Anti-cancer Drugs Flashcards
How does methotrexate work
it’s an antimetabolite - inhibits dihydrofolate reductase, which inhibits the conversion of dUMP to dTMP, which decreases DNA and decreases protein synthesis
What are the 3 uses for methotrexate
- Solid cancer: leukemia, lymphoma, sarcomas, choriocarcinoma 2. Abortion, ectopic pregnancy 3. Immunosuppression: rheumatoid arthritis, psoriasis
Methotrexate toxicity
myleosuppresion that is reversible with folinic acid “rescue” (Leucovorin) and fibrotic lung
Mechanism of 5 flourouracil
a pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid - this inhibits thymidylate synthase, which decreases dTMP, which decreases DNA and protein synthesis
5FU has synergy with
Methotrexate
How is 5FU myelosuppression different from MTX
Myelosuppression is not reversible with leucocorin in 5-FU, but is with MTX. neeed thymidine rescue with 5-FU
What is the mechanism of 6-Mercaptopurine (6-MP)
A purine analogue (just like allopurinol) that decrease de novo synthesis. Activated by HGPRTase.
What is the toxicity of 6-MP increased with
It’s metabolized by xanthine oxidase, so toxicity increases with allopurinol
What is 6-Thioguanate (6-TG)
The same as 6-MP except it can be given with allopurinol
Cytarabine
A pyrimidine analog - inhibition of DNA polymerase
All anti metabolites work in
S phase
Dactinomyocin
Intercalates DNA
Dactinomyocin is used for
Children’s tumors: wilm’s tumor, ewing’ sarcoma, rhabdomyosarcoma
How does doxorubicin work
It generates free radicals by noncovalently (dactinomyocin covalently) intercalating DNA, causing breaks in DNA, which decreases replication
Doxorubicin toxicity and Rx for that
cardiotoxicity - because the heart lack superoxide dismutase, causing cardiomyopapthy; Dexrazoxane is used to prevent it
Bleomycin MOA
Induces free radical formation, which causes breaks in DNA strands
Eradicated Ball Cancer
Etoposide, Bleomycin, Cisplatin
Bleomycin toxicity
Pulmonary fibrosis
Etoposide (VP16) MOA
Inhibits topoisomerase 2, causing increased DNA degradataion - forms a complex between topoisomerase and 2 and DNA
Which antibiotics work like etoposide
Flouroquinolones
Etoposide is used for
Small cell carcinoma of the lung and prostate, testicular cancer
This drug alkylates DNA and causes pulmonary fiborsis
Busulfan
This drug fragments DNA and causes pulmonary fibrosis
Bleomycin
This drug blocks purine synthesis, and is metabolized by xanthine oxidase
6-mercaptopurine: antimetabolite
This drug cross links DNA and is neprho and oto toxic
Cisplatin, carboplatin, oxaliplatin
Nitrogen mustard that alkylates DNA (electrophile that binds DNA)
Cyclophosphamide (DMARD)
Folic acid analog that inhibits dihydrofolate reductase
Methotrexate
Prevent tubulin dissasembly
Paclitaxel and other taxols P
Pyrimidine analog that is bio-activated to 5F-dUMP, which covalently complexes folic acid. This complex inhibits thymidylate synthase, which decreases dTMP and decreases DNA and protein synthesis
5-FU
Intercalates DNA, produces free oxygen radicals, and cardiotoxic
Doxorubicin
DNA alkylating agent used in brain cancer
Nitrosureas cross blood brain bar
Prevents Tubulin assembly
Vincristine and vinblastine
Inhibits thymidylate synthase - leading to decrease nucleotide synthesis
5-FU
SERM - blocking estrogen binding receptors
Tamoxifen, raloxifene: antagonist in breat and agonist in bone. tamoxifen may increase the risk of endometrial carcinoma via partial agonist effects - raloxifen is an endometrial antagonists
Mechanism similar to antiviral acyclovir and foscarnet
Cytarabine (pyrimidine analog = inhibition of DNA polymerase)
Mechanisms similar to flouroquionlones
Etoposide
mechanisms similar to trimethoprim
methotrexate (folic acid analog that inhibits dihydrofolate reductase = dec dTMP = dec DNA = dec. protein synthesis
monoclonal antibody against HER2 (erb-2)
Trastuzumab
Free radical induced DNA strand breakage
Bleomycin, Doxorubicin, Daunorubicin
Inhibitor of PRPP synthetase
6-MP: purine thiol analog = dec de novo purine synthesis, activated by HGPRtase
Reversible with Leucovorin
Methotrexate
Treatment for choriocarcinoma
Methotrexate, vinblastine, vincristine
Treatment for AML
Cytarabine
Treatment to CLL
Busulfan, Imatinib
Prevents breast cancer
tamoxifen and raloxifene
Treatment for testicular cancer
“Eradicate Ball Cancer”
- Etoposide
- Bleomycin
- Cisplatin
Applied topically for AKs and basal cell cancers
5-FU
Treatment for childhood tumors (ewing sarcoma, wilms tumor, rhabdomyosarcoma)
Dactinomcyin
Inhibits ribonucleotide reductase
Hydroxyurea: dec DNA synthesis ( s phase specific)
Side effect of hemorrhagic cystitis
Acrolein produced by cyclophophamide
Antibody against Philadelphia chromsome
Imatinib
Side Effects of prednisone
Immunosuppression - osteoporosis - acne - catarcts - cushingoid features - peptic ulcers - hypertension -hyperglycemia - insomnia - psychosis