Pharm: Rx for hypothalamic, pituitary, and thyroid function Flashcards
Somatostatin negatively regulates secretion of:
GH and TSH
Dopamine negatively regulates secretion of:
Prolactin
What effect does HYPOglycemia have on GH release?
What about HYPERglycemia?
HYPO stimulates GH release
HYPER inhibits GH release
Can you measure GH levels in the blood to test for GH deficiency?
No. GH has a pulsatile release, so measurement is meaningless. A series of test stimuli are used for the Dx of GH deficiency.
What effect does GH have on insulin sensitivity?
What does this mean for GH deficient children?
Decreases insulin sensitivity.
GH deficient children can be hypoglycemic due to insulin hypersensitivity.
What effect does GH have on lipolysis?
^ lipolysis
What effect does GH have on IGF-1 production and what effect does this have on protein synthesis and epiphyseal bone growth?
^ IGF-1 production
^ protein synthesis
^ bone growth
Does a deficiency of GH in the fetus result in delayed growth present at birth?
No. GH not needed for prenatal growth.
How does adult GH deficiency present?
General obesity, decreased muscle mass, reduced cardiac output.
What is somatropin?
It is the generic name of all GH that is identical to hGH
Describe the treatment protocol for children with a GH deficiency.
Treatment with hGH is most effective in the 1st 2 yrs. Therapy continues until growth stops.
Few side effects in children. Some develop intracranial hypertension, papilledema, visual changes, headache, n/v
From text: In children, pseudotumor cerebri, slipped capital femoral epiphysis, progression of scoliosis, edema, and hyperglycemia • in adults, peripheral edema, myalgia, and arthralgia.
What malignancy has been reported to follow treatment of children with GH deficiency, especially within two years following treatment of a pediatric tumor.
Leukemia
What happens in IGF-1 deficiency? Is it common? How do you treat it?
It is rare. Children do not respond to hGH. Tx with Mecasermin (a complex of hIGF-1 and hIGFBP3 [for longer half-life])
Children with severe IGF-1 deficiency usually also have IGFB3 deficiency as well.
SFX: Hypoglycemia, intracranial hypertension, increased liver enzymes
How do you tx gigantism and acromegaly?
When pituitary Sx is impossible, tx with somatostatin analogues.
Most widely used: Octreotide or Lanreotide
SFX: GI- diarrhea, nausea, abd pain. Also cardiac conduction abnormalities and gallstones.
Long acting, slow release form: Sandostatin-LAR “think: sustain”
Pegvisomant- GH receptor antagonist, tx of acromegaly (adults). Decreases IGF-1. SFX: Increased liver enzymes
How do you tx hyperprolactinemia?
Surgery, radiation, or use of a dopamine receptor agonist (suppresses prolactin production through D2 receptors)
DRA’s:
Cabergoline- higher affinity for D2 receptor, longer half-life
Bromocriptine- not well tolerated* but FDA approved
*SFX: Gastrointestinal disturbances, orthostatic hypotension, headache, psychiatric disturbances, vasospasm and pulmonary infiltrates in high doses
What is protirelin?
Protirelin- stimulates TSH release from the pituitary. Also used to test thyroid function.
Thyrotropin alpha hTRH- used in Dx of thyroglobulin levels
What is the leading cause of metal retardation world-wide?
HYPOthyroidism
Describe the ratio of T3/T4 released into the blood stream and how synthesis changes during iodine deficiency.
Secreted 1:10 normally (T3/T4)
When iodine deficient, synthesis changes from 4:1 (T4/T3 to 1:3 (T4/T3)
What is the impact on the fetus of low thyroid hormone levels during the 1st trimester of pregnancy? Why?
No effect, fetus gets T3/T4 from mother during 1st trimester. After that, fetus is in trouble.
Describe the biotransformation of T3/T4.
T3/T4 are both metabolized by the liver (glucuronide conjugation and sulfate conjugation) and excreted in the bile. They are thus subject to enterohepatic cycling (reabsorption).
What are the major transporters of T4 in the plasma?
Thyroxine binding globulin (TBG- binds 1:1) and Transthyretin (TTR- binds 2:1 T4:TTR)
True of false:
hormone signal is total T4/T3 in plasma.
False, only unbound.
Describe the immediate, late, and last effects of TSH on the thyroid gland.
Immediate: increased secretion of T3/T4
Late: iodide uptake, hormone synthesis, proteolysis
Last: hypertrophy and hyperplasia of thyroid cells
Describe the TSH receptor.
G-protein couples receptor that stimulates adenylyl cyclase
What can happen as a result of mutations in the TSH receptor in the thyroid follicle?
Increased or decreased activity of the Thyroid gland.
Describe the drug treatment for HYPOthyroidism.
Administration of thyroid hormone (T4 or T3)
Levothyroxine, L-T4
Higher doses req’d for children
May take several wks to reach steady state level
Monitor hormone levels as small differences are important.
Lyothyronine sodium, L-T3
Mixture of T3 & T4: liotrix
Describe the drug treatment for HYPERthyroidism.
Thioureylenes (propylthiouracil [PTU], methimazole, carbimazole) - inhibit iodine organification
PTU also inhibits peripheral activation of T4 –> T3
PTU is rapidly absorbed and has a shorter half-life than methimazole.
Methimazole is also 10x more potent than PTU.
Methimazole can cross the placenta and be concentrated in the fetal thyroid. - so give PTU instead
Due to T3’s potent effects on the heart, this drug is recommended to chill the heart out in hyperthyroidism.
Propranolol (B blocker)
Describe the negative side effects of using Iodine as a contrast agent in CT scans and cardiac catheterization, etc.
It can cause incident hyperthyroidism in euthyroid pts and thyroid storm in hyperthyroid pts
When would use of Iodine be indicated to treat thyroid problems.
Used to treat thyroid storm because it immediately blocks release of thyroid hormone.
Decreases size, vascularity, and fragility of the hyperplastic gland. Useful for pre-operative tx.
Not to be used long-term or prior to radioactive iodide tx.
What can be used to selectively destroy the parenchyma of the thyroid gland and not other tissues?
Na131-I. Administered orally and concentrates in the thyroid gland. No evidence to show radiation induced damage to other organs. Do not use in pregnant women or people under 35yo.
