Male Urogenital Pharm-Fitzpatrick Flashcards
Testosterone plus pituitary FSH stimulates ___ cells
Sertoli –> sperm maturation
Anterior pituitary LH stimulates __ cells
Leydig –> testosterone biosynthesis
This enzyme in sertoli cells uses testosterone to make estradiol
Aromatase
Leydig cells convert testosterone to DHT by this enzyme
Steroid 5 a reductase
Continual high concentrations of __ result in reduced secretion of T due to downregulation of their receptors in leydig cells
LH
Pulsatile discharge of LH is important to create concentrations of T essential for spermatogenesis
__ 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
FSH
Aromatase
LH and FSH
List a GnRH antagonist
Degarelix
List a GnRH agonist
Leuprolide
___ 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
Degarelix
Describe circulating T levels after Degarelix administration
Graphically, circulating T levels drop PROMPTYL after injection of a GnRH antagonist
Describe the initial effect and the continuous exposure with Leuprolide administration
Initial effect: stimulation – > initial androgen surge
Continuous exposure: receptor desensitization and eventual downregulation
___ causes circulating T to surge initially, then drop later due to sensitization of GnRH and LH receptors
Leuprolide-GnRH agonist
___ cause testicles to shrink over time
Leuprolide and related GnRH agonists
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
Anti-androgens
List some androgen receptor antagonists
Bicalutamide (used with Leuprolide)
Flutamide
Nilutamide (used in combo with surgical castration)
Not often used in the US
These drugs compete with T and DHT for receptor–> No AR dimerization, No AR transport, No transcription
AR antagonists
What is the prototype now of anti-androgens?
Bicalutamide
Flutamide was the prototype
List drugs that target disruption of androgen biosynthesis
Abiraterone
Ketoconazole
___ blocks CYP17 to lower tumor production of androgens. It is approved for advanced prostate cancer
Abiraterone
What enzyme is inhibited by Abiraterone?
CYP17
This includes 17a hydroxylase, 17,20 lyase
Beneficial effect: androgen deprivation in prostate tumor cells
What are side effects of Abiraterone?
Cortisol deprivation –> Always given with prednisone or cortisol replacement therapy
Aldosterone accumulation –> give aldosterone receptor antagonist
___ 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
Ketoconazole
Ketoconazole has significant __ toxicity often requiring its discontinuation
Hepato
What is a risk of treating prostate cancer with BPH drugs?
Increased risk of high grade prostate cancer with 5-AR inhibitors finasteride and dutasteride
___ 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
HCG
It has an alpha subunit identical to FSH and LH
Secondary hypogonadism can be due to:
Exogenous androgens
Anabolic steroids including androstenedione, testosterone overexposure
Not pulsatile…you get potential distortion of estrogen synthesis
___ is a SERM used for enhanced recovery of T production after anabolic steroid cycles
Clomiphene
___ tricks the hypothalamus to “conclude” that estrogen levels are low
Clomiphene
Release of hypothalamic and AP hormone is ___
Pulsatile
