HPA - bk Flashcards
GH receptor
jak stat
Criteria for dx of GH deficiency
growth rate of < 4 cm per year
no GH in serum despite bein g given to secretagogyes
Name the recombiant Growth Hormone(s)
Somatropin - recombiant GH
Somatrem - GH analogue
~*Effects of somatropin and somatrem in GH deficient adults
improved metabolic state
increased lean body mass
sense of well being
~* Effects of somatropin and somatrem in HIV positive patients
increased lean body mass and weigh and physical endurance
Use of somatropin and somatrem in short bowel syndrome
improved GI function when receiving specialized nutritional support
A/se of somatropin and somatrem
generally well tolerated BUT
- scoliosis (due to rapid growth)
- hypothyroidism
- intracranail hypertension - rare
- otitis media (increased risk at turners)
- pancreatitis
- gynecomastia
- nevus growth
- diabetic syndrome (opposes insulin) at chronic used
A/se of GH in adults
peripheral odema myalgia arthralgia @ hand and wrists carpal tunnel syndrome proliferative retinopathy **ie think acromegaly symtpoms
Mecasermin = ?
recombinant IGF-1 analog and recombinant IGF-binding protein 3
use of Mecasermin?
children wtih growth faiure that have an IGF-1 deficiency (due to mutations in GH receptor and development of neutralizing Gh abs)
A/se mecasermin
** opposite of what you would think = hypglycemia
intracranial hypertension
asymptomatic elevation fo lvier enzymes
How to treat Gh secreting adenomas please
Gh receptor antagonists
Somatostatin analogs
DA receptor agonists
What is pegvisomant?
GH receptor antagonist
Ocreotide =
somatostatin
Ocreotide MOA
inhibits release of GH, TSH, glucagon, insulin and gastrin
Advantage of Ocreotide acetate over ocretoide alone-zees
long acting suspension that you can give at 4 week itnervals
~*~Use of Ocreotide
1) reduce symptoms caused by all the lil hormone secreting tumours (acro, carcinoid, gastrinoma etc)
2) localizing neuroendocrine tumours
3) acute control of esophageal varices ****
SHARK: provide acute control for bleeding from esophageal varices
ocreotide!!!
A/se for DOC @ gastrinoma
n/v, ab cramps, flatulence, steatorrhea constipation biliary sludge and gallstones sinus bradycardia and conduction disturbaces vitamin B 12 deficiency@ long term use
Name some DA agonists:
bromocriptine (shark flash back - parkinsons)
cabergoline
Treat a pit adenoma that is secreting a bunch a prolactin
bromocriptine or cabergoline DA agonists (inhibi of prolactin @ pti)
Uses of Bromocriptine/cabergoline
hyperprolatinemia
acromegaly (alone or with surgery, radiation, ocreotide)
A/se bromocriptine/cabergoline
nausea (worse with B over C), h/a light headedness, orthostatic hypotension, fatigue
psych manifestations
high dose = cold induced peripheral digital vasosapsm
pulmonary infiltirares - chronic high doages terapy **repeat from parkinson lecture = pulmoanry infiltrates with ergot derviatives
Name the analogs of FSH and LH
menotropins - FSH and LH
follitropin - recombinant FSH
urofollitropin - purified human FSH extract
Name the human chorionic gonadotropin extract and where we get it from
choriogonadotropin = recominant
how do you give choriogonadotropin?
SC or IM
Receptor of gonadotropins please :)
GPCRs
CLinical application of gonadotropins
1) ovluation induction
2) male infertility (FSH and LH required; can give choriogonadotropin alone or with urofollitropin, rFHS and rLH)
A/se of gonadotropins in a) women and b) men
WOMEN - ovarion hyperstimulation syndrome + multiple pregnancies (ie mom getting jerm and jerm <3), headache, depression, oedema, precocious pubery
MEN - gyneCOmastiaaa
Name the Gonadotropin releasing hormone analgos
gonadorelin - GnRH
goserelin - GNRH analog
leuprolide - GnRH analog
nafarelin - GnRH analog
If I say goserelin, you think?
leuprolide and nafarelin
GNRH analogs
Describe the differences in the effects of PULSATILE and SUSTAINED NONPULSATILE administration of GnRH (gonadorelin, goserelin, leuprolide, nafarelin)
pulsatlie - stimulats release of LH and FSH ie jsut liek real physiology time
sustained non pulsatile - inhibits FSh and LH –> hypogonadism
Advantage of goserlin/leuprolide and nafenlin vrs gonadorelin
analogs (goserelin, leuprolide and nafenelin) are more potent and longer lasting than gonadarelin
Describe the PK of the gonadtropin releasing hormone and analogs
gonadorelin - IV or Sc
analongs (goserelin ,leuprolide, naferelin) –> SC, IM , nasal (naferlin), Sc implant NOT IV!!! makes sense bc of long t1/2 - wont be used in emergent sitautions
If I give a patient a continuous administartion of gonadorelin what would I expect to see?
a BIPHASIC response
a) first 7 days get a reponse flare
b) chronic effects - inhibitory (downregulation and changes in signalling pathways)
Clinical applications of the GNRh and analogues
1) Female infertility - UNCOMMON
2) Male infertility - with hypothalamic hypogonagotropic hypogonadism @ pulsatile gonadorelin
3) diagnosis of LH responsiveness - differentiates between pubtery due to constitutional delay of hypogonadotropic hypogonadism
~*~ DOC @ controlled ovarian hyperstimulation (SHARK: side effect of mentropins/follitropin and urofollitropin)
Leuprolide and nafarelin (GnRh analgoues) (same treatment as prostate cancer - no nafarelin)
~*~ DOC @ endometriosis
leuprolide, goserelin, nafarelin - pain decreased due to cyclical changes of e and p stopped.
~*~ DOC @ uterine leiomyomata
leuprolide, goserelin, nafarelin
~*~ DOC @ prostate cancer
leuprolide, goserelin ( ovariona hyperstimulation same meds, no nafarelin)
Other uses of suppresion by GnRH analogs: times four
a) central precocious puberty with leuprolide and nafarelin (opp prostate cancer and ovarian hyperstimulation - leuprolie and goserelin)
b) advanced breast and ovarian cancer
c) treatmetn of amenorrhoea and infertilty in women wtih PCOD
d) thinning of endometrial lining
A/se Gonadorelin
h/a, lightheadedness, n, glusing
swelling at injection site
generalized hypersensitivity dermatitis @ long term administration
rate acute hypersensitivy reactions
**sudden pituitary apoplexy and blindness
Name the GNRH receptor ANTAGONISTS
Cetrorelix
Ganirelix
COMPETITVE antags of GnRh receptors
Cxl app for cetrorelix and ganirelix
suppression of gonadotropin production - prevent LH surge @ controled ovarian hyperstimulation
Name the adrenocorticotropic hormone analogs
corticotropin
cosyntropin
ACTH analogs
I say MC2R, you think?
a GPCR = icnreased cAMP
Uhoh. Im not sure if the patient has primary adrenal insufficiency/addisons disease or secondary adrenal insufficiency/not enough ACTH around, what do i do?
give em an adrenocorticotropic hormone analog ie coticotropin or cosyntropin hurrah! one day for real!!
Effects of small vrs higher doses of oxytocin
1) small dose - increases force and frequency of contractions
2) higher dose - evokes sustained contractions and weak ADH and aldoseterone activitin
3) milk ejection
Uses of oxytocin
IV – initation and augmentation of labour
IM – used to control postpartum bleeding
Control the uterine hemorrhage!!!
oxytocin. bamalam
Control the esophageal varice bleeding!
ocreotide!
A/se oxytocin
1) excessive uterin contractions
2) inadvertent activation of vasopressin receptors
3) bolus causing HYPOTENSION (opposite of what you’d think from the whole mimicks vasopression/ADH weak activity thing, hurrayy!)
What is Atosiban?
oxytocin antagonist
Uses of atosiban
preterm labout, jk. not in the US.. canada?
Name the ADH agonists
vasopression
desmopressin
MOA and kinetic-y things of Desmopressin please
long acting minimal V1 (vasoconstrictive) effects antidiuretic : pressin activity - 4000x
DOC @ diabetes insipiduse
vasopression
desmopression
uses for vasopression
esophageal variceal bleeding (with ocreotide), colonic diverticular bleeding ** vasoconstriction
uses for demsopressin
coagulopathy treatment in hemophilia A and vWF disease
Name a vasopressin antagonist and its love for what receptors
conivaptan loves V1 AND V2.
DOC @ hemophilia A and vWf
desmopressin
DOC @ colonic diverticular bleeding
vasopressin
`DOC @ patients with hypnatremia due to elevated vasopression
conivaptan
