Hypothalamic and Pituitary Pharmacology Flashcards Preview

DEMS: Unit III > Hypothalamic and Pituitary Pharmacology > Flashcards

Flashcards in Hypothalamic and Pituitary Pharmacology Deck (17)
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Releasing (sermorelin) vs. replacement (recombinant GH) therapy in tx of hypo-GH

  • Sermorelin (synthetic GHRH) is less effective than recombinant GH and not effective if GH deficient due to pituitary dysfunction.
  • Recombinant GH (Somatropin, Somatrem) work indirectly to stimulate synthesis of IGF (aka somatomedins (SM)) which stimulate growth of bones and muscles directly.



Tx of GH resistance

  • If resistant to GH (mutated receptor), treat with recombinant IGF-1.



Drug that stimulates release of GH



Drugs that inhibit release of GH

  • octreotide = analog of somatostatin 
  • bromocroptine = DA (D2) receptor agonist


Role of octreotide in GH hypersectretion treatment

  • Analog of somatostatin → ↓ GH, glucagon, insulin, TSH release
  • Long t1/2
  • Selective for GH over insulin,
  • subQ injection 3x/day
  • Lanreotide is long-acting; IM injections q 10-14d.


Role of bromocriptine in GH hypersecretion treatment

  • DA receptor (D2) agonist with paradoxical
  • ↓ in GH in some patients with acromegaly.
  • Possibly best if tumor secretes both GH & PRL.
  • Semisynthetic ergot alkaloid. Used for both GH & PRL tumors.
  • Dopamine ↓ GH if it is a weird tumor where lactotrophs are secreting GH


Structure, pharmokinetics, actions of vasopressin

  • Vasopressin: Interacts with V1 and V2 receptors. Administered every 3 days, dosage forms include SC, IM, IV
  • V1 coupled to PLC (Gq) →IP3 & DAG → ↑Ca2+ & PKC.
  • V2 → Gs → ↑cAMP → ↑PKA → exocytosis of aquaporin-containing vesicles, thus ↑ water reabsorbtion


Vasopressin action at V1 receptors

  • V1 coupled to PLC (Gq) →IP3 & DAG → ↑Ca2+ & PKC. 
  • V1a receptors in vascular smooth muscle mediate vasoconstriction.
  • ↑ glycogenolysis, platelet aggregation, ACTH release (V1b), vascular smooth muscle cell growth.


Vasopressin action at V2 receptors

  • V2 → Gs → ↑cAMP → ↑PKA → exocytosis of aquaporin-containing vesicles, thus ↑ water reabsorbtion
  • ↑ Permeability of urea (more concentrated urine) and
  • ↑ NaCl transport in thick ascending limb
  • ↑ Osmolarity of interstitial fluid in kidney medulla


Drugs used to treat DI & SIADH

  • DI: hypofunction of vasopressin, excess urine
    • Treat with DDAVP, vasopressin (pitressin), chlorpropamide
  • SIADH: hyperfunction of vasopressin, dilutional hyponatremia
    • treat with demeclocycline (blocks vasopressin-induced cAMP generation)


Causes of nephrogenic diabetes insipidus

  • Li+ → inhibits cAMP
  • Cisplatin, colchicine, gentamycin, rifampin, propoxyphene also cause it
  • Chronic hypercalcemia and hypokalemia
  • Mutations in receptors or aquaporins


Causes of neurogenic diabetes insipidus

  • Defective synthesis & release ADH due to
  • Pituitary surgery
  • Craniopharyngioma
  • TBI
  • Autoimmune disorders
  • Phenytoin
  • Idiopathic


Drug causes of SIADH

  • SSRI’s
  • Amiodarone
  • Carbemazapine
  • Chloropromazine
  • Amiltryptiline


Possible (non-drug) causes of SIADH

  • Pulmonary infections and cancer
  • Malignancy
  • CNS disorders


Clinical manifestation of diabetes insipidus

  • untreated central DI typically present with polyuria, nocturia, and, due to the initial elevation in serum sodium and osmolality, polydipsia.
  • They may also have neurologic symptoms related to the underlying neurologic disease.



Sodium levels in DI

  • serum sodium concentration in untreated central DI is often in the high normal range, which is required to provide the ongoing stimulation of thirst to replace the urinary water losses.
  • Moderate to severe hypernatremia can develop when thirst is impaired or cannot be expressed.
  • This can occur in patients with central nervous system lesions who also have hypodipsia or adipsia, in infants and young children who cannot independently access free water, and in the postoperative period in patients with unrecognized DI.