signal transduction

Question 1

What is LHRH and what can it also be called?

Answer 1

Luteinizing hormone releasing hormone

- which can be called gonadotropin releasing hormone

Question 2

what are some LHRH analogs?

Answer 2

Leuprolide

Goserelin

Question 3

What are 8 ways to decrease testosterone?

Answer 3

1. Remove Testicles (1940s)
2. Remove Testicles and Adrenals (1960s)
3. Remove Pituitary Gland (1970s)
4. Use LHRH Antagonist (2008)
5. Use LHRH Super-agonist (1985)
6. Use LH Antagonist (not yet)
7. Use an inhibitor of steroid biosynthesis (1960s)
8. Use a neutralizing antibody (not yet)

Question 4

What is a LHRH super-angonist?

Answer 4

• material that binds to LHRH receptor
• increases LH and testosterone initially then falls to castrated levels
• nearly no side effects

Question 5

What is the MOA of Leuoprolide?

Answer 5

Signal transduction inhibitor
Receptor super-agonist
- peptide

Question 6

What does Leuoprolide mainly fight against?

Answer 6

Prostate and breast cancers

Question 7

What are some side effects of Leuprolide and Goserelin?

Answer 7

osteoporosis

worsening insulin resistance

Question 8

What is dagarelix?

Answer 8

It is a GnRH antagonist

- cause castrate levels of testosterone in 24hrs

Question 9

What are 17a-hydrozyprogesterone and Abiraterone?

Answer 9

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****

Question 10

What are ways to decrease growth promoting signals and hormones in the body?

Answer 10

1. Remove hormone producing organ
2. Lower conc. of hormone in the blood
3. Block the ability for hormone to interact with its receptor
4. block the down-stream signaling between the receptor and effector apparatus

Question 11

How do we block testosterone?

Answer 11

Block conversion of T to DHT

Block androgen receptor

Question 12

What converts Testosterone to DHT?

Answer 12

5-alpha reductase

Question 13

What is Enzalutamide and what its MOA?

Answer 13

Potently shuts down AR signaling

• receptor antagonists
• fights against prostate cancer

Question 14

What does aromatase produce and from what?

Answer 14

Estradiol from Testoterone

Estrone from androstenedione

Question 15

What are some inhibitors of aromatase and estrogen lowering drugs?

Answer 15

Anastrozole and exemestane

Question 16

What is the MOA of Anastrozole and what is it used for?

Answer 16

signal transduction inhibitor and ligand reduction

- fights against breast cancer

Question 17

What are the side effects of Anastrozole?

Answer 17

Arthralgia and myalgia

Exemestane- those plus suicide substrate of hormone

Question 18

What is Tamoxifen?

Answer 18

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

Question 19

What is fulvestrant?

Answer 19

ER antagonist which outperforms Tamoxifen

Question 20

What is Endoxifen?

Answer 20

metabolite of Tamoxifen which is 100x more potent

- made via CYP3A4/5 and CYP2D6