Male Urogenital Pharm - Fitz Flashcards
Describe hormones in the H-P-Testes axis and what they do (GnRH, FSH, LH, T, E, DHT)
- GnRH –> FSH and LH (pulsatile)
- LH –> Leydig cells –> testosterone production (pulsatile)
- FSH + Testosterone –> Sertoli cells –> Sperm
- Aromatase (sertoli cells) converts some testosterone to estradiol
- 5-alpha reductase (leydig cells) convert some testosterone to DHT
What enzyme is required to turn Androstenedione into Testosterone OR Estradiol?
17-beta hydroxylase
Feedback inhibition of H-P-T axis
Testosterone (androgens) AND Estradiol both cause inhibition at hypothalamus and pituitary
Molecular indicator of potential prostate cancer
Prostate cancer grading system
PSA level
Gleason Scale (1-10)
First line therapy for slowing/stopping the growth of prostate cancer
Androgen deprivation
3 GnRH-related drugs used for fertility issues /prostate cancer
Gonadorelin (natural GnRH)
Leuprolide (agonist)
Degarelix (antagonist)
After administering Leuprolide, what will you see?
Why does this happen?
Initial surge of FSH, LH, and testosterone, followed eventually by down-regulation of the GnRH receptor and decreased hormone levels
Not PULSATILE like it normally is
What are other potential issues w/ Leuprolide/testosterone that must also be managed?
Adrenals OR tumor cells may make their own testosterone, thus not allowing for sufficient androgen deprivation
How are the Leuprolide testosterone surge and other testosterone productions managed?
Names?
Molecular result?
Androgen receptor antagonists
Bicalutamide
Flutamide
No dimerization, transport, or transcription by androgen receptor
Abiraterone - MoA
Used for what?
What else is important? Why?
Inhibits 17-alpha hydroxylase AND 17, 20-lyase (CYP17), thus preventing testosterone production
Androgen deprivation in prostate tumor cells
Must be given w/ PREDNISONE or other corticoids – CORTISOL production is also inhibited and ALDOSTERONE accumulates
How is Ketoconazole different than Abiraterone?
Difference in findings/side effects?
Ketoconazole – also blocks pregnenolone production from cholesterol
NO aldosterone accumulation
When is Ketoconazole used?
With what else?
Side effect?
Men with advanced prostate cancer that need prompt drops in testosterone levels
Corticosteroid (cortisol replacement)
HEPATOTOXICITY
What is Finasteride? What is it used for? Can it be used for prostate cancer?
- 5-alpha reductase inhibitor
- BPH
- NO – may increase growth of the cancer (according to studies)
A male patient has a low sperm count, and LH/FSH levels are low. Cause?
Want to stimulate spermatogenesis in the short term. Tx?
Issue with this?
Better way to Tx?
2º hypogonadism – Exogenous steroids not taken in pulsatile way
Beta-hCG = acts like LH but w/ longer 1/2 life
Testosterone will still cause negative feedback on the system
Clomiphene (ER antagonist) or Anastrozole (aromatase inhibitor) –> cause loss of negative feedback by estradiol –> causing increased GnRH
