Drug Effects on the Hypothalamic Pituitary Axis Flashcards Preview

Gabe's Endocrinology > Drug Effects on the Hypothalamic Pituitary Axis > Flashcards

Flashcards in Drug Effects on the Hypothalamic Pituitary Axis Deck (57)
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1

Where is growth hormone released from?

Anterior pituitary

2

What is growth hormone released in response to?

GHRH and Ghrelin signals from the hypothalamus

3

What does Ghrelin play a role in peripherally?

Appetite

4

What does growth hormone stimulate?

Liver to synthesise and release IGF-1

5

What do IGF-1 and somatostatin do in the blood?

Act as a negative feedback loop to the pituitary, inhibiting GH release

6

Where are the 3 different places growth hormone release can go wrong?

  1. Growth hormone insensitivity: GH doesn’t work – won’t stimulate release of IGF-1
  2. Secondary deficiency: pituitary doesn't produce GH
  3. Tertiary deficiency: no release of GH because hypothalamus doesn't release Ghrelin or GHRH

7

What happens to GH levels in growth hormone insensitivity?

Levels are elevated because IGF-1 isn't released, inhibiting GH release.

8

What is growth hormone also known as?

Somatotropin

9

Why can't growth hormone supplement be administered orally?

Because there is zero bioavailability after oral adminstration - it is broken down and digested.

10

How is growth hormone administed?

By injections, multiple times a day because of its short half-life.

11

What is common among HRT therapies?

Titrating the dose until effect is seen.

12

What can GH cause a reduced level of?

Thyroxine (T4)

13

What role does Ghrelin play in GH release?

Ghrelin receptor elevates Ca2+ and the GHRH receptor elevates cAMP, acting synergistically.

14

When is IGF-1 administered?

In patients with GH insensitivity (e.g. Laron dwarfism) and patients with anti-GH antibodies.

15

What happens if there's not enough growth hormone?

Stunted growth

16

What happens if there's too much growth hormone?

Depending on what time in development, e.g. acromegaly (often caused by GH-releasing tumour)

17

What are the treatment options for too much growth hormone?

  • Remove tumor (if relevant)
  • Reduce GH release
  • Inhibit GH action

18

Which therapeutics can reduce GH release?

Somatostatin analogues and dopamine agonists (can stimulate a reduction in GH release from pituitary)

19

How can GH action be inhibited?

Pegvisomant - GH antagonist

20

How can neuroendocrine tumours be imaged?

  • Somatostatin receptors internalise upon activation (like many GPCRs), taking the tagged peptide ligand with them
  • Tumors expressing somatostatin receptors can be imaged by in vivo receptor scintigraphy

21

Do tumour cells expressing receptors for somatostatin respond to somatotatin?

Yes - they reduce secretion of GH

22

Why does somatostatin only work for a short period of time?

Because it has a short half-life, undergoes enzymatic cleavage and renal elimination

23

How can somatostatin be modified to extend its half-life?

Modify it by adding D amino acids - humans can't cleave D amino acids, giving octreotide and lanreotide.

24

How do you get Pegmisovant?

Turn GH into an antagonist and improve its pharmacokinetics and dynamics.

25

What type of a receptor does GH bind to?

Tyrosine kinase receptor

26

What happens when GH binds to its receptor?

The tyrosine kinase receptor dimerises, with the binding sites on both GH receptor monomers binding to GH.

27

What is G120K-GH?

A GH receptor antagonist that binds one GH receptor monomer but blocks dimerisation by filling the second monomers cleft with lysine.

28

Why does G120K need to be PEGylated?

Because it still has a short half-life, like GH.

29

What is PEGylation?

Conjugation of the bioactive (e.g. G120K-GH) molecule with PEG polymer chains.

30

What does PEGylation achieve?

  • Increase in molecule size, reducing renal filtration.
  • PEG is hydrophilic, improving solubility.
  • Decreased proteolytic enzmyme accessibility