Male Urogenital Disorders Pharm

Question 1

GnRH/LHRH-receptor AGONISTS. Halt testosterone synthesis from where?

Answer 1

Leuprolide. Halt testosterone synthesis from testicles.

Question 2

GnRH/LHRH-receptor ANTAGONIST. Halt testosterone synthesis from where? Used to tx?

Answer 2

Degarelix. Used for tx advanced prostate.

Halt testosterone synthesis from testicles.

Question 3

Degarelix admin

Answer 3

s.q./mo

Question 4

Describe degarelix effect on circulating testosterone.

Answer 4

Promptly drop after injection of GnRH ANTAGONIST within 1 day –> below threshold by post-tx day 4.

Question 5

Describe leuprolide effect on circulating testosterone.

Answer 5

• Initial effect is stimulation - “testosterone surge” until day 7 after admin.
• Continuous exposure - GnRH-receptor desensitization and then androgen deprivation.

Question 6

What causes testicles to shrink over time?

Answer 6

GnRH agonists - leuprolide

Question 7

A man has bone pain and paralysis after taking drug for prostate cancer. What drug is he taking and what does it mean about his cancer?

Answer 7

Taking GnRH agonist - leuprolide.
-Cancer has met to his bones (spine) - “t-surge” caused short term tumor growth in spine can compress spinal cord and cause pain/paralysis.

Question 8

Name the three locations of testosterone synthesis

Answer 8

Testicles > adrenals, prostate

Question 9

ORAL anti-androgens used to concomitantly with leuprolide to combat “t-surge”.

Answer 9

Bicalutamide** (qd), Flutamide (tid)

Question 10

ORAL anti-androgen used to concomitantly with surgical castration..

Answer 10

Nilutamide

Question 11

Three palliative effects of anti-androgens for met prostate cancer.

Answer 11

• Reduced bone pain
• Better performance status
• Increased sense of well being.

Question 12

What drug nullifies testosterone production in prostate tumor cells used in conjunction with GnRH ant/agonist?

Answer 12

Abiraterone.

Question 13

MOA of abiraterone.

Answer 13

1. inhibit 17alpha-hydroxylase –> stops conversion fo pregnenolone and progesterone to derivatives.
2. cut C17,20 lyase (CYP17) –> halting DHEA and androstenedione formation –> no DHT

Question 14

What MUST be used/added to abiraterone regimen? Why?

Answer 14

CS or prednisone because of cortisol deprivation.

Question 15

Two main SE of abiraterone

Answer 15

1. Cortisol deprivation

2. Aldosterone accumulation (fluid retention, Na+ retention)

Question 16

What drug, similar in effects to abiraterone - in ald accum/cortisol deprevation - often requires discontinuation and why?

Answer 16

Ketoconazole. Bc of hepatotoxicity

Question 17

Two Steroid Alpha Reductase inhibitors that relieve BPhypertrophy

Answer 17

Finasteride and dutasteride

Question 18

Enzyme selectivity of Finasteride v. Dutasteride.

Answer 18

• FIasteride = speciFIc inhibitor (SAR2)

- DUtasteride = DUal inhibitor (SAR1 and 2)

Question 19

Indirect and direct consequences of SAR2 inhibition

Answer 19

• Direct - DHT depetion

- Indirect - AR receptor less occupied –> no gene transcription

Question 20

Why shouldn’t finasteride be used for prostate cancer prevention?

Answer 20

Because fewer tumors, but 22% more were highly malignant.

Question 21

If anabolic steroids are used, what is messed up in hypothalamus-pit-test axis?

Answer 21

Pulsatile release of GnRH, resulting in severe hypogonadism and infertility by suppressing HPG axis - (low E, low T)

Question 22

In the setting of secondary severe hypogonadism and infertility due to anabolic steroids, what drugs can have important uses in recovering testosterone production?

Answer 22

SERMs - clomiphene

Aromatase inhibitors - anastrazoel and letrazole

Question 23

MOA of Clomiphene (SERM) -

Answer 23

MOA: estradiol antagonist.
It ‘tricks’ the hypothalamus to “conclude” that estrogen levels are low, stimulating hypothalamus to produce
LHRH. This will act to increase LH and restart natural testosterone production.