Cancer drugs Flashcards
Methotrexate- mechanism
dihydrofolate reductase inhibitor
Methotrexate- uses
Cancer- ALL, AML, breast cancer
Uterine pathology- ectopic pregnancy, abortion, choriocarcinoma, hydatiform mole
Immunosuppression: RA, psoriasis
Methotrexate- toxicity
bone marrow suppression- reversible with leucovorin (folin acid analog)
pulmonic fibrosis (methotrexate lung)
hepatotoxicity
5-Fluorouracil-mechanism
pyrimidine analog bioactivated to 5F-dUMP, which complexes covalently with folic acid. This complex inhibits thymidylate synthase, which then inhibits DNA synthesis.
5FU uses
colon cancer
topical use for actinic keratosis
pancreatic cancer
basal cell carcinoma
5FU side effects
Myelosuppression, not reversible with leucovorin
Uridine is a possible rescue agent
photosensitivity
Azathioprine, which is bioactivated to 6MP
MOA
purine analog, inhibits PRPP imidotransferase
6MP (azathioprine) uses
prevents organ rejection, RA, IBD, SLE
use to wean patients off steroids in chronic disease
use to treat steroid- refractory chronic disease
6MP (azathioprine) toxicity
myelosuppression
hepatotoxicity
increased toxicity with allopurinol or febuxostat which are also metabolized by xanthine oxidase enzyme
6TG is metabolized by a different enzyme, so it can be combined with azathioprine
cyclophosphamide/ ifosfamide MOA
bioactivated by the liver, then acts as an alkylating agent, cross- links DNA at guanine N7
cyclophosphamide uses
cancer: solid tumors, leukemia, lymphomas
immunosuppresant: lupus nephritis, polyarteritis nodosa
ifosfamide uses
testicular cancer. Ifosfamide is not used for testicular cancer
cyclofosfamide/ifosfamide toxicity
both drugs can lead to myelosuppression.
These alkylating agents form a toxic metabolic Acrolein, which can induce hepatotoxicity. For this reason, administer cyclofosfamide/ifosfamide with Mesna, which binds the Acrolein up and makes cyclophosphamide/ifosfamide safer
Both drugs are also associated with increased rates of transitional cell bladder cancer
Nitrosoureas: MOA
bioactivated alkylating agent that cross- links DNA in the CNS
Nitrosoureas- uses
brain tumors (including glioblastoma multiforme)
nitrosoureas- toxicity
CNS toxicity (convulsions, dizziness, ataxia)
Busulfan- MOA, uses, toxicity
alkylating agent that cross- links DNA
used for CML, ablation of bone marrow before bone marrow transplantation
toxicity: PULMONARY FIBROSIS
hyperpigmentation
Doxorubicin, daunorubicin: MOA, uses, toxicity
What drug is used to prevent toxicity?
- intercalates into DNA so that it can’t unwind
- generates free radicals
used to treat lymphoma, leukemia, solid tumors
toxicity: cardiotoxicity (dilated cardiomyopathy)
myelosuppression
alopecia
note: heart muscle relatively deficient in SOD
Dexrazoxane is an iron chelating agent that is used to prevent cardiotoxicity
Dactinomycin
intercalates DNA, used for children's tumors -Wilm's tumor -Ewing sarcoma -Rhabdomyosarcoma
generates free radicals and intercalates DNA
Daunorubicin/doxorubicin
inhibits dihydrofolate reductase
Methotrexate
inhibits thymidylate synthase
5-FU
inhibits PRPP amidotransferase
6MP
inhibits DNA polymerase
Cytarabine (pyrimidine analog)
Give dexrazoxane with … for…
dexrazoxan with daunorubicin/doxorubicin
for cardiotocity
Give leucovorin with … for…
leucovorin with methotrexate for myelosuppression rescue
give mesna with… for…
cyclophosphamide and ifosfamide for toxic acrolein metabolite, which causes hemorrhagic cystitis
give uridine with… for…
uridine is a rescue agent for 5FU myelosuppression
Bleomycin
generates free radicals leading to DNA damage.
use for testicular cancer (along with etoposide and cisplatin), Hodgkin lymphoma
toxicity: pulmonary fibrosis
lance can’t take bleomycin because he races
pulmonary fibrosis
methotrexate (antimetabolite) lung
busulfan alkylating agent
bleomycin antitumor antibiotic
folic acid analog that inhbits dihydrofolate reductase
methotrexate
pyrimidine analog that inhibits thymidylate synthase
5-FU
how does the body metabolize 6MP?
xanthine oxidase
which cancer drug is often used in rheumatoid diseases and ectopic pregnancy?
methotrexate
alkylates DNA, toxicity includes pulmonary fibrosis
Busulfan
fragments DNA, toxicity includes pulmonary fibrosis
bleomycin
blocks purine synthesis, metabolized by xanthine oxidase
azathioprine (6MP)
nitrogen mustard, alkylates DNA
nitrosoureas
folic acid analog that inhibits dihydrofolate reductase
methotrexate
intercalates DNA, produces oxygen free radicals, cardiotoxic
doxorubicin, daunorubicin
DNA alkylating agents used in brain cancer
nitrosoureas
applied topically for actinic keratoses and basal cell cancers
topical 5FU
treatment for childhood tumors (Ewing sarcoma, Wilms tumor, rhabdomyosarcoma)
dactinomycin
side effect of hemorrhagic cystitis
cyclophosphamide and ifosfamide
cisplatin, carboplatin, oxaliplatin
cross-link DNA
GU treatments include ovarian cancer, bladder, cancer, testicular cancer, lung carcinoma
toxicity includes nephrotoxicity, ototoxicity
prevent nephrotoxicity with amifostine (free radical scavenger), and
chloride (saline) diuresis
Etoposide, teniposide
etoposide inhibits topoismerase II, enhancing DNA degradation by super-coiling
use for solid tumors (particularly testicular and small cell lung cancer), prostate cancer
leukemias, lymphomas
toxicity includes myelosuppression
testicular cancer regimen
Eradicate Ball Cancer
etoposide, bleomycin (or ifosfamide), cisplatin
irinotecan and topotecan
these inhibit topoisomerase I
irinotecan is used for metastatic colon cancer
topotecan is used for small cell lung cancer, ovarian cancer, cervical cancer
Vincristine
blocks polymerization of microtubules
used to treat hodgkin lymphoma, Wilms tumor, Ewing sarcoma, choriocarcinoma
side effects:
neurotoxicity
peripheral neuritis
Vinblastine
blocks mictotubule polymerization
indications are also similar to vincristine
WT, choriocarcinoma, Ewing sarcoma, Hodgkin lymphoma
toxicity:
myelosuppression
Vinblastine blasts bone marrow
Paclitaxel
hyperstabilizes polymerized microtubules in M phase, so that mitotic spindle cannot break down (anaphase cannot occur)
used for ovarian and breast carcinomas
toxicity: hypersensitivity
drugs that work on microtubules
vincristine vinblastine paclitaxel mebendazole albendazole griseofulvin colchicine
hydroxyurea
inhibits ribonucleotide reductase, thereby inhibiting DNA synthesis (S-phase specific)
used for melanoma, CML, sickle cell disease (increased HbF)
toxicity: severe myelosuppression, GI upset
Prednisone
triggers apoptosis in lymphoid tumors like CLL and Hodgkin lymphoma
BAM CUSHINGOID
buffalo hump
amenorrhea
moon facies
crazy ulcers skin changes htn infection necrotic femoral head glaucoma osteoporosis immunosuppression diabetes
Selective estrogen receptor modulators (SERMs)
Tamoxifen
ER antagonist at breast
ER agonist in bone
ER partial agonist in endometrium
use for ER+ breast cancer
prevent cancer in patients with BRCA mutation
tox: increased risk of endometrial carcinoma via overstimulation of endometrial tissue
in women with endometrial cancer, tamoxifen can be used for treatment
Raloxifene SERM
used to treat osteoporosis
ER antagonist
- breast
-endometrium
ER agonist
-bone
Trastuxumab
monoclonal antibody against HER2 receptor (TKR), which helps to kill cancers that overexpress HER2.
Useful only for HER-2+ breast cancer and gastric cancer (tras2zumab)
Cardiotoxicity- HER2 Heartceptin hurts the heart
inhibits microtubule formation
vincristine
inhibits microtubule disassembly
paclitaxel
inhibits ribunucleutide reductase
hydroxyurea
inhibits topoisomerase II
etoposide
inhibits topoisomerase I
topotecan
Cardiotoxicity
trastuzumab (herceptin)
hypersensitivity reactions
paclitaxel
increased risk of endometrial cancer
tamoxifen
nephrotoxicity and ototoxicity
cisplatin
peripheral neuropathy
vincristine
Rituximab
antibody against CD20 used for lymphomas, leukemias RA vasculitis pemphigus vulgaris ITP
tox: increases risk of progressive multifiocal leukencephalopathy
Bevacizumab
monoclonal antibody against VEGF, inhibits angiogenesis
cancers need new blood vessels or they will die
treat metastatic colon cancer
metastatic cervical cancer
certain types of lung cancer
metastatic renal cell carcinoma
side effects: impaired wound healing, severe hemorrhage (hemoptysis, GI bleeding, epistaxis)
Imatinib
enzyme inhibitor
targets BCR-Abl TKR, produced by t(9;22) Philadelphia chromosome
CML
ALL
AML
cross-links DNA, nephrotoxic, ototoxic
cisplatin
carboplatin
oxaliplatin
prevents tubulin disassm
Paclitaxel
inhibits ribonucleotide reductase
hydroxyurea
inhibitor of the mutated tyrosine kinase produced by the Philadelphia chromozome
imatinib
monoclonal antibody against HER2
trastuzumab
SERM that does not increase the risk of endometrial cancer
raloxifene
