Androgen agents Flashcards
where is testosterone synthesized? from what molecule?
leydig cells
cholesterol
what enzymes is responsible for converting androsteonedione to testosterone?
17B-hydroxysteroid dehydrogenase (17B-HSD)
17B-hydroxysteroid dehydrogenase (17B-HSD) is responsible for what conversion?
androsteonedione to testosterone
is albumin bound testosterone considered bioavailable or not bioavailable?
bioavailable
primary hypogonadism is due to what cause? what is the result? what are the testosterone, GnRH / LH / FSH levels?
testicular dysfunction leading to decrease in testosterone production
loss of negative feedback - decrease in testosterone does not inhibit GnRH, LH, FSH
testosterone - low
GnRH / LH / FSH - high
secondary hypogonadism is due to what cause? what is the result? what are the testosterone and LH / FSH levels?
hypothalamus / pituitary - decrease in circulating gonadotropins
decrease in circulating gonadotropins
testosterone - low
LH / FSH - low
what is the route for methyltestosterone? what type of testosterone derivative is it?
oral, sublingual
17 alkylated
what is the route for testosterone enanthate? what type of testosterone derivative is it?
IM
testosterone ester
what is the route for testosterone?
transdermal or topical
how are the pharmacokinetics of testosterone esters different from testosterone?
increased lipophilicity
IM
slow release, slower metabolism
longer duration
how are the pharmacokinetics of 17-alkylated derivatives different from testosterone?
slower catabolism
oral route
liver toxicity and hepatic cancer
what are the antiandrogen classes?
androgen receptor antagonists
GnRH agonists
GnRH antagonists
steroid synthesis inhibitors
flutamide and bicalutamide are what class of drug? what is their MOA?
non steroidal anti-androgens
competitive inhibitor of androgen binding to AR
flutamide and bicalutamide are used for what condition/
prostate cancer
what class of drug is enzalutamide? what is the MOA?
androgen receptor antagonists
competitive inhibitor of androgen binding to AR
what are the additional effects of enzalutamide?
inhibits nuclear translocation of AR
blocks DNA binding
blocks coactivator recruitment
what class of drug are leuprolide and goserelin? what are they used for?
GnRH agonists
prostate cancer
what is the result of leuprolide and goserelin administration?
initially increases LH and testosterone production
over time, leads to desensitization and downregulation of GnRH receptors on pituitary gonadotropes (pulsatile vs continuous) - DECREASE IN TESTOSTERONE LEVELS
what are the adverse effects of GnRH agonists?
sexual dysfunction bone mineral density loss anemia fatigue initial surge in testosterone levels that can cause growth of prostate cancer
what must be used to prevent the initial testosterone surge prior to leuprolide / goserelin treatment that can increase cancer growth? what is the rationale for this?
an AR receptor antagonist (flutamide)
preventing the EFFECT of the testosterone surge (but not the surge itself)
what class of drug is degarelix?
GnRH receptor antagonist
what makes degarelix different from GnRH agonists?
faster onset
no LH (testosterone) surge
reduce LH / FSH production and release
decrease testosterone production - more effective
what class of drug is abiraterone? what is it used for? which drug is it combined with?
androgen biosynthesic inhibitor
metastatic prostate cancer
prednisone
how can abiraterone cause HTN, hypokalemia, and fluid retention?
intermediates from 17a-HSD inhibition are shunted into aldosterone pathway - increased mineralcorticoids (aldosterone)
what class of drug are finasteride and dutasteride? what are they used for?
5a-reductase inhibitors
BPH
what is thought to be the causative agent of androgenic alopecia?
DHT (increased levels)
what is used to treat male pattern baldness?
finasteride (Propecia)
what are the adverse effects of 5a-reductase inhibitors?
lower PSA levels (false negatives for prostate cancer)
impotence, gynecomastia
ED drugs inhibit what enzyme? what is the result?
PDE-5
increase cGMP in smooth muscle - continued relaxation
what are the PDE5 inhibitors?
sildenafil (Viagra)
vardenafil (Levitra)
tadalafil (Cialis)
how are PDE5 inhibitors metabolized?
metabolized primarily by cyp450 enzymes
what are the adverse effects of the PDE5 inhibitors?
dangerously low BP in patients taking nitrates / nitrites
priapism
sudden vision loss
what are the androgenic functions of androgens in the male?
maturation and continued function of male reproductive tract and production of secondary male sexual characteristics
androgens have metabolic functions in which areas of the male body?
muscle, bone, bone marrow, liver
which molecule stimulates the production of testosterone by Leydig cells?
LH
what is the function of 5a reductase?
converts testosterone to DHT
which is more potent - DHT or testosterone?
DHT
what is a significant adverse effect of the 17-alkylated testosterone derivatives?
carcinoma
what is the general MOA of the GnRH agonists and GnRH antagonists?
reduce secretion of LH (thus reducing testosterone)
what drugs are given before administration of GnRH analog treatment? why?
flutamide and bicalutamide
prevent effects of initial testosterone surge via LH
what is the MOA of abiraterone?
blocks 17a-hydroxylase
what is a side effect of inhibiting 17a-hydroxylase?
adrenal insufficiency (loss of glucocorticoid production)
which compounds cause an initial surge in testosterone production? which drugs need to be included to prevent this?
GnRH agonists
AR antagonists
