Ant pituitary hormone drugs pharmacology

1. Drugs related to Ant Pituitary
hormones
Dr KG Bandekar
MD Pharmacology

2. Hormone
• Substances of intense biological activity
produced by specific cells (Endocrine glands)
and act away from their site of production
through circulation

3. Role of hypothalamus
• Secretion of pituitary hormones is controlled
by the hypothalamus through releasing and
release inhibitory hormones

4. HP axis
Hypothalamus
GHRH Stomatostatin
Ant Pituitary
GH
Increase GH
secretion
Decreased
Secretion

5. Ant Pituitary Hormones
Sr no Hormones Controlling Hormones
1 Growth Hormone (GH) i) GH releasing Hormone (GHRH)
ii) GH release inhibiting hormone
(Somatostatin)
2 Adrenocorticotropic hormone (ACTH) Corticotropin releasing hormone
(CRH)
3 Thyroid stimulating hormone (TSH) TRH
4 Gonadodropins (Gn)
a) Follicle stimulating Hormone (FSH)
b) Leutinising hormone (LH)
GnRH
5 Prolactin Prolactin Inhibitory hormone (PRIH)

6. Therapeutic use
Therapeutically used Ant Pit Hormones (& drugs
rel to these hormones):
• GH
• Gonadotropins (Gns)
• Prolactin
(Diagnostic value : TSH and ACTH)

7. GH and related drugs

8. HP axis
Hypothalamus
GHRH Stomatostatin
Ant Pituitary
GH
Increase GH
secretion
Decreased
Secretion

9. PD
• GH mediates its effects via cell surface
receptors of the JAK/STAT cytokine receptor
superfamily
…MCQ

10. Effects of GH on carbohydrate,
protein and fat metabolism

11. Effect On Carbohydrate metabolism
Blood glucose level increases :
1. Uptake of glucose by muscles is reduced
2. Output from liver is increased
It promotes utilization of fat and spares
carbohydrates
GH accentuates the metabolic derangement in
diabetes

12. Insulin like Growth Factor -1(IGF-1)
• The growth-promoting effects of GH are
mediated mainly, but not solely, through IGF-I
(Somatomedins).
• Most Circulating IGF-I is produced by liver.

13. IGF-1
• GH and IGF-I have opposite effects on insulin
sensitivity.
• GH reduces insulin sensitivity, which results in
mild hyperinsulinemia and increased blood
glucose levels
• IGF-I has insulin-like effects on glucose
transport

14. Effect On Protein metabolism
Positive nitrogen balance
1. Increased uptake of amino acids by tissues
2. Protein synthesis
3. Promotes retention of nitrogen
4. More protoplasm is formed

15. Effect on fat metabolism
• Induces lipolysis in adipose tissue

16. Clinical Uses GH
Ref : Kadzung

17. GH related drugs
1. Recombinant GH
2. recombinant GHRH analogs
3. Somatostatin rel drugs
4. Mecasermin : a complex of recombinant
human IGF-1 and IGF-binding protein-3
5. Pegvisomant is a GH receptor antagonist

18. 1. Recombinant GH
• Somatrem
• Somatropin

19. 2. recombinant GHRH analogs
• Sermorelin
• Hexarelin
**Fundoscopic examination of children is
recommended periodic intervals (because,
rarely GH therapy is associated with
intracranial hypertension with papilloedema,
visual changes).
Ref: Kadzung

20. 3. Somatostatin analogs
• Octreotide
• Vapreotide
• pasireotide
• seglitide

21. ???
• Somatomedin
• Somatostatin
• Somatropin
• Sermorelin

22. Mecasermin : a complex of
recombinant human IGF-1 and IGF-
binding protein-3
• Indication: Growth failure due to defi of IGF-1
that is not responsive to GH.
• Route: Subcutaneous
• IGF-binding protein-3: to maintain adequate
half-life of IGF-1.
• ADR: hypoglycemia

23. Pegvisomant : GH receptor antagonist
• Pegylated: Poly ethylene glycol….improves
absorption
• Indication: GH secreting Pit tumors

24. Gn, GnRH & and rel drugs

25. Gn
FSH
• Spermatogenesis
• Estrogen secretion
LH
• Progesterone
• Testosterone
Secretion of Gn is controlled by GnRH that is secreted
from the hypothalamus in a pulsatile manner.
GnRH = FSHIL/1-RH or simply LHRH or Gonadorelin.
To remember……….FSH …S ….Spermatogenesis , Strogen

26. Receptors
• LH & FSH rec are GPCR
MCQ

27. hCG
• Secreted by placenta
• Fn = To maintain corpus luteum in preg
• Binds to LH receptors
• Action is = that of LH
…..Clinical imp in Male Hypogonadotropic
hypogonadism
Testestorone secretion

28. Polycystic ovarian disease
(PCOD)
• Androgen levels high
• High LH
(LH…. Testosterone)
• LH / FSH level is high
• Rational in Rx ….. Increase FSH level
FSH preparations given

29. Preparations of Gn
A. Purified preparations obtained from human
source… Urine samples
B. Recombinant preparations

30. A. Purified preparations
i. Menotropins (FSH + LH) = obtained from
Urine of menopausal women
ii. Urofollitropin = Menotropin (pure FSH)
iii. Human chorionic gonadotropin (hCG)

31. B. Recombinant preparations
i. Recombinant human FSH (rh FSH) =
Follitropin alpha, follitropin beta
ii. Rcombinant human LH (rhLH) = Lutropin…
(withdrawn from market)
iii. Recombinant hCG

32. ADRs
• Ovarian hyper stimulation syndrome
• Multiple preg
• Allergic reactions

33. GnRH
• Imp…..
• If given pulsatile manner… FSH/ LH secretion
• Sustained continuous administration….
Inhibition
• Cannot be used in Rx hypogonadism (which
req continuous Rx)

34. GnRH rel drugs
A. GnRH analogs
B. GnRH antagonists

35. GnRH analogs = superactive
agonists
• Goserelin
• Nafarelin
• Triptorelin
• Leuprolide
Relin….

36. Natural GnRH vs analogs
• ~ 100 times more potent
• Longer acting
• High affinity for GnRH receptors
• No enzymatic degradation
than natural
GnRH

37. Nafarelin
• Intra nasal spray but still ‘F’ is ~5%….MCQ /
viva

38. Uses: Nafarelin
1. Assisted Reproduction: to suppress endogenous
LH surge when controlled ovarian stimulation is
done by exogenous FSH & LH…. Precisely timed
mature oocytes can be harvested
2. Uterine Fibroids:
3. Endometriosis : (endometrial tissue at other
site)
4. Precocious puberty: Rx till 12 yrs.. Reversible
after stopping

39. Goserelin
• i.m Depot preparation…. Long acting
• Use
–Ca prostate…. { for initial 3-4 weeks
bicalutamide / flutamide (androgen
antagonist) is given…. Increased androgen
production due to increased Gn initially}…..
Viva qn
–Endometriosis

40. GnRH analogs contd..
• Triptorelin
• Leuprolide

41. GnRH rel drugs
A. GnRH analogs
B. GnRH antagonists

42. GnRH antagonists
• Ganirelix
• Cetrorelix
• Degarelix

43. Adv over long acting GnRH agonists
1. Quick Gn suppression
2. Complete Gn suppression
3. Lower risk of ovarian hypersensitivity
syndrome
Viva qn…

44. Use : GnRH antagonists
• Controlled ovarian stimmulation ( in vitro
fertilization)… inhibit LH surge

45. Prolactin & rel drugs

46. Prolactin Rel drugs
Prolactin / agonist
• No clinical use
Prolactin inhibitors
• Bromocriptine
• Cabergolin

47. Bromocriptine
• Synthetic Ergot
• D2 agonist
• Uses:
1. Hyperprolactinaemia
2. Parkinsonism
3. Acromegally
4. Type 2 DM

48. Cabergolin
• D2 agonist (selective to pituitary D2 rec)
• Long acting
• Drug of choice in Hyperprolactinaemia ….. MCQ

49. Thank you!