Kruse DSA: Hypothalamic and Pituitary Hormones Flashcards
GH
somatropin
IGF-1
Mecasermin
Somatostanin analogs
- Octreotide
- Lanreotide
GH antagonists
Pegvisomant
Dopamnine agonists
- bromocriptine
- cabergoline
Vasopressin receptor agonists
Vasopressin
Desmopressin
Vasopressin receptor antagonists
- cconivaptan
- Tolvaptan
What kind of hormones are from the ant pit?
-peptide hormones
What provides the blood flwo to the ant pit
-the portal venous system that drains the hypothalamus
What negatively regulates the ant pit?
- somatostatin
- dopamine
- both from hypothalamus
the posterior pituitary is an extension of neurons from the hypothalamus…. from what 2 nuclei do they originate in?
- Supraoptic: Vasopressin
- paraventricular: Oxytocin
What do GH and PRL activate?
- JAK/STAT kinase linked receptors
- they are single-chain protein hormones
What ant pit hormones activate GPCRs?
- TSH
- FSH
- LH
- they are dimeric ptns
What ant pit hormone is a single peptide that is cleaved froma larger precursor containg the peptide B-endorphin?
ACTH
-it also binds GPCRS
What feeds back and inhibits TSH and TRH?
-T3 and 4
What feeds back to inhibit FSH, LH, and GnRH?
- estrogen and progesterone in women
- androgens in men
What inhibits ACTH and CRH
cortisol
Growth hormone
- stimulated by GHRH
- inhibited by SST
- GH and IGF feed back to inhibiti GH release
Prolactin
- inhibited via the D2 dopamine receptors (Gi)
- so, disruption of pitutary stalk and hypothalamohypophysial portal vessels will increase PRL levels while the other hormones will decrease***
What is weird about GnRH?
- When released in pulses, stimulates LH and FSH release
- when administered continuously, it inhibits LH and FSH release
What does ACTH target (organ)
Adrenal gland
What is GH metabolized by?
- liver
- CYP450
What receptor does GH get?
Jak/STAT
-IFG-1 production
What do we give ppl who have a GH deficiency?
rhGH
GH toxicity and contraindications
- well tolerated in children
- adults: peripheral edema, myalgias, arthralgia, carpal tunnel syndrome
- contraindicated in patients with a known malignancy
Mecasermin
- when children are unresponsive to exogenous GH, use this
- it’s a complex of recombinant human IGF-1 and IGFBP-3 (that incrases the half-life of rhIGF-1)
- subcue
What is the most common adverse effect of Mecasermin?
- hypoglycemia
- so eat 20 minutes before and you’ll be good to go
What are GH antagonists use for?
- ant pit adenomas that secret GH
- remember, acromegaly in adults, gigantism in children
Somatostatin analogs
- inhibits GH, glucagon, insulin ,and gastrin release
- exogenous SST has a really short half life
- found in hypothalamus, pancrease, and GI tract
What are the longer acting SST analogs?
- octreotide
- Lanreotide
Which drug is approved for the treatment of acrogmegaly?
-Lanreotide
Adverse effects of SST analogs
- GI: diarrhea, nausea, ab pain
- Gallbladder sludge and gallstones.. because decreased gallbladder contraction and bile secretion
- Cardiac effects (sinus bradycardia, conduction disturbances), Vitamin B12 deficiency
What is Pegcisomant?
- GH receptor antagonist
- a PEG derivative of a mutant GH that binds to GH receptor and allows receptor to dimerize, but does not activate the JAK-STAT signaling cascade or stimulate IGF-1 secretion
- used to treat acromegaly as well
Prolactin
- lactation
- no preparations are available for use in PRL-deficient patients
- if they have hyperprolactinemia, just give them a dopamine agonist
How does hyperprolactinemia present in women and men?
- Women: amenorrhea and galactorrhea
- Men: decreased libido and headaches)
How is inhibition of PRL secretion achieved?
by use of dopamine agonists
-dopamine= Prolactin inhibiting factor (PIF)
What are the 2 dopamine agonists?
- Bromocriptine
- Cabergoline
What else can dopamine agonists be use for?
-to shrink a prolactin-secreting tumor
Toxicity and contraindications of dopamine agonists
- nausea, headache, light-headedness, orthostatic hypotension, fatigue are most common
- psych… takes months to resolve
- pts with macroadenomas and preggo continue therapy
- pts w. microadenomas and preggo discontinue therapy b/c microadenoma growth during pregnancy is rare
- not recommended to suppress postpartum lactation due to increased indcidence of stroke or coronary thrombosis
Oxytocin
- stimulates uterine contraction and elicits milk ejection in lactating women
- administered IV for initiation and augmentation of labor and IM for control of postpartum bleeding
- this is a post pit thing remember
Vasopressin (ADH)
Desmopressing
long acting synthetic analog of casopressin with minimal Va receptor activity
-mainly a good antidiuretic
What receptors does vasopressin get?
- GPCR’s V1 receptors found on vascular smooth muscle… vasoconsriction
- V2 receptors found on renal tubule cells… increases water permeability in collecting tubules
What else will activation of the V2 receptor do?
release factor VIII and VWF
What do we use vaso and desmopressin for?
- diabetes insipidus (the central kind)
- remember, that’s the test to see if it’s central or nephrogenic…. if desmopressin makes it better
Which one has higher V2 receptor affinity?
desmopressin
What else could desmopressin be used for since it activates those V2 receptors?
-Hemophilia A (factor VIII deficiency) and VWD
Toxicity and contraindications for vaso/desmopressin?
- headache, nausea, ab cramps, agitation, allergic rxns rarely
- overdose can result in hyponatremia and seizures
- vasopressin should be used with caution in patients with coronary artery disease due to vasoconstriction
Vasopressin antagonists
- Conivaptan
- Tolvaptan
MOA of the Vaptans
- antagonists of vasopressin receptors
- Tol for V2
- Coni gets both
What is unique about the vasopressin antagonists?
they increase renal free water excretion with little or no change in electrolyte excretion (as opposed to diuretics)
What would we use vasopressin antagonists for?
-tx of euvolemic and hypervolemic hyponatremia
In CHF, which drug increases renal free water excretion without a change in systemic vascular resistance?
Conivaptan
What metabolizes coni/tolvaptan?
CYP3A4
