24.6 Pharm: Drug effects on HPA axis

Question 1

What does GHRH R’ do?

What does Ghrelin R’ do?

Answer 1

Elevates cAMP

Elevates Ca2+

Question 2

What happens if you administer GH orally?

Answer 2

Zero bioavailability (short half life)

Question 3

What is the normal axis that results in GH release?

Answer 3

Ghrelin/GHRH from the hypothalamus, stimualtes GH release from the pituitary.

Then IGF-1 (liver) is stimulated

(Somatostatin prevents GH release)

Question 4

Describe GH abnormalities:

Insensitivity
Secondary (deficiency)
Tertiary (deficiency)

Answer 4

Insensitivity (self explanatory)

Secondary (GH doesn’t get released)

Tertiary (No Ghrelin/GHRH)

Question 5

What can we use for GH insensitivity?

What is a side effect?

Answer 5

IGF-1 (hypoglycaemia)

Question 6

What do we see in adults with excess GH?

Answer 6

Acromegaly

Question 7

How can we find a tumour that is altering GH?

Answer 7

Look for the somatostatin R’ by giving radioactive iodine

Question 8

Why don’t we use somatostatin to reduce GH?

Answer 8

Short half life
Rapidly degraded (enzymes)
Filtered (kidneys)

Question 9

What are some somatostatin analogues?

How do they work?

What can we sometimes add?

Answer 9

Octreotide, Lanreotide

Resist cleavage (amino acid alteration) for increased half life

Dopamine agonist

Question 10

How does PEGylation improve half life?

Answer 10

Size reduces renal filtration

Hydrophilicity improves solubility

Decreased access for proteolytic enzymes

Question 11

What can we use to ablate the thyroid gland?

Answer 11

Radioactive I- 131

Question 12

What can we give to people with hyperthyroidism? (2)

What do these inhibit?

Answer 12

Carbimazole (inhibits thyroid peroxidase), 1x daily dosing

Propylthiouracil (inhibits thyroid peroxidase and T4–>3 conversion)
2-4 doses/day

Question 13

What can we use for hypothyroidism? (2)

Answer 13

Liothyronine (T3)–> only use in severe cases

Thyroxine (T4)-slow accumulation/onset