Pharmacology of Hypothalamus & Pituitary Disorders § Use: children w/ GH insensitivity syndrome from GH receptor mutation/Laronn Syn or mutation post

• Hormones secreted by the hypothalamus & pituitary are peptides or low molecular weight proteins.
• Hypothalamus synthesis the precursor proteins of the hormones vasopressin/ADH and oxytocin and are stored in posterior
pituitary.
• Hormones of anterior & posterior pituitary are administered either IM, SC or intranasally. Never oral bc peptides are destroyed
by digestive proteolytic enzymes
• Hypothalamus & Anterior Pituitary.
o Somatotropinà Use JAK/STAT cytokine receptors which contain extracelluar hormone-binding domain,
membrane spanning region, intracellular domain. Binding GH molecule to extracellular domain induces
dimerization & activates.
Modulate gene expression.
§ Most effects are Indirect mediated by somatomedins/IGF—stimulate skeletal growth until epiphysis
close. Anabolic effects in muscle & catabolic in lipid cells.
§ Regulation: GNRH binding to pituitary somatotrophs inc intracellular cAMP & Ca, act w/ Ghrelin to
release GH.
§ Uses: dwarfism growth retardation in childhood, growth failure despite normal GH levels (turner synd,
nooan, prader-willi), GH deficiency in adults, Wasting in HIV infection, malabsorption asso w/ short
bowel synd
o Insulin Like Growth Factors 1à very similar to insulin, ca be activated by insulin and insulin receptors can be
activated by IGF1
GHs ignaling pathway o Growth Hormone
o Growth Hormone Inhibiting Hormones/Somatostatins excreted by the hypothalamus, inhibits GH secretion
from pituitary. Short duration of action & may effects so limited therapeutic usefulness. Also found in other
parts of brain, pancrease/delta cells & GI tract.
o Prolactin
§ Regulators: inhibited by dopamine, androgens, D2-agonist; Stimulated by: suckling, TRH, VIP, estrogen,
stress, exercise, deep sleep, hypoglycemia, histamine, serotonin, substance P, endogenous opioids, D2
antagonist.
§ Action: stimulate breast growth & milk production, inhibit ovulation. Excessive: can lead to
gynecomastia, amenorrhea, galactorrhea, low libido, ED, infertility.
• Pituitary hormones are synthesized in hypothalamus & stored in posterior pituitary. Susceptible to proteolytic
cleavage, must give parenterally.
o Oxytocinà\ secreted by paraventricular cells. Function to contract uterine muscle & elicit milk ejection from
breast vis myoepithelial contraction.
o ADH/Vasopressin Stimulate V1a (vascular smooth muscle), V1b (CNS & adrenal medulla), V2 receptors
(renal tubules, release of Coag factors). deficiency results in Diabetes insipidus. Secreted in response to rising
plasma osmolarity or falling BP. Cause antidiuretic & vasoconstrictive effects, and stimulates hepatic synthesis
of coag factor 8 & vWF.
• Drugs Stimulate: NSAID, carbamazepine, Vinca Alkaloids
• Drugs Inhibit: lithium, demeclocycline, colchicine

Drug MA PK Effect USE AE/CI

Hypothalamus
Somatropin Recombinant of GH

Mecasermin Recombinant IGF-1, activated specific IGF 1 on cell children w/ GH insensitivity Hypoglycemia must have snack 20min before
surface. syndrome from GH receptor dose.
mutation/Laronn Syn or mutation post GH-
signaling pathway
Growth Hormone 70% SC bioavail ½: 2hrs Child: Scoliosis, ICP, hyperglycemia, Otitis Media
Adult: more, peripheral edema, headache,
arthralgias, myalgia, paresthesia,
hyperglycemia, nerve numbness, muscle, joint
pain. slipped cap femoral

CI: DM retinopathy, epiphyseal closure in child,

acute clinical illness, neoplastic disease.

Octreotide Synthetic analog of Growth Hormone Inhibiting SC/IM monthly depot. Inhibits all exocrine & endocrine Nausea, abd cramps, diarrhea, achlorhydria
Hormones/Somatostatin: 45 times more potent than secretion of pancreas, (gastrin inhibited), steatorrhea (inhibit secretin
activates somatostatin receptors dec cAMP and inhibit somatostatin. stomach, intestine, parathyroid. Gigantism & acromegaly & CCK), gallstones, hyperglycemia, sinus brady,
GH secretion. hypothyroid.
Reduce symps of hormone-secreting
Cabergoline D2 receptor agonist tumors, esophageal varices, diarrhea
Pegvisomant Receptor antagonist of GH.

Bids GH receptor but does not activate JAK-STAT

signaling or stimulate IGF-1
Bromocriptine D2 receptor agonists. Oral/vaginal nausea, anorexia, vomitting, constipation,
& Activate central & peripheral D2 Prolactin secreting adenomas (can shrink postural hypoTN, dyskinesias (after logterm
Cabergoline Directly activate non-innervated D2 B  ½: 10hrs receptors. tumor), hyperprolactinemia, acromegaly. use), headache, insomnia, nightmares. Digital
receptors of pituitary mammotroph cells; dec dopa C ½: 65hrs Reduce plasma vasospasm,
turnover inn arcuate nucleus. prolactin levels, block GH & erythromelalgia
IGF-1 release in acromegaly.
CI: psychotic disorders, hyperTN, fibrotic
disorders.
Posterior Pituitary
Oxytocin Act via G protein & PI to inc Ca++, stimulate release of IV infusion: for Induct & maintain labor, stimulate milk HTN crisis if given w/ sympathomimetic, fetal
PG & LT. delivery/bleeding ejection, distress, placental

IM: for bleeding. Nasally: milk ejection control post-partum hemorrhage. abruption, fluid retention/water intoxication.

CI: cephalon-pelvic disproportion.

Desmopressin Vasopressin Analog. More ADH action less IV/ Intranasaly; Pituitary diabetes insipidus, advanced Water intoxication, hyponatremia, headache,
vasoconstrictive effect, stim extrarenal V2 receptor cardiac life support. bronchoconstriction, tremor.
mediate release of coag factor vWF. Log-acting synthetic analog.
CI: CAD, epilepsy, asthma require extra caution.
Terlipressin Vasopressin analog for V1. Cause GI & vascular smooth Dec bleeding, esophageal varices,
muscle contractionn catecholamine resistant shock.
Conivaptan, Tolvaptan ADH antagonist SIADH