194b RE pharm 1 - male Flashcards
GnRH
small peptide - pulse every 2 hours in males
G prtn –> PLC –> Ca –> secretion of FSH/LH
continuous GnRH desensitized pituitary - superagonists (leuprolide)
classes of GnRH drugs
gonadorelin - synthetic GnRH; must be pulsatile for stimulatory effect
leuprolide - superagonist GnRH (decreases LH/FSH); depot forms for 1-3 months
Cetrorelix - GnRH antagonist (decreases LH/FSH); daily
**all peptides so need IV/SC
gonadorelin uses
diagnostic to distinghuish b/w pituitary failure and hypothalamus (inject gonadorelin and measure LH)
Rx hypothalamic hypogondatropic hypogonadism
leuprolide use
precocious puberty
metastatic PC
adverse effects of leiprolide and cetrorelix
ED
Initial flare –> BPH/bone pain (use antagonists)
headache, pituitary dysfunction, hypersensitivty
gonadotropins
FSH, LH, hCG
glycoproteins w/ a and b subunits (a common, b specific)
gonads – GPCR –> cAMP
FSH –> spermatogensis + androgen BP
LH –> testosterone synthesis
**some cross over b/w FSH and LH
gonadotropins use
dx delayed puberty (inject hCG and measure testorone) - gonad vs hypo/pit
induces spermatogensis if hypogonadotropic hypogonadism (can cause gynecomastia)
androgen
major from testes is testerone
adnrenal - DHEA
ovaries - testorone
mech andrgoen
steroids - intracellular receptors - homodimers - interact with transcactivating factors - mRNA production
androgen actions - male
fetal:
internal ducts of male tract
male genitlaia development
puberty (pit less sensitive to inhibition)
GnRH vastly increases androgen (~50x)
changes growth, hair, genitals, acne
adult:
maintenance of 2nd sex char (libido, prostate, seminal vesicles)
spermatogenesis
anabolic - muscle but limited b/c receptor mediated; high amounts can block cortisol (which are catabolic so thus produces anabolic affect)
growth plate maturation
erthropoetin production - increases RBCs
androgen feedback
inhibin –I FSH
testorone –I LH and GnRH
androgen orally effective?
no - rapidly metabolizerd by liver so need parenteral
androgen activation at target
converted to DHT by 5 a reducatase in repro tract and hair follcles
other tissue converted to estriadiol in CNS, liver, adipose, bone
testerone agents + SE
testosterone propionate - depot prep for sustained
methyltesterone - synethic, oral
stanozolol - anabolic steroid, oral; androgen-receptor independent effects; cause infertility in high dose (feedback inhibition)
decreases HDL, increase LDL, acne, prostate tumor
androgen use
replacement therapy
anabolic in premature infants, post op, anemia
palliative actions –I estrogen (breast cancer)
rx for hereditary angionuerotic edema –I capillary leakage
