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Flashcards in Male Urogenital Pharm - Fitz Deck (14):
1

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

2

What enzyme is required to turn Androstenedione into Testosterone OR Estradiol?

17-beta hydroxylase

3

Feedback inhibition of H-P-T axis

Testosterone (androgens) AND Estradiol both cause inhibition at hypothalamus and pituitary

4

Molecular indicator of potential prostate cancer

Prostate cancer grading system

PSA level

Gleason Scale (1-10)

5

First line therapy for slowing/stopping the growth of prostate cancer

Androgen deprivation

6

3 GnRH-related drugs used for fertility issues /prostate cancer

Gonadorelin (natural GnRH)
Leuprolide (agonist)
Degarelix (antagonist)

7

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

8

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

9

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

10

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

11

How is Ketoconazole different than Abiraterone?


Difference in findings/side effects?

Ketoconazole -- also blocks pregnenolone production from cholesterol

NO aldosterone accumulation

12

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

13

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)

14

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