Growth hormone agonist and antagonists Flashcards
What are the routes of administration of GH drugs?
1) Subcutaneous
2) Intramuscular
What are the six hormones that are secreted by the adenohypophysis?
1) Corticotropin (adrenocorticotropic hormone (ACTH))
2) Somatotropin (growth hormone)
3) Follicle-stimulating hormone (FSH)
4) Leutinizing hormone (LH)
5) Thyrotropin (TSH)
6) Prolactin
What are the hormones that are secreted by the hypothalamus?
1) corticotropin-releasing hormone
2) growth hormone-releasing hormone (GHRH)
3) somatostatin (growth hormone-inhibiting hormone = GHIH)
4) gonadotropin-releasing hormone (GnRH)
5) thyrotropin-releasing hormone (TRH)
6) dopamine (prolactin-inhibiting hormone [PIH])
Other than GH, what does somatostatin inhibit?
Digestion and TSH
What are the actions of growth hormones?
- GH (somatotropin) is produced by the ant.pituitary, with both a direct and indirect effect on the target organ
- It acts directly to stimulate lipolysis and antagonize insulin to elevate blood glucose levels
- Most of the effects of GH are mediated by the IGF-1 peptides which are produced in the liver and cartilage, and stimulate the skeletal muscle growth, amino acid transport, protein synthesis, nucleic acid synthesis, and cell proliferation
- GH secretion is stimulated by GHRH and inhibited via GHIH
What are the growth hormone preparations?
- We cant use animal growth hormones and that’s why we have a recombinant technology
1) Recombinant somatropin (biosynthetic form of human growth hormone) is used to treat children with various forms of growth hormone deficiency
- Somatotropin preparations have been proven to be active in improving height speed and final height in children
- Somatotropin is administered subcutaneously, once daily to children with GH deficiency
- Not daily drugs:
2) A once-weekly analog of GH (Somapacitan, sogroya) has been approved for adults and it is under phase 3 of clinical trials in children
3) Once weekly prodrug of somatropin (lonapegsomatropin, skytrofa) has been approved for children and it is under investigation for adults
What are the different GH replacement drugs we have?
1) Recombinant somatotropin (once daily)
2) Somapacitan (once weekly for adults)
3) Lonapegsomatropin (once weekly for kids)
What are the recombinant forms of IGF-1?
Mecasermin
What is mecasermin?
- A recombinant form of human IGF-1
- Indicated for the treatment of growth failure in children with severe primary IGF-1 deficiency, GH receptor mutation, and people who developed neutralizing antibodies to GH
- Due to the insulin-like effect patients should be monitored, and they should take it with a meal
When is mecasermin used?
- Normal GH levels but:
1) Mutated receptor (laron syndrome)
2) Patient develops antibodies against GH
3) GH is unable to release IGF-1
What is the side effect of mecasermin?
Hypoglycemia
Which drug is indicated for children with severe IGF-1 deficiency, growth hormone receptor mutation, and neutralizing antibodies to GH?
IGF-1
What is Sermorelin?
- A synthetic GHRH that is approved to treat Idiopathic GH deficiency in children
- It is less effective than recombinant GH
- Used in children with GH deficiency due to hypothalamic damage
- Administered subcutaneously
Which drug is used for idiopathic GH deficiency?
Sermorelin
Which drug is a recombinant of GHRH?
Sermorelin
Which drug is used due to GH from hypothalamic damage?
Sermorelin
What is the effect of glucocorticoids on the growth-promoting effects of recombinant GH?
It might inhibit it
- Growth failure is common during long-term treatment with glucocorticoids due to blunting of GH release, insulin-like growth factor I (IGF-I) bioactivity, and collagen synthesis
- So if he is taking glucocorticoid administer recombinant IGF-1 (not much reduced)
What will happen if we add androgens, estrogens, thyroid hormone, or anabolic steroids to the regimen?
They might accelerate the epiphysial closure and compromise the final height
Which drug should we use for GH preparation?
1) Recombinant somatropin
2) Somapacitan
3) Lonapeg somatropin
Which drug should we use in case of hypothalamic damage that leads to reduced GH levels?
Sermorelin
Which drug should we use in case of IGF-1 deficiency?
Mecasermin
What are the different GHIH analogs?
1) Octreotide subcutaneous
2) Octreotide IM
3) Octreotide Oral
4) Pasireotide
5) Lanreotide
What is octreotide used for?
1) Acromegaly
2) Carcinoid syndrome
3) Pituitary adenomas that secrete thyrotropin
4) Tumors that produce vasoactive intestinal polypeptide
What is the usual administration of octreotide?
Mainly Subcutaneously (every 8 hours), and there is a long-acting IM formulation (Sandostatin LAR, once a month), an oral formulation is also available (Mycapssa)
