Somatostatin analogues

Somatostatin analogues

F.Sarvghadi MD

Research Institute for Endocrine sciences

Shahid Beheshti University

of Medical Sciences

     Agenda:

• Introduction.
• Pharmacokinetics
• Effects on Clinical Features
• Predictors of response
• Indication for usage
• Primary  vs. secondary efficacy trials
• Side effects
• New SRLs
• Adverse effects
• Conclusion

Introduction:

• Somatotropin release-inhibiting hormone (SRIF) or somatostatin 14 was discovered in 1973. Somatostatin (SRIF) is a cyclic peptide, includes SRIF-14 and SRIF-28.
• SRIF14 is the predominant peptide in the brain, while SRIF28 is the predominant peptide in the GI tract.
• The name somatostatin was given as this peptide was primarily discovered to inhibit pituitary GH release, however, this peptide also inhibits TSH, ACTH and other central and peripheral hormones.
• Hypothalamic somatostatin is produced predominantly in the anterior periventricular nucleus, as well as in the paraventricular, arcuate and ventromedial hypothalamic nuclei.
• The primary function of somatostatin is to inhibit pituitary hormone secretion and, to a lesser extent, pituitary cell growth.
• In the hypothalamus, somatostatin inhibits release of several hypothalamic hormones and neurotransmitters, including CRH, TRH, dopamine, norepinephrine and GHRH , also inhibits its own secretion from the periventricular nucleus.
•  In the pituitary, somatostatin inhibits secretion of GH, TSH and ACTH in the presence of low glucocorticoid levels.

• Somatostatin actions usually are inhibitory:

• Somatostatin also inhibits secretion of insulin, glucagon, and PP in the endocrine pancreas.
• In the gastrointestinal tract:

      Somatostatin inhibits pancreatic exocrine secretion and

      gastric acid secretion.

• In the brain, somatostatin regulates metabolism of amyloid-β peptide, a primary pathogenic agent of Alzheimer’s disease.
• Somatostatin signals through five somatostatin receptor subtypes, SSTR1, 2, 3, 4 and 5. The SSTR2 and SSTR5 subtypes are preferentially expressed on somatotroph and thyrotroph cell surfaces .
• Somatostatin 14 exhibits high binding affinities to all the receptor subtypes, but has greatest affinity to SSTR2, which is the subtype largely responsible for inhibiting pituitary hormone secretion.
• The inhibitory properties of somatostatin make it suitable

     for the treatment of conditions characterized by excess

     hormone secretion or GI disorders:

     Neuroendocrine tumors.

     Acromegaly.

     Cushing syn.

     Portal hypertension .

     Gastrointestinal bleeding.