Hp, Pit, and thyroid Drugs

Question 1

What are the hormones of the anterior pituitary?

Answer 1

prolactin, gonadotropic hormones (FSH, LH), thyroid-stimulating hormones, ACTH, growth hormones.

Question 2

What inhibits secretion of prolactin?

Answer 2

dopamine

Question 3

What negatively regulates TSH and GH?

Answer 3

somatostatin (negative feedback on AP)

Question 4

what are the thyrotropin releasing hormones?

Answer 4

prolactin and TSH

Question 5

what are the gonadotrophin releasing hormones?

Answer 5

FSH and LH

Question 6

What are the corticotrophin releasing hormones?

Answer 6

ACTH

Question 7

what are the growth hormone releasing hormones?

Answer 7

GH

Question 8

Features of GH

Answer 8

-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.

Question 9

In terms of blood sugar, what stimulates GH?

Answer 9

hypoglycemia

Question 10

GH antagonizes what?

Answer 10

insulin. GH deficient children can have HYPOglycemia.

Question 11

how can neonates have GH deficiency?

Answer 11

genetics or trauma during delivery to pituitary

(GH not needed for prenatal growth so neonates may be normal size)

Question 12

What does GH deficiency in adults result in?

Answer 12

general obesity, reduced muscle mass and reduced cardiac output

Question 13

Somatotropin. What is it for?

Answer 13

for GH deficiency; identical with hGH

Question 14

what is Sermorelin acetate?

Answer 14

-hGHRH- available for dx of GH deficiency in children but now discontinued by manufacturer

Question 15

GH tx features

Answer 15

• 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.

Question 16

Side effects of GH tx in children?

Answer 16

• 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

Question 17

Side effects of GH tx in adults?

Answer 17

peripheral edema, carpal tunnel syndrome, arthralgia, and myalgia

Question 18

why is GH and GHRH drug abused? and by whom?

Answer 18

• 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.

Question 19

what is the primary mediator of GH?

Answer 19

IGF-1.
GH has many direct effects like on bone, muscle, fat and liver but it can also target tissues to produce IGF-1.

Question 20

Where is igf-1 made and where are its effects?

Answer 20

Made in liver and acts primarily on muscle, bone, and fat.

Question 21

In adults, GH can be used to decrease the mortality of what diseases?

Answer 21

Cardiovascular disease and AIDS associated wasting

Question 22

in IGF-1 deficiency, people respond to what drug?

Question 23

What are somatostatin analogs used for? Name some drugs in this class

Question 24

which somatostatin analog drug is long-acting and is in a slow-release form?

Question 25

What are the side effects of Somatostatin analogs?

Question 26

MOA of pegvisomant? what is it used in the treatment of?

Answer 26

growth hormone receptor antagonist

Question 27

What can cause hyperprolactinemia? What are side effects of hyperprolactinemia?

Answer 27

- 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

Question 28

What is the tx of hyperprolactinemia?

Answer 28

- 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.

Question 30

MOA of protirelin and what is it used for?

Answer 30

- stimulates TSH release from the pituitary and is used to test thyroid function

Question 31

What is thyrotropin alpha hTRH (Thyrogen) used for?

Answer 31

-used in the diagnostics for thyroglubulin levels

Question 32

What are the actions of thyroid hormones?

Answer 32

- growth and devleopment - calorigenic- increased o2 consumption - cardiovascular- increased HR and force of contraction - metaboic- maintain homeostasis

Question 33

why and when does fetus need TH?

Answer 33

- during first trimester of preggo, fetus needs TH from mom (bc they dont make any) for normal brain development and for heart development.

Question 34

Biotransformation of thyroid hormones

Answer 34

- 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**

Question 35

How are thyroid hormones transported?

Answer 35

-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.

Question 36

MOA of thyroid hormones

Answer 36

- 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

Question 37

What drugs used to treat HYPOthyroidism?

Answer 37

- 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 -

Question 38

What drugs are used for tx of HYPERthyroid

Answer 38

- thiourelenes like PTU and methimazole - carbimazole

Question 39

MOA thioureylenes like PTU and methimazole? which one has shorter plasma half life? which more more potent? which one used in pregnancy?

Answer 39

- 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

Question 40

side effects of thioureylenes?

Answer 40

skin rash and in severe cases agrunolyctosis

Question 41

tx for thyroid storm and pre-operative cases?

Answer 41

- 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

Question 42

MOA of radioactive iodine and clinical application?

Answer 42

- 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!!!