Male Urogenital Pharm-Fitzpatrick

Question 1

Testosterone plus pituitary FSH stimulates ___ cells

Answer 1

Sertoli –> sperm maturation

Question 2

Anterior pituitary LH stimulates __ cells

Answer 2

Leydig –> testosterone biosynthesis

Question 3

This enzyme in sertoli cells uses testosterone to make estradiol

Answer 3

Aromatase

Question 4

Leydig cells convert testosterone to DHT by this enzyme

Answer 4

Steroid 5 a reductase

Question 5

Continual high concentrations of __ result in reduced secretion of T due to downregulation of their receptors in leydig cells

Answer 5

LH

Pulsatile discharge of LH is important to create concentrations of T essential for spermatogenesis

Question 6

__ stimulates sertoli cells to convert T to estradiol and other estrogens. Sertoli cells convert T to Estradiol utilizing their __ enzyme

Analagous to T, estrogens in the blood act on the hypothalamus and exert a negative feedback on GnRH, in turn, ___ are reduced

Answer 6

FSH

Aromatase

LH and FSH

Question 7

List a GnRH antagonist

Answer 7

Degarelix

Question 8

List a GnRH agonist

Answer 8

Leuprolide

Question 9

___ is a GnRH/LHRH antagonist that reduces that reduces T levels below detectable levels quickly. It is used to tx advanced prostate cancer, given subq as a monthly injection and common side effects include pain and redness at injx site and increased levels of liver enzymes on lab tests

Answer 9

Degarelix

Question 10

Describe circulating T levels after Degarelix administration

Answer 10

Graphically, circulating T levels drop PROMPTYL after injection of a GnRH antagonist

Question 11

Describe the initial effect and the continuous exposure with Leuprolide administration

Answer 11

Initial effect: stimulation – > initial androgen surge

Continuous exposure: receptor desensitization and eventual downregulation

Question 12

___ causes circulating T to surge initially, then drop later due to sensitization of GnRH and LH receptors

Answer 12

Leuprolide-GnRH agonist

Question 13

___ cause testicles to shrink over time

Answer 13

Leuprolide and related GnRH agonists

Question 14

GnRH agonists cause testosterone levels to surge briefly before falling to very low levels. Men whose cancer has metastasized to the bones may have bone pain. If the cancer has spread to the spine, even a short-term increase in tumor growth as a result of the flare could compress the SC and cause pain or paralysis. Flare can be avoided by concomitant administration of ___ for a few weeks when starting tx with leuprolide or related GnRH agonists

Answer 14

Anti-androgens

Question 15

List some androgen receptor antagonists

Answer 15

Bicalutamide (used with Leuprolide)
Flutamide
Nilutamide (used in combo with surgical castration)

Not often used in the US

Question 16

These drugs compete with T and DHT for receptor–> No AR dimerization, No AR transport, No transcription

Answer 16

AR antagonists

Question 17

What is the prototype now of anti-androgens?

Answer 17

Bicalutamide

Flutamide was the prototype

Question 18

List drugs that target disruption of androgen biosynthesis

Answer 18

Abiraterone

Ketoconazole

Question 19

___ blocks CYP17 to lower tumor production of androgens. It is approved for advanced prostate cancer

Answer 19

Abiraterone

Question 20

What enzyme is inhibited by Abiraterone?

Answer 20

CYP17

This includes 17a hydroxylase, 17,20 lyase

Beneficial effect: androgen deprivation in prostate tumor cells

Question 21

What are side effects of Abiraterone?

Answer 21

Cortisol deprivation –> Always given with prednisone or cortisol replacement therapy

Aldosterone accumulation –> give aldosterone receptor antagonist

Question 22

___ in high doses blocks production of androgens. Used to treat men recently diagnosed with advanced prostate cancer by lowering T levels prompty. It also blocks the production of cortisol, thus, pts treated with this drug need to take a corticosteroid to prevent side effects due to low cortisol levels

Answer 22

Ketoconazole

Question 23

Ketoconazole has significant __ toxicity often requiring its discontinuation

Answer 23

Hepato

Question 24

What is a risk of treating prostate cancer with BPH drugs?

Answer 24

Increased risk of high grade prostate cancer with 5-AR inhibitors finasteride and dutasteride

Question 25

___ has the biologic activity of LH but a longer half-life in the circulation. It stimulates the Leydig cells to synthesize and secrete testosterone. It is used in men who have secondary hypogonadism and desire to become fertile

Answer 25

HCG

It has an alpha subunit identical to FSH and LH

Question 26

Secondary hypogonadism can be due to:

Answer 26

Exogenous androgens

Anabolic steroids including androstenedione, testosterone overexposure

Not pulsatile…you get potential distortion of estrogen synthesis

Question 27

___ is a SERM used for enhanced recovery of T production after anabolic steroid cycles

Answer 27

Clomiphene

Question 28

___ tricks the hypothalamus to “conclude” that estrogen levels are low

Answer 28

Clomiphene

Question 29

Release of hypothalamic and AP hormone is ___

Answer 29

Pulsatile