Hp, Pit, and thyroid Drugs Flashcards
What are the hormones of the anterior pituitary?
prolactin, gonadotropic hormones (FSH, LH), thyroid-stimulating hormones, ACTH, growth hormones.
What inhibits secretion of prolactin?
dopamine
What negatively regulates TSH and GH?
somatostatin (negative feedback on AP)
what are the thyrotropin releasing hormones?
prolactin and TSH
what are the gonadotrophin releasing hormones?
FSH and LH
What are the corticotrophin releasing hormones?
ACTH
what are the growth hormone releasing hormones?
GH
Features of GH
-pulsatile release; has direct effects but also acts on some tissues to produce IGF-1 - GH negatively feedbacks on hypothalamus and AP -IGF-1 negatively feedbacks on AP. - hypoglycemia stimulates GH release -hyperglycemia inhibits GH release.
In terms of blood sugar, what stimulates GH?
hypoglycemia
GH antagonizes what?
insulin. GH deficient children can have HYPOglycemia.
how can neonates have GH deficiency?
genetics or trauma during delivery to pituitary
(GH not needed for prenatal growth so neonates may be normal size)
What does GH deficiency in adults result in?
general obesity, reduced muscle mass and reduced cardiac output
Somatotropin. What is it for?
for GH deficiency; identical with hGH
what is Sermorelin acetate?
-hGHRH- available for dx of GH deficiency in children but now discontinued by manufacturer
GH tx features
- hGH therapy most effective in first 2 years of life and continues until growth stops
- men tx with hGH have increased muscle and bone and decreased fat.
Side effects of GH tx in children?
- develop intracranial hypertension, papilledema, visual changes, headache, nausea, and vomiting
- Leukemia reported following GH therapy in children so not used within 1-2 years post tx of peds tumors
- increased muscle and bone with decreased fat
Side effects of GH tx in adults?
peripheral edema, carpal tunnel syndrome, arthralgia, and myalgia
why is GH and GHRH drug abused? and by whom?
- in adults it increase muscle mass and decrease adipose tissue mass.
- athletes abuse both but sermorelin (hGHRH) escapes detection in drug testing.
- No evidence for drug improving athletic performance.
what is the primary mediator of GH?
IGF-1.
GH has many direct effects like on bone, muscle, fat and liver but it can also target tissues to produce IGF-1.
Where is igf-1 made and where are its effects?
Made in liver and acts primarily on muscle, bone, and fat.
In adults, GH can be used to decrease the mortality of what diseases?
Cardiovascular disease and AIDS associated wasting
in IGF-1 deficiency, people respond to what drug?
What are somatostatin analogs used for? Name some drugs in this class
which somatostatin analog drug is long-acting and is in a slow-release form?
What are the side effects of Somatostatin analogs?
MOA of pegvisomant?
what is it used in the treatment of?
growth hormone receptor antagonist
What can cause hyperprolactinemia?
What are side effects of hyperprolactinemia?
- Caused by pituitary adenomas or diseases interfering with dopamine signaling
- side effects include galactorrhea, amenorrhea, and infertility in women. Loss of libido, impotence, and infertility in men
What is the tx of hyperprolactinemia?
- Tx is with surgery and radiation and use of dopamine receptor agonists that suppress prolactin production via D2 receptors
- D2 R agonist drugs include cabergoline and bromocriptine.
**Cabergoline has higher affinity for D2 R with longer t1/2 and bromocriptine is not well tolerated even though it is FDA approved.
MOA of protirelin and what is it used for?
- stimulates TSH release from the pituitary and is used to test thyroid function
What is thyrotropin alpha hTRH (Thyrogen) used for?
-used in the diagnostics for thyroglubulin levels
What are the actions of thyroid hormones?
- growth and devleopment
- calorigenic- increased o2 consumption
- cardiovascular- increased HR and force of contraction
- metaboic- maintain homeostasis
why and when does fetus need TH?
- during first trimester of preggo, fetus needs TH from mom (bc they dont make any) for normal brain development and for heart development.
Biotransformation of thyroid hormones
- Both t3 and t4 are metabolized in the liver through glucuronide conjugation and sulfate conjugation.
- Both of these are excreted through bile
- Both are subject to enterohepatic cycling
How are thyroid hormones transported?
-Mostly be by TBG (thyroxine binding globulin) - T4 more tightly bound than t3
- TTR (transthyretin)- higher levels in blood for TTR than TBG. TTR also transport t4 in CSF o.O
- ALbumin- transport both t3 and t4.
** mutated albumin that binds more t4 than t3 so you have high t4 and normal t3 and tsh. Don’t treat those patients since they are not hypothyroid. It is dangerous to treat them.
MOA of thyroid hormones
- act through binding to nuclear receptors
- T3 binds to specfic receptor proteins, TRalpha1 and TRbeta1 and TRbeta2, that bind to specific DNA sequences that upregulate or downregulate DNA transcription
- T4 can bind to these receptors BUT it cant regulate transcription
- RXR bound to TR required for thyroid hormone action
What drugs used to treat HYPOthyroidism?
- administration of levothyroxine, l-t4; liothyronine sodium, l-t3
- mixture of t4 and t3 in liotrix
- higher dose needed for children
- take several weeks to reach steady state level
-
What drugs are used for tx of HYPERthyroid
- thiourelenes like PTU and methimazole
- carbimazole
MOA thioureylenes like PTU and methimazole?
which one has shorter plasma half life?
which more more potent?
which one used in pregnancy?
- inhibit htyroid peroxidase reactions, iodine orgnification, and peripheral conversion of t4 to t3
- PTU has shorter plasma t1/2
- methimazole is 10 more potent
- PTU preferred in pregnancy bc there’ sless placental transfer and limited excretion in milk
side effects of thioureylenes?
skin rash and in severe cases agrunolyctosis
tx for thyroid storm and pre-operative cases?
- large doses of iodine because it rapidly blocks release of thyroid hormone
- decreases size, vascularity, and fragility of the hyperplastic gland
- dont use before radioactive iodine tx
**works best for preop tx or with other antithyroid drugs
MOA of radioactive iodine and clinical application?
- radiation induced destruction of thyroid parynchema and used in tx of hyperthyroidism
***used in tx in adults 35 years or older but not in women of child-bearing age!!!
