Hypothalamic and Pituitary Hormones DSA Flashcards
GH
(somatropin)
IGF-1 agonist
mecasermin
Somatostatin analogs
- octreotide
- Lanreotide
GH antagonists
pegvisomant
dopamine agonists
- bromocriptine
- cabergoline
vasopressin R agonists
- vasopressin
- desmopressin
vasopressin R antagonists
- conivaptan
- tolvaptan
anterior lobe
- positively regulated by hypothalamic release Hs (Via the hypothalamic-adenohypophyseal portal system)
- neg regulated by hypothalamic peptides (somatostatin) and catecholamines (dopamine)
posterior lobe
- H’s are syn in neuronal cell bodies in the hypothalamus- transported via axons in the stalk of the pit to the posterior lobe
- vasopresson and oxytocin
GH and PRL- act what?
JAK/STAT
TSH, FSH, LH, ACTH- act what?
GPCRs
TSH release reg by?
TRH
LH and FSH release reg by?
GnRH
ACTH release reg by?
CRH
TSH, FSH, LH, ACTH- feedback inhibitory regulation
- TSH and TRH- inhibited by T3 and T4
- FSH, LH, GnRH- inhibited by estrogen/progesterone and androgens
- ACTH, CRH- inhibited by cortisol
GH production stim and inhibited by?
- stim by GHRH
- inhibited by somatostatin
- GH and IGF-1 feedback to inhibit GH release
prolactin- inhibited by?
- inhibited by dopamine via D2 Rs
- secretion is under inhibitory control by the hypothalamus (dopamine R coupled to Gi)- disruption of pit stalk- inc PRL levels!!
recombinant human form of GH- pharmacokinetics
somatotropin
- metabolized by liver
- lasts 36 hrs (vs endogenous GH- t1/2 is 20 min)
- induces P450s
GH (somatotropin)- pharmacodynamics
- GH Rs dimerize after binding to GH- act JAK/STAT
- inc in IGF-1 prod- growth promoting effects
- stim longitudinal bone growth
- anabolic effects in m and catabolic effects in lipid cells
GH- effects on carbohydrate metabolism
- GH and IGF-1 have opp effects on insulin sensitivity
- GH reduces insulin sensitivity
- IGF-1- lowers serum glucose and reduce insulin
GH- clinical uses
- GH def in children- to achieve normal height
- GH def in adults- present with obesity, reduced m mass, asthenia, reduced CO- tx help reverses these sx’s!
- GH tx of pediatric pts with short stature
- wasting in pts with AIDS
- short bowel syndrome who are dep on parenteral nutrition
GH toxicity and contraindications
- well tolerated in kids- rare: intracranial HTN, scoliosis, otitis media in pts w/ Turner syndrome, hypothyroidism, pancreatitis, gynecomastia
- adults have more adverse effects- peripheral edema, myalgias, arthralgias, carpal tunnel syndrome
- contraindicated in pts with a malignancy!!!
Mecasermin
recombinant IGF-1 and IGFBP-3 (insulin-like growth factor-binding protein)
- some children w/ growth failure have IGF-1 def that isnt responsive to exogenous GH
- subcutaneous admin
- adverse effect- hypoglycemia
GH antagonists- treat what?
ant pit adenomas that secrete GH
- suppress GH secretion (somatostatin analog, dopamine R agonist)
- antagonize the GH R (pegvisomant)
GH Antagonists- types
- somatostatin analogs- Octreotide, Lanreotide
- GH R antagonist- pegvisomant
Octreotide
- most widely used SST analog
- 45x more potent than SST in inhibiting GH release; 2x more potent in reducing insulin secretion
- subcutaneous admin- t/12 is 80 min
- reduces the sx’s of H-secreting tumors!
Lanreotide
-tx acromegaly
SST analogs- adverse effects
- GI (diarrhea, nausea, abd pain)- 50% of pts
- gallbladder sludge and gallstones- dec GB contraction and bile secretion
- cardiac effects (sinus bradycardia, conduction disturbances)
- Vit B12 def
Pegvisomant
- GH R antagonist
- tx acromegaly
- allows R to dimerize but doesnt act the JAK-STAT pathway or stim IGF-1 secretion
for pts with symptomatic hyperprolactinemia- tx?
(women- amenorrhea and galactorrhea; men- loss of libido, infertility)
-inhibition of PRL secretion via dopamine agonist
Dopamine agonists
Bromocriptine and Cabergoline
- D2 R agonist!
- oral or vaginal suppository
Dopamine agonists- clinical use
- hyperprolactinemia
- shrink pit PRL-secreting tumors, lower circulating PRL levels, and restore ovulation in 70% of women with microadenomas and 30% of women with macroadenomas
- can be used with pit surgery, radiation tx, or octreotide admin to treat acromegaly
Dopamine agonists- toxicity and contraindications
- Nausea, HA, light-headedness, orthostatic hypotension, fatigue- most common
- psychiatric manifestations
- pulm infiltrates- high-dose tx
- pts with macroadenomas who are pregnant continue tx
- pts with microadenomas who are pregnant discontinue tx (growth of tumor during pregnancy is rare)
- dopamine agonists are not recommended to suppress postpartum lactation- inc risk of stroke or coronary thrombosis
Vasopressin (ADH)- clinically what is sued
- vasopressin- admin IV or IM
- desmopressin- long-acting synthetic analog of vasopressin; admin IV, subcutaneously, intranasally, or PO
- desmopressin t1/2 is 1.5-2.5 h vs vasopressin t/12 15 min
Vasopressin- moa
- act GPCR V1 Rs (smooth m- vasoconstriction) and V2 Rs (renal tubule cells- inc water permeability and resorption in CTs)
- extrarenal V2-like R- reg release of coag factor 8 and vwF
Vasopressin and Desmopressin- clinical use
- pituitary (central) diabetes insipidus!
- desmopressin is preferred- selectivity of V2 Rs!!
- admin of treatment will help to delineate a diagnosis of CENTRAL DI (effective in inc urine osmolality) or NEPHROGENIC DI (ineffective in inc urine osmolality)
- desmopressin- used to tx coagulopathy in hemophilia A and von willebrand dz
Vasopressin and Desmopressin- toxicity and contraindications
- HA, nausea, abd cramps, agitation, allergic rxns- rarely
- overdose- hyponatremia and seizures
- vasopressin- use in caution in pts with CAD due to vasoconstriction
Vasopressin antagonists- moa
Conivaptan and Tolvaptan
- antagonists of vasopressin Rs
- Tolvaptan- selective for V2 Rs
- Conivaptan- V1 and V2 Rs
- known as “aquaretics”- inc renal free water excretion with little change in electrolyte excretion
Vasopressin antagonists- clinical use
- euvolemic and hypervolemic hyponatremia (ex- in CHF and SIADH
- tolvaptan- in short-term clinical trials with CHF- reduced ejection fraction, dec body weight, and improved dyspnea; but long-term there was no effect on all-cause mortality, CV death, or hospitalization for HF
