Anterior Pituitary Drugs Flashcards
GH/IGF-1 promotes
lipolysis, glycogenolysis, detents against hypoglycemia
Laron’s Dwarfism
mutations in GH receptor - completely resistant to GH but respond to IGF-1
GH>GHR>JAK2 kinase>STAT5>IGF-1
GH release inhibited by
somatostatin, glucose load, FA’s, B-adrenergics
Stim. by sleep, protein, a-adrenergics, exercise
Provocative testing for GH
stimulate GH with arginine, clonidine, or insulin (hypoglycemia); oral glucose load should suppress GH
Somatotropin
recombinant hGH to treat GH deficiency (Turner’s, chronic renal disease)
- C/I: any active malignancy, ICU
- S/E: HA, HTN, increased cranial P, arthralgias, carpal tunnel
- SQ injection
Mecasermin
IGF-1 therapy, SQ injection
- For GH deficiency, Laron’s dwarfism, STAT56 mutations
- C/I: active neoplasm, hypoglycemia conditions
Octreotide
Somatostatin analog inhibits GH secretion; SQ
- Treats acromegaly, decreases portal HTN, inhibits insulin release
- S/E: gallstones or gallbladder sludge
Pegvisomant
GH receptor antagonist, SQ, PEGylated
- Treat acromegaly not responding to other drug/surgery
- S/E: hepatitis, tumor growth (can get adenoma)
- IGF-1 used to assess dosing, not GH
Bromocriptine, Cabergoline
Dopamine agonists - stimulate GH secretion but can inhibit it in adenomas of mixed somatotropes/lactotropes (GH/PRL)
PRL regulation
- mainly inhibition through dopamine
- stimulated by estrogen, breast manipulation, high TRH
Hyperprolactinemia causes
amenorrhea, galactorrhea, ED, libido loss
- caused by pituitary adenoma, D2 antagonists, polycystic ovarian syndrome, primary hypothyroidism (TRH hormone spillover)*
Treat PRL excess with
Bromocriptine, Carbegoline (higher affinity, better tolerated)
- S/E: GI complaints, orthostasis, syncope
Gonadotropins
FSH, LH, hCG (placenta) - all have same alpha unit; Beta unit confers specificity (LH and hCG similar and activate LH receptor)
- activate GPCRs>AC>cAMP
FSH
- Sertoli cells/granulosa cells
> spermatogenesis, inhibin secretion/supports follicle growth and estrogen synthesis
LH
Leydig cells/Theca cells, CL
- promotes testosterone synthesis/estrogen and progesterone
hCG
- corpus luteum
- stimulates progesterone production
Inhibin
increased by FSH; feeds back to suppress gonadotropes and inhibit FSH secretion
GnRH stimulates
FSH/LH release; very pulsatile
- receptors down-regulated if constant delivery of GnRH
- Inhibited by testosterone, estrogen, progesterone
Follicular Phase
Gonadotropins stimulate follicle growth and estrogen - stimulates endometrium
Ovulation
Estrogen increases and does positive feedback on gonadotropes and causes LH surge > ovulation
- residual follicle becomes corp. luteum producing estrogen and progesterone
Luteal phase
increasing progesterone stimulates endometrium to vascularize and secrete mucus
- feedback to pituitary increases amplitude and longer frequency of gonadotropin pulses
Menstruation
If unfertilized, CL regresses, endometrium no longer supported
Fertilization
trophoblast synth. hCG - supports estro/prog. synthesis by CL until week 9 when placenta takes over
Cryptorchidism
failure of testes descent - requires hCG
