Hodgkin)
6MP TOX
bone marrow, GI, liver
6MP metabolism
metabolized by xanthine oxidase
*increased tox with allopurinol
what increases 6MP tox?
allopurinol
6-thioguanine (6TG) MOA
purine (thiol) analog that decreases de novo purine synth
what drug has the same MOA as 6TG?
6-mercaptopurine
6TG USE
acute lymphoid leukemia (ALL)
6TG TOX
BM depression, liver.
*can be given with allopurinol
cytarabine (ara-C) MOA
pyrimidine analog - inhibits DNA polymerase
which antimetabolites are pyrimidine analogs?
5-fluorouracil
cytarabine
ara-C USE
AML
ALL
high-grade NON-Hodgkin lymphoma
ara-C TOX
leukopenia
thrombocytopenia
megaloblastic anemia
cladrabine MOA
purine analog that is resistant to degradation by adenosine deaminase - can reach high intracellular concs and cause DNA strand breaks
cladrabine USE
hairy cell leukemia - complete remission
antitumor antibiotics
dactinomycin
doxorubicin, daunorubicin
bleomycin
etoposide, teniposide
dactinomycin (actinomycin D) MOA
intercalates in DNA
dactinomycin USE
Wilms tumor
Ewings sarcoma
rhabdomyosarcoma
(childhood tumors)
dactinomycin TOX
myelosuppression
doxorubicin (adriamycin) and daunorubicin MOA
generate FREE RADICALS that noncovalently intercalate in DNA
DNA breaks = decreased replication
doxorubicin (adriamycin) and daunorubicin USE
Hodgkin lymphomas
myeloma
sarcoma
solid tumor (breast, ovary, lung)
doxorubicin (adriamycin) and daunorubicin TOX
dose-related DILATED CARDIOMYOPATHY.
myelosuppression.
alopecia.
what prevents cardiotoxicity with doxorubicin (adriamycin) and daunorubicin?
dexrazoxane - iron chelating agent
bleomycin MOA
induce FREE RADICAL formation which causes breaks in DNA strands
bleomycin USE
testicular cancer
Hodgkin lymphoma
bleomycin TOX
PULMONARY FIBROSIS
skin changes (flagellate skin discoloration)
minimal myelosuppression
etoposide (VP-16) and teniposide MOA
inhibit topoisomerase II to increase DNA degrad
etoposide (VP-16) and teniposide USE
small cell carcinoma of lung
prostate cancer
testicular carcinoma
etoposide (VP-16) and teniposide TOX
myelosuppression
GI irritation
alopecia
alkylating agents
cyclophosphamide, ifosfamide
nitrosureas
busulfan
cyclophosphamide, ifosfamide MOA
covalently X-link (inter strand) DNA at guanine N-7
requires bioactivation by liver (P450)
cyclophosphamide, ifosfamide USE
non-Hodgkin lymphoma
breast, ovarian carcinoma
immunosuppressants
cyclophosphamide, ifosfamide TOX
myelosuppression
HEMORRHAGIC CYSTITIS
what partially prevents cyclophosphamide, ifosfamide tox?
mesna - thiol group binds toxic metabolite, acrolein
nitrosureas
carmustine
lomustine
semustine
streptozocin
nitrosurea MOA
require bioactivation.
can cross BBB into CNS.
nitrosurea USE
BRAIN TUMOR including glioblastoma multiforme
nitrosurea TOX
CNS toxicity - dizziness, ataxia
busulfan MOA
alkylates DNA
busulfan USE
CML
also used to ablate BM before BM transplant
busulfan TOX
PULMONARY FIBROSIS
hyperpigmentation
which chemo drug can cross BBB and thus, treat brain tumor?
nitrosureas
microtubule inhibitors
vincristine, vinblastine
paclitaxel, other taxols
vincristine, vinblastine MOA
alkaloids that bind beta-tubulin in M-PHASE and block polymerization of microtubules so mitotic spindle cannot form
vincristine, vinblastine USE
Hodgkin lymphoma
Wilms tumor
choriocarcinoma
ALL
vincristine TOX
NEUROTOXICITY - areflexia, peripheral neuritis
paralytic ileus.
myelosuppression.
paclitaxel, other taxols MOA
hyperstabilize polymerized microtubules in M-PHASE so that mitotic spindle cannot break down and ANAPHASE CANNOT OCCUR
paclitaxel, other taxols USE
breast, ovarian carcinomas
paclitaxel, other taxols TOX
myelosuppression.
hypersensitivity.
cisplatin, carboplatin MOA
contains platinum.
cross-links DNA.
cisplatin, carboplatin USE
testicular, bladder, ovary, lung carcinomas
cisplatin, carboplatin TOX
NEPHROTOXICITY AND ACOUSTIC NERVE DAMAGE
how can platinum drug nephrotoxicity be prevented?
amifostine - free radical scavenger
PLUS chloride diuresis
hydroxyurea MOA
inhibit ribonucleotide reductase - decrease DNA synthesis (S PHASE)
hydroxyurea USE
melanoma
CML
sickle cell disease (increase HbF)
hydroxyurea TOX
myelosuppression.
GI upset.
prednisone MOA
trigger apoptosis.
may even work on nondividing cells.
prednisone USE
CLL
Hodgkin lymphoma*
immunosuppressant for AI d/o
*part of MOPP regimen
prednisone TOX
Cushing-like syndrome immunosuppression cataracts acne osteoporosis HTN peptic ulcers hyperglycemia psychosis
tamoxifen, raloxifene MOA
SERMs - block binding of estrogen to ER+ cells.
receptor antagonists in BREAST, agonists in BONE.
tamoxifen, raloxifene USE
breast cancer
*also useful for preventing osteoporosis
tamoxifen TOX
may increase risk of endometrial carcinoma via partial agonist effects. also cause hot flashes.
raloxifene TOX
NO INCREASE in endometrial carcinoma bc it is an endometrial antagonist
trastuzumab (Herceptin) MOA
monoclonal Ab against HER2 (erb B2), a tyrosine kinase
helps kill breast cancer cells that overexpress HER2, possibly through Ab-dependent cytotoxicity
trastuzumab USE
metastatic breast cancer
trastuzumab TOX
cardiotoxicity
imatinib (Gleevec) MOA
inhibit Ph chromo bcr-abl tyrosine kinase
imatinib USE
CML
GI stromal tumors
imatinib TOX
fluid retention
rituximab MOA
monoclonal Ab against CD20 on most B cell neoplasms
rituximab USE
non-Hodgkin lymphoma rheumatoid arthritis (plus MTX)
ondansetron
inhibits serotonin (5HT-3) receptors. treat nausea and vomiting due to chemo.
*receptors are located in presyn terminals of vagus nerve and also centrally in chemoreceptor trigger zone and solitary nucleus/tract
