Hypothalamic/Pituitary Hormones Flashcards
what receptors are activated by growth hormone
JAK/STAT superfamily
what receptors are activated by prolactin
JAK/STAT
what receptors are activated by TSH
GPCR
what receptors are activated by FSH
GPCR
what receptors are activated by LH
GPCR
what receptors are activated by ACTH
GPCR
what is the primary target of GHRH?
Growth hormone –> IGF-1 (mediates most of response)
acts on liver, muscle, bone, kidney
**notably also acts on some insulin receptors - causing insulin like effects
what are the effects of GH on GFR, insulin and adipocytes?
increase GFR
anti-insulin: decrease glucose utilization, inc lipolysis - receptors become unresponsive with long term use of GH d/t overproduction of insulin – NIDDM like state
stimulate pre-adipocyte differentiation into adipocytes
somatropin vs somatrem?
somatropin = recombinant GH
somatrem = GH analog
use of recombinant GH
peds patients with:
- GH deficient
- chronic renal failure
- Noonan syndrome
- Prader Wili
- Turner
- idiopathic short stature
GH deficient in adults
Wasting in HIV pt
Short bowel syndrome
Recombinant GH AE
scoliosis during rapid growth
- hypothyroidism
- intracranial HTN - fatal AE (can increase CSF production)
- otitis media - in Turner pt
- pancreatitis, gynecomastia, nevus growth
- diabetic syndrome with chronic use
Adult AE:
- peripheral edema, myalgias, carpal tunnel syndrome
- peripheral retinopathy
Recombinant GH contraindication
p450 inducer
pt with malignancy = may increase growth of tumor
Mecasermin
IGF-1 analog
recombinant IGF-1 and human IGF-binding protein 3
Mecasermin use
mutated GH-R, neutralizing GH antibodies
mecasermin AE
hypoglycemia - eat before/after to counter AE
intracranial HTN
elevated liver enzymes
treatment for GH secreting tumors
seen as acromegaly or gigantism (if occurs in childhood)
1) GH-r antagonist
2) somatostatin analog
3) dopamine-r agonist
Pegvisomant
GH-r antagonist
prevent dimerization of receptor - still allows for receptor binding
ocreotide
somatostatin analog
ocreotide MOA
inhibits release of GH, TSH, glucagon, insulin, gastrin
- more potent than somatostatin**
ocreotide AE
n/v cramps, steatorrhea
constipation
biliary sludge/gallstones
bradycardia
B12 deficiency - w/long term use
pain at injection site
bromocriptine
dopamine agonist
cabergoline
dopamine agonist
use of bromocriptine/cabergoline
adenomas that secrete excess prolactin
*oral/vaginal insert
bromocriptine/cabergoine use
hyperprolactinemia
acromegaly
bromocriptine/cabergoline aE
nausea, headache, lightheadedness, orthostatic hypotension
(bromocriptine»cabergoline)
psych manifestations
high dose - cold induced peripheral vasospasms
pulmonary infiltrates with high dosage
use of gonadotrophins
infertility – stimulate spermatogenesis or induce ovulation
menotropins
hMG = purified extract of FSH and LH
follitropin
recombinant FSH
urofollitropin
uFSH = purified human FSH extract
choriogonadotropin alpha
(rhCG) recombinant hCG given SC
gonadotropin MOA
act through GPCRs
tx male infertility
FSH and LH both required if hypogonadal
hCG alone
urofollitropin, rFSH, rLH
AE gonadotropins
ovarian hyperstimulation
multiple pregnancies
headache, depression, precocious puberty
male – gynecomastia
gonadorelin
gonadotropin releasing hormone synthetic
goserelin
GnRH analog - (more potent than gonadorelin)
leuprolide
GnRH analog(more potent than gonadorelin)
nafarelin
GnRH analog(more potent than gonadorelin)
pulsatile vs sustained nonpulsatile administration of GnRH analogs
pulsatile = required to stimulate LH and FSH release
nonpulsatile = inhibits FSH and LH release – leads to hypogonadism
GnRH analog use
suppression =
controlled ovarian hyperstimulation - suppress endogenous LH surge
endometriosis = reducing exposure to cyclical changes in estrogen and progesterone
uterine fibroids
prostate cancer
precocious puberty
adv breast/ovarian cancer
tx amenorrhea, PCOD
thinning of endometrial lining (pre-op endometrial ablation)
stimulation =
female/male infertility
diagnosis of LH responsiveness
gonadorelin AE
hypersensitivity
pituitary apoplexiy and blindness
headache, light headed ness
GnRH analog AE
menopausal sxs
depression
diminshed libido
vaginal dyrness
contraindicated in pregnant and breast feeding women
men: hot flushes, sweats, gyenocmastia, decreased hematocrit
cetrorelix
competitive antagonist of GnRH receptors
ganirelix
competitive antagonist of GnRH receptor
GnRH receptor antagonist use
suppress gonadotropin production = prevent LH surge during controleld ovarian hyperstimulation
corticotropin
ACTH analog
cosyntropin
ACTH analog
ACTH analog MOA
act via MC2r (inc cAMP) stimulate adrenal cortex = release glucocorticoids and androgen precursors
ACTH released from pituitary in pulses - highest in am, lowest in pm
cortisol suppresses release
ACTH use
differentiate between primary and secondary insufficiency
infantile spasm/West Syndrome treatment
ACTH AE
glucocorticoids
Oxytocin low dose vs high dose
low dose: increases force, frequency of contractions
high dose: sustained contractions, weak antidiuretic and pressor activity
contraction of myoepithelial cells surrounding mammary alveoli = milk ejection
oxytocin IV vs IM use
IV: intitiation and augmentation of labor
IM: post partum bleeding
oxytocin clinical application
1) labor induction
2) augment normal labor
3) control uterine hemorrhage
oxytocin AE
excessive uterine contraction stimulation
activation of vasopressin receptors
if bolus administration = hypotension
oxytocin contraindications
fetal distress, premature
abnormal fetal presentation
uterine rupture predisposition
atosiban
oxytocin antagonist
atosiban use
pre-term labor = not used in US
Vasopressin
ADH agonist
Desmopressin
ADH agonist
long acting synthetic analog of vasopression
minimal V1 activity
Vasopressin PD/PK
2 receptos activated
V1R = vascular SM = vasoconstriction V2R = renal tubule cells = inc water permeability, water reabsorption
shorter t 1/2 with vasopressin rather than desmopressin
Vasopressin use
diabetes insipidis
esophagal varice bleeding
colonic diverticular bleeding
desmopressin use
coagulapathy in hemophilia A and vWB disease
vasopressin AE
overdosage = hyponatremia, seizures
conivaptan
vasopressin antagonist
used in pt with hyponatremia d/t elevated vasopressin
high affinity for V1, V2
