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E2T1 > Hypothalamic and Pituitary Hormones DSA > Flashcards

Hypothalamic and Pituitary Hormones DSA Flashcards

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1
Q

GH

A

(somatropin)

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2
Q

IGF-1 agonist

A

mecasermin

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3
Q

Somatostatin analogs

A
  • octreotide

- Lanreotide

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4
Q

GH antagonists

A

pegvisomant

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5
Q

dopamine agonists

A
  • bromocriptine

- cabergoline

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6
Q

vasopressin R agonists

A
  • vasopressin

- desmopressin

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7
Q

vasopressin R antagonists

A
  • conivaptan

- tolvaptan

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8
Q

anterior lobe

A
  • positively regulated by hypothalamic release Hs (Via the hypothalamic-adenohypophyseal portal system)
  • neg regulated by hypothalamic peptides (somatostatin) and catecholamines (dopamine)
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9
Q

posterior lobe

A
  • 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
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10
Q

GH and PRL- act what?

A

JAK/STAT

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11
Q

TSH, FSH, LH, ACTH- act what?

A

GPCRs

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12
Q

TSH release reg by?

A

TRH

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13
Q

LH and FSH release reg by?

A

GnRH

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14
Q

ACTH release reg by?

A

CRH

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15
Q

TSH, FSH, LH, ACTH- feedback inhibitory regulation

A
  • TSH and TRH- inhibited by T3 and T4
  • FSH, LH, GnRH- inhibited by estrogen/progesterone and androgens
  • ACTH, CRH- inhibited by cortisol
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16
Q

GH production stim and inhibited by?

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A
  • stim by GHRH
  • inhibited by somatostatin
  • GH and IGF-1 feedback to inhibit GH release
17
Q

prolactin- inhibited by?

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A
  • 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!!
18
Q

recombinant human form of GH- pharmacokinetics

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A

somatotropin

  • metabolized by liver
  • lasts 36 hrs (vs endogenous GH- t1/2 is 20 min)
  • induces P450s
19
Q

GH (somatotropin)- pharmacodynamics

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A
  • 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
20
Q

GH- effects on carbohydrate metabolism

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A
  • GH and IGF-1 have opp effects on insulin sensitivity
  • GH reduces insulin sensitivity
  • IGF-1- lowers serum glucose and reduce insulin
21
Q

GH- clinical uses

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A
  • 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
22
Q

GH toxicity and contraindications

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A
  • 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!!!
23
Q

Mecasermin

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A

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
24
Q

GH antagonists- treat what?

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A

ant pit adenomas that secrete GH

  • suppress GH secretion (somatostatin analog, dopamine R agonist)
  • antagonize the GH R (pegvisomant)
25
GH Antagonists- types
- somatostatin analogs- Octreotide, Lanreotide | - GH R antagonist- pegvisomant
26
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!
27
Lanreotide
-tx acromegaly
28
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
29
Pegvisomant
- GH R antagonist - tx acromegaly - allows R to dimerize but doesnt act the JAK-STAT pathway or stim IGF-1 secretion
30
for pts with symptomatic hyperprolactinemia- tx?
(women- amenorrhea and galactorrhea; men- loss of libido, infertility) -inhibition of PRL secretion via dopamine agonist
31
Dopamine agonists
Bromocriptine and Cabergoline - D2 R agonist! - oral or vaginal suppository
32
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
33
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
34
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
35
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
36
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
37
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
38
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
39
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

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