Flashcards in Renal 2 Pharmacology 2 Deck (48)
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1
Male Hypothalamic-Pituitary-Gonadal Axis
-release/secretion of hypothalamic and anterior pituitary hormone is pulsatile
-GnRH in hypothalamus stimulates pituitary to Release FSH and LH which stimulates sertoli cells and leydig cells
2
Anterior pituitary LH stimulates
Leydig cells testosterone biosynthesis and secretion
3
Testosterone + pituitary FSH stimulates
sertoli cells-->sperm maturation
4
Sperm maturation in Sertoli cells
-depends on FSH and testosterone, but also on precisely controlled estrogen levels
-Aromatase in sertoli cells uses testosterone to make estradiol
5
GnRH (LHRH)
-released by hypothalamus
-stimulates anterior pituitary to produce and secrete FSH and LH
6
FSH
-released by anterior pituitary
-stimulates sertoli cells and sperm maturation
7
LH
-released by anterior pituitary
-stimulates testosterone hormone synthesis and secretion by leydig cells
8
Continual high concentrations of LH result in
reduced secretion of testosterone due to down regulation of LH receptors in Leydig cells
9
Androgens, testosterone
-released by adrenals and testes
-stimulates Sertoli cells (other cells responsive to androgens, e.g. prostate epithelium)
10
Estrogens, estradiol
-released by adrenals and testes
-formed by aromatase catalyzed conversions of androgens to estrogens
11
Aromatase
-converts androstenedione to estrone and testosterone to estradiol
12
Synthesis of dihydrotestosterone
-androstenedione converted to testosterone by 17B-hydroxylase
-testosterone converted to DHT by 5a-reductase
13
Synthesis of estradiol in males
-estrone converted to estradiol by 17B-hydroxylase or testosterone converted to estradiol by aromatase
14
High concentrations of testosterone in the circulation
-inhibit the release of GnRH, FSH, and LH, by negative feedback control
15
When circulating concentrations of testosterone are low,
-higher levels of GNRH, FSH, and LH are released
16
Testicular levels of testosterone are
100-500x greater than those found in blood
17
An in crease in PSA level over time may indicate
prostate cancer
18
Androgens stimulate
prostate cancer cells to grow
-lowering androgen levels or stopping androgens from signaling in prostate cancer cells often makes tumors shrink or grow more slowly for a time.
-Androgen deprivation therapy alone does not cure prostate cancer
19
GnRH antagonist
Degarelix
20
GnRH agonist
Leuprolide
-Nafarelin (nasal)
21
Natural replacement of GnRH
Gonadorelin
22
Degarelix
-GnRH antagonist (blocks receptor on pituitary)
-reduces testosterone levels below detectable levels quickly (2-3 days)
-used to treat advanced prostate cancer
-given subcutaneously as a monthly injection
-counters reflex to try to produce more T because receptor is blocked
23
Degarelix Side effects
-problems at injection site (pain, redness, swelling) and increased levels of liver enzymes on lab tests
24
Continuous administration fo a GnRH agonist (Leuprolide)
-eventually desensitizes receptors for GnRH and LH after an initial 'surge' in androgen biosynthesis
25
Leuprolide
-causes circulating testosterone to surge initially, then drop later due to desensitization of GnRH and LH receptors
-cause testicles to shrink over time (chemical castration)
-other GnRH agonists include goserelin, triptorelin, and histrelin
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How to manage testosterone flare that coincides with administration of GnRH receptor agonists
-concurrent administration of androgen receptor antagonists
27
Androgen receptor antagonists include
Bicalutamide
Flutamide
Nilutamide
28
Bicalutamide
-used with leuprolide or other GnRH agonists
-favored
-1x a day
29
Flutamide
used with GnRH/LHRH agonists
30
