signal transduction Flashcards
What is LHRH and what can it also be called?
Luteinizing hormone releasing hormone
- which can be called gonadotropin releasing hormone
what are some LHRH analogs?
Leuprolide
Goserelin
What are 8 ways to decrease testosterone?
- Remove Testicles (1940s)
- Remove Testicles and Adrenals (1960s)
- Remove Pituitary Gland (1970s)
- Use LHRH Antagonist (2008)
- Use LHRH Super-agonist (1985)
- Use LH Antagonist (not yet)
- Use an inhibitor of steroid biosynthesis (1960s)
- Use a neutralizing antibody (not yet)
What is a LHRH super-angonist?
- material that binds to LHRH receptor
- increases LH and testosterone initially then falls to castrated levels
- nearly no side effects
What is the MOA of Leuoprolide?
Signal transduction inhibitor
Receptor super-agonist
- peptide
What does Leuoprolide mainly fight against?
Prostate and breast cancers
What are some side effects of Leuprolide and Goserelin?
osteoporosis
worsening insulin resistance
What is dagarelix?
It is a GnRH antagonist
- cause castrate levels of testosterone in 24hrs
What are 17a-hydrozyprogesterone and Abiraterone?
They are Lyase inhibitors that act to decrease the amounts of androgens oestrogens
- the second has a 20% Increase in survival after 1 year
- The later must be given with Adrenocorticoids****
What are ways to decrease growth promoting signals and hormones in the body?
- Remove hormone producing organ
- Lower conc. of hormone in the blood
- Block the ability for hormone to interact with its receptor
- block the down-stream signaling between the receptor and effector apparatus
How do we block testosterone?
Block conversion of T to DHT
Block androgen receptor
What converts Testosterone to DHT?
5-alpha reductase
What is Enzalutamide and what its MOA?
Potently shuts down AR signaling
- receptor antagonists
- fights against prostate cancer
What does aromatase produce and from what?
Estradiol from Testoterone
Estrone from androstenedione
What are some inhibitors of aromatase and estrogen lowering drugs?
Anastrozole and exemestane
What is the MOA of Anastrozole and what is it used for?
signal transduction inhibitor and ligand reduction
- fights against breast cancer
What are the side effects of Anastrozole?
Arthralgia and myalgia
Exemestane- those plus suicide substrate of hormone
What is Tamoxifen?
Selective Estrogen Receptor Modulator (SERM)
- fights against breast cancer
- Receptor antagonist but there are different isoforms of the estrogen receptor and this doenst act against all
What is fulvestrant?
ER antagonist which outperforms Tamoxifen
What is Endoxifen?
metabolite of Tamoxifen which is 100x more potent
- made via CYP3A4/5 and CYP2D6
