antihormonal Flashcards
hydroxy urea and mechanism of action on ribonucleotides
The primary site of action of Hydroxyurea is the enzyme ribonucleoside diphosphate reductase which catalyzes the coversion of ribonucleotide to deoxyribonucleotides, a rate limiting step in the synthesis of DNA.
The drug specifically target S phase of cell cycle in which the concentration of this reductase enzyme is maximum.
By binding to this enzyme, hydroxyurea causes cells to arrest at G1 to S interface.
use and toxicity hydroxy urea
The specific use is in myelo-proliferative syndrome, chronic granulocytic leukemia, polycythemia vera and thrombocytosis.
Also be effective in sickle cell disease.
Hydroxyurea may also potentiate anti-proliferative effects of DNA damaging agents such as cisplatin, alkylating agents or topoisomerase-II inhibitors.
Toxicities: hematopoitic depression- leukopenia, megaloblastic anemia, teratogenic
l asparaginase mechanism of action
Normal tissues synthesize L-asparagine amino acid in the presence of asparagine synthetase in sufficient amount for protein synthesis.
Neoplastic cells are unable to synthesize this amino acid due to lack of asparagine synthetase enzyme.
These cells take asparagine from plasma/circulation.
use and toxicity l asparaginase
L-asparaginase anticancer drug deprives neoplastic cells of asparagine by inhibiting asparagine synthetase enzyme and convert this into aspartic acid and ammonia.
This drug in combination with methotrexate/doxorubicin/vincristine and prednisolone for the treatment of acute lymphoblastic leukemia and other high grade lymphomas.
Resistance against this drug can be developed through induction of asparagine synthetase in tumors cells.
Toxicities include: hypersensitivity, hyperglycemia, hypertriglyceridemia, pancreatitis.
tamoxifen
Tamoxifen is a competitive inhibitor of estradiol binding to the estrogen receptor (ER).
After binding to the ER, tamoxifen induces a change in the three dimentional shape of the receptor, inhibiting its binding to the estrogen responsive element on DNA.
mechanism of action
Under normal physiological condition, estrogen stimulation increases tumor cell production of transforming growth factor β (TGF-β).
By blocking these pathways, the net effect of tamoxifen treatment is to decrease the autocrine stimulation of breast cancer growth.
Tamoxifen also decreases the local production of insulin-like growth factor-1 by surrounding tissues. It is a growth factor for cancer cells.
use and toxicity
Tamoxifen is extremely useful for the treatment of breast cancer.
Also be effective in progesterone-resistant endometrial cancer.
Slow the development of osteoporosis.
Decrease the risk of myocardial infarction.
Toxicities:
menstrual irregularities, nausea and vomiting,
vaginal bleeding
SAA
. Steroidal anti-androgen(SAA) -Cyproterone acetate, Megestrol acetate
SAA are weak partial agonists and competitive inhibitors of the androgen receptor in target tissues.
ADRs: They cause loss of libido, decreased sexual potency and low testosterone level.
NSSA
NSAA inhibit translocation of the androgen receptor to the nucleus from the cytoplasm of target cells and induce anti-proliferating effect in prostate cancer.
Flutamide was the first androgen receptor antagonist. It is metabolized into alpha-hydroxyl flutamide (more potent than parent drug).
Side effects include diarrhea, emesis, reversible liver abnormalities.
