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Y2S1-Pharmacology > Growth hormone agonist and antagonists > Flashcards

Growth hormone agonist and antagonists Flashcards

1
Q

What are the routes of administration of GH drugs?

A

1) Subcutaneous

2) Intramuscular

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2
Q

What are the six hormones that are secreted by the adenohypophysis?

A

1) Corticotropin (adrenocorticotropic hormone (ACTH))

2) Somatotropin (growth hormone)

3) Follicle-stimulating hormone (FSH)

4) Leutinizing hormone (LH)

5) Thyrotropin (TSH)

6) Prolactin

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3
Q

What are the hormones that are secreted by the hypothalamus?

A

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])

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4
Q

Other than GH, what does somatostatin inhibit?

A

Digestion and TSH

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5
Q

What are the actions of growth hormones?

A
  • 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
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6
Q

What are the growth hormone preparations?

A
  • 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

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7
Q

What are the different GH replacement drugs we have?

A

1) Recombinant somatotropin (once daily)

2) Somapacitan (once weekly for adults)

3) Lonapegsomatropin (once weekly for kids)

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8
Q

What are the recombinant forms of IGF-1?

A

Mecasermin

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9
Q

What is mecasermin?

A
  • 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
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10
Q

When is mecasermin used?

A
  • Normal GH levels but:

1) Mutated receptor (laron syndrome)

2) Patient develops antibodies against GH

3) GH is unable to release IGF-1

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11
Q

What is the side effect of mecasermin?

A

Hypoglycemia

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12
Q

Which drug is indicated for children with severe IGF-1 deficiency, growth hormone receptor mutation, and neutralizing antibodies to GH?

A

IGF-1

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13
Q

What is Sermorelin?

A
  • 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
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14
Q

Which drug is used for idiopathic GH deficiency?

A

Sermorelin

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15
Q

Which drug is a recombinant of GHRH?

A

Sermorelin

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16
Q

Which drug is used due to GH from hypothalamic damage?

A

Sermorelin

17
Q

What is the effect of glucocorticoids on the growth-promoting effects of recombinant GH?

A

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)
18
Q

What will happen if we add androgens, estrogens, thyroid hormone, or anabolic steroids to the regimen?

A

They might accelerate the epiphysial closure and compromise the final height

19
Q

Which drug should we use for GH preparation?

A

1) Recombinant somatropin

2) Somapacitan

3) Lonapeg somatropin

20
Q

Which drug should we use in case of hypothalamic damage that leads to reduced GH levels?

A

Sermorelin

21
Q

Which drug should we use in case of IGF-1 deficiency?

A

Mecasermin

22
Q

What are the different GHIH analogs?

A

1) Octreotide subcutaneous

2) Octreotide IM

3) Octreotide Oral

4) Pasireotide

5) Lanreotide

23
Q

What is octreotide used for?

A

1) Acromegaly

2) Carcinoid syndrome

3) Pituitary adenomas that secrete thyrotropin

4) Tumors that produce vasoactive intestinal polypeptide

24
Q

What is the usual administration of octreotide?

A

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)

25
Q

What is lanreotide acetate?

A
  • It is a prolonged formulation of cyclic octapeptide analog of somatostatin
26
Q

How is lanreotide acetate administered?

A

Subcutaneously

27
Q

What is Pasireotide?

A

Somatostatin analog drug that has a higher affinity for its receptors more than the other octreotide and lanreotide, leading to a greater inhibition of GH

28
Q

When is pasireotide used?

A

In octreotide and lanreotide-resistant adenomas

29
Q

What is the major side effect of somatostatin analog drugs?

A

Sometimes they inhibit the gallbladder contractility and decrease the secretion of bile, developing a biliary sludge and asymptomatic gallstones (cholelithiasis, typically occurs in patients treated for more than 12 months)

30
Q

What are the side effects of GHIH analog?

A
  • GHIH

1) G: GI Adverse effects (cholelithiasis)

2) H: Heart abnormalities (Sinus bradycardia, conduction abnormalities, and arrhythmias have been reported with octreotide and lanreotide)

3) I: Insulin (hyper/hypoglycemia, by altering the balance of regulatory hormones)

4) H: Hypothyroidism (suppresses the release of TSH)

31
Q

Which drug is used in acromegaly with patients with increased GH, IGF, and prolactin?

A

Cabergoline (Dopamine agonist),D2 receptor agonist

32
Q

What are the parameters that we should monitor when administering cabergoline?

A

1) Visual disturbance

2) Menstrual cycles

3) Sexual function (in men)

4) Prolactin serum concentration (every 3-4 weeks)

33
Q

What is Pegvisomant?

A
  • A GH receptor antagonist that reduces the serum level of IGF-1 in patients with acromegaly, it mainly blocks the GH receptors in the liver

bkafi-somatotropin (hahahaha)

34
Q

What are the drugs used for dwarfism?

A

1) GH replacement

  • Recombinant somatotropin
  • Somapacitan (for adults)
  • Lonapegsomatropin (for kids)
  • Concomitant administration of androgens, estrogens, thyroid hormones, anabolic steroids, or Glucocorticoids with the above drugs is not recommended
  • Glucocorticoids may inhibit the growth-promoting effects of recombinant GH

2) Recombinant IGF-1

  • Mecasermin (causes hypoglycemia)

3) Hypothalamic issue (low GHRH)

  • Sermorelin (subcutaneous)
35
Q

What are the drugs used for gigantism?

A

1) GHIH analogue

1a) Octreotide subcutaneous

1b) Octreotide IM (every month)

1c) Octreotide Oral

1d) Pasireotide (subcutaneous, broader the affinity of the GHIH receptor)

1e) Lanreotide (prolonged formulation, once a month subcutaneously)

2) Cabergoline (D2 agonist, it also work for hyperprolactinemia and acromegaly)

3) Pegvisomant (GH receptor antagonist, inhibits IGF-1 secretion)

36
Q

What are the non-pharmacological treatment of acromegaly?

A

1) Transsphenoidal surgical resection of the GH-secreting adenoma

2) Radiation therapy

37
Q

Which drug is used in patients with excess GH that have a whole/partial resistance to octreotide?

A

Pegvisomant

Y2S1-Pharmacology (10 decks)

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