Hypothalamic/Pituitary Flashcards
What is GHRH used for?
Recombinant form used to stimulate growth hormone secretion in people with short stature
What is somatostatin used for?
Inhibits release of glucagon, insulin, gastrin, TSH, and growth hormone; an example is Octreotide
What is GnRH used for?
Stimulates release of FSH and LH; when given pulsatile simulates physiological action
What is CRH used for?
Stimulates release of ACTH from anterior pituitary through activation of cAMP
What is TRH used for?
Stimulates release of thyrotropin from anterior pituitary, and prolactin
What does dopamine do in the pituitary pathway?
Inhibits prolactin release
What time of day, and stage of human development do growth hormone and prolactin peak?
At night (around midnight) and puberty
What happens to blood glucose when IGF is increased?
Blood glucose decreases
What happens when too much growth hormone is released?
In childhood you have gigantism, in adulthood you have acromegaly
What drug is used for growth hormone deficiency that is responsive to growth hormone treatment?
Somatropin
What drug treats growth hormone receptor mutation, or abnormal signaling that is not responsive to growth hormone treatment?
Mescasermin (IGF-1 agonist)
Where does somatropin act, and what are it’s effects?
Acts through growth hormone receptors to increase IGF-1; restores normal growth and metabolic defects in GH deficient patients
What are symptoms of somatropin toxicity and what is it contraindicated in?
TOX: Malignancy, papilledema, visual disturbances, GH replacement therapy can cause diabetes mellitus, scoliosis, edema, etc.
CONTRA: Active malignancy
Other than GH deficiency, what are other uses of somatropin?
- Prader-Willi (decrease obesity, growth, and carbohydrate intolerance)
- Turner Syndrome (treated w/ growth factor and gonadal steroid)
- Idiopathic short stature
- Chronic renal failure
- AIDS related wasting
- Malabsorption due to short bowel syndrome.
What is the mechanism of action, and effects of Mescasermin?
Recombinant form of IGF-1 that stimulates the IGF-1 receptors; restores normal growth in patients with a receptor mutation of GH or IGF-1 deficiency who are resistant to GH
What are some Mescasermin toxicities?
Hypoglycemia, intracranial hypertension, increased liver enzymes
What drug is used in gigantism and acromegaly patients?
Somatostatin
What is the mechanism and effects of Octreotide?
Agonist of somatostatin receptors, inhibiting GH production, and to a lesser extent glucagon, insulin, and gastrin
What are some clinical applications of Octreotide?
Acromegaly, carcinoid syndrome, acute bleeding from esophageal varices, diabetic diarrhea, localization of GI serotonin tumor
What are some toxicities of Octreotide?
GI disturbances, gallstones, bradycardia, and other cardiac conductibility disturbances.
What is similar to Octreotide and used in long-acting therapy?
Lanreotide
What is the mechanism of action and some effects of Pegvisomant?
Blocks GH receptors; ameliorates effects of excess GH production in acromegaly patients.
What is the toxicity for Pegvisomant?
Elevated liver enzymes
What is the difference in V1 and V2 for the ADH receptor?
V1 - smooth muscle - vasoconstriction
V2 - kidney - aquaporin - water resorption
What is the mechanism and effects of Atosiban?
Blocks oxytocin receptors causing decreased uterine contractions; tocolysis for preterm labor.
What are some toxicities of Atosiban?
Concern about rates of increased infant deaths.
NOTE: This is the first IV drug administration, the GH ones were subcutaneous
What does vasopressin (ADH) do, and what is it used for?
Activates V2 to increase water permeability and resorption, concentrating urine. Used in Central Diabetes Insipidus
Activates V1 to cause vasoconstriction. Used in variceal or controlled bleeding.
What are side effects of vasopressin (ADH)?
Hypertension and bradycardia
What is the mechanism of action of Desmopressin, and some effects?
Activates vasopressin (V2 > V1) receptors; so agonist, acts in kidney to decrease excretion of water, acts on extra-renal V2 receptors to increase Factor VIII & Von Willebrand
What are the clinical applications, route of administration, and toxicities of Desmopressin?
- Pituitary diabetes inspidius, hemophilia A & Von Willebrand disease, nocturnal enuresis.
- Oral, IV, SC, or nasal
- GI disturbances, headache, hyponatremia, allergic rxns
What is the water deprivation test, and how is it interpreted?
- Diagnose between central and nephrogenic diabetes insipidus.
- Normal person the urine after water deprivation and desmopressin is >750 mOsmol/kg; diabetes insipidus is <300 mOsmol/kg. Central if increases after AVP, nephro if not changed by AVP
What is SIADH and the treatment for it?
Inappropriate secretion of ADH, usually caused by tumor or injury in lung/brain, characterized by low blood sodium
Tx: Restrict water intake, hypertonic saline, Conivaptan, Demeclocycline, and Lithium
What are some important side effects of lithium?
Nephrogenic diabetes insipidus, and hypothyroidism
What is the mechanism of action, how it’s administered and some effects of Conivaptan?
Antagonist of V1a and V2 receptors, which increases renal excretion of water. Used for hyponatremia patients in hospitalized SIADH.
Administered via IV
What are symptoms of microadenoma of the pituitary and what is it treated with?
Amenorrhea, galactorrhea, treated with bromocriptine and cabergoline. More common in females.
What are the symptoms of macroadenoma of the pituitary and what is it treated with?
Visual field defect, treated with surgery (trans-sphenoid approach) and radiation. More common in males.
