Kruse - Hypothalamic and pituitary hormones DSA Flashcards
Anterior pituitary hormones: GH and PRL - structure and receptors they activate
Structure - single chain proteins
Activate JAK/STAT activating kinase receptors
Anterior pituitary hormones: TSH FSH, and LH - structure and receptors they activate
Structure - dimeric proteins
Activate GPCRs
Anterior pituitary hormones: ACTH - structure
Structure - single peptide
What inhibits TSH and TRH production?
T4 and T3
What inhibits GSH, LH, and GnRH?
females - estrogen and progesterone
males - androgens
What inhibits ACTH and CRH?
Cortisol
What stimulates GH, what inhibits it?
stimulated by GHRH, inhibited by somatostatin (SST)
What inhibits PRL production?
D2 dopamine receptors predominantly under inhibitory control by this means
What stimulates PRL production?
TRH and hormones of glucagon family (VIP, GIP, secretin, glucagon). BUT release is predominantly under hypothalamic D2 inhibitory control.
*** GHRH(+)/somatostatin(-) (hypothalamic hormones) —> ___ (ant-pit hormone) —> ___ target organ/primary target organ hormone/mediator
GH (somatotropin) –> liver, muscle, bone, kidney (IGF-1)
*** TRH(+) (hypothalamic hormone)—> ___ (ant-pit hormone) —> ___ target organ/primary target organ hormone/mediator
TSH —> thyroid (T4, T3)
*** CRH(+) (hypothalamic hormone) —> ___ (ant-pit hormone) —> ___ target organ/primary target organ hormone/mediator
ACTH —> Adrenal cortex (GC, MC, androgens)
*** GnRH (hypothalamic hormone) —> ___ (ant-pit hormone) —> ___ target organ/primary target organ hormone/mediator
FSH and LH –> gonads (estrogen, progesterone, testosterone)
*** Dopamine (hypothalamic hormone) —> ___ (ant-pit hormone) —> ___ target organ/primary target organ hormone/mediator
PRL —> breast
Name of recombinant form of GH
somatropin
What effect does GH have on insulin sensitivity?
What effect dos IGF-1 have on insulin sensitivity?
reduces it - causes mild hyperinsulinemia
GH –> JAK/STAT –> increased IGF-1 –> growth [IGF-1 increases insulin sensitivity to lower glucose]
A child has short stature and is given something to achieve normal height. What would treatment with this drug combat in adults with the same hormonal deficient?
Drug: rhGH
Adults with GH deficiency have general obesity, reduced muscle mass, asthenia, reduced CO. This GH deficiency could be due to pit or hypothalamus damage.
Syndromes, other than GH-deficiency, that rhGH can help effect stature.
Turner syndrome, prader willi, noonan syndrome
AE of a child with Turner syndrome, hypothyroid, pancreatitis, gynecomastia - taking GH
otitis media, scoliosis, intracranial HTN (vision change, hypothyroid, nausea, vomiting)
An adult has peripheral edema, myalgias, arthraliga, and carpal tunnel syndrome - what are these AE SE of? And what is a CI of this same drug?
GH
CI - malignancy
A child has growth failure with severe IGF-1 deficiency. He does not respond to rhGH. What complex can be given?
Mecasermin - recombinant human IGF-1 and recombinant insulin-like GF-binding protein3 (IGFBP3)
What should a patient taking mescasermin be instructed to do prior to taking the drug - why?
eat 20 minutes before administration, to avoid hypoglycemia.
What can be used to treat ant-pit adenomas (acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, any hormone secreting tumors, etc.) that secrete GH?
GH-antagonists: somatostatin (SST) analogs –> Octreotide and Lanreotide
What SST analogs are particularly approved for tx of acromegaly?
Lanreotide and Pegvisomant
A person with a hormone secreting tumor is given an SST analog. What AE should be watched for?
- GI N/D/pain
- GALLSTONES
- cardiac effects (sinus brady, conduction disturbances)
- B12 deficiency
MOA of pegvisomant v. SST analogs
pegvisomant is a GH receptor antagonist
A person has hyperprolactinemia (i.e. due to prolatinoma), or acromegaly or Parkinson Disease. Give what?
D2 Dopamine receptor agonists - bromocriptine, not cabergoline (only for hyperPRL)
A person presents with HA, dizziness, N, fatigue, PULMONARY INFILTRATES, and possibly psychiatric manifestations. What is he/she taking?
Bromocriptine and cabergoline
If a pregnant woman has a macroadenoma v. microadenoma - can she continue therapy of D2-R agonist?
Macroadenoma - yes, can continue.
Microadenoma - no, discontinue bc microadenoma growth during pregnancy is rare
Why are D2 agonists not recommended to suppress postpartum lactation?
increased risk of stroke or coronary thrombosis.
Peptide hormone released in response to rising plasma osmolality or falling blood pressure.
Vasopressin and desmopressin (ADH)
Difference between desmopressin and vasopressin.
Desmopressin = majority V2, minimal V1 activity (Kidneys) Vasopressin = V1 (CARDIAC/vasoconstrictive effects)
Central DI v. nephrogenic DI will respond how to vaso/desmopressin?
central DI will have an effective increase in urine osmolality (problem with ADH secretion) while nephrogenic will not (problem with kidneys, not ADH)
Vasopressin’s vasoconstrictive effects means that pts with ____ should be carful when taking?
Coronary artery disease - due to the vasoconstriction
A person is having seizures and hyponeatremia - this is due to what?
overdose of vasopressin
A person ahs CHF or SIADH that caused euvolemin and hypervolemic hyponatremia. What drugs should be used?
Vasopressin antagonsists - conivaptan and tolvaptan.
They increase renal free water exretion with no change in electrolyte excretion.
Describe differences between Tolvaptan and Conivapton MOA
Conivaptan - V1 and V2 (nonselective) antagonists
Tolvaptan - V2 selective antagonists
Tolvaptan and Conivapton metabolization
CYP3A4
A woman presents with amenorrhea and galactorrhea. A male presents with loss of libido and infertility. What hormone are they lacking, what drug can be administered?
Symptomatic hyperprolactinemia - treat with D-agonists to inhibit PRL secretion
DOC for central DI
desmopressin preferred, but vasopressin can also be used.
