What is the mechanism of action (MOA) of Octreotide (somatostatin analog)?

Mechanism of Action of Octreotide

Octreotide exerts pharmacologic actions similar to the natural hormone somatostatin but is more potent, binding principally to somatostatin receptor subtypes 2 and 5 to inhibit the release of various peptide hormones in the gut, pancreas, and pituitary. 1

Primary Mechanisms

Octreotide functions through several key mechanisms:

• Hormone Inhibition: Acts as a potent inhibitor of:

  • Growth hormone (GH)
  • Glucagon
  • Insulin
  • Thyroid-stimulating hormone (TSH)
  • Luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) 1

• Gastrointestinal Effects: Inhibits release of multiple gut peptides:

  • Serotonin
  • Gastrin
  • Vasoactive intestinal peptide (VIP)
  • Secretin
  • Motilin
  • Pancreatic polypeptide 1

• Vascular Effects: Decreases splanchnic blood flow 1

• Anti-proliferative Effects: At high dosages, octreotide can:

  • Antagonize growth factor effects on tumor cells
  • Potentially induce apoptosis 2

Receptor Binding Profile

Octreotide has selective affinity for specific somatostatin receptor subtypes:

• Binds with high affinity to SSTR subtype 2
• Binds with lower affinity to SSTR subtype 5 2
• This receptor selectivity explains why octreotide is effective in certain conditions but not others

Pharmacokinetic Advantages

Unlike natural somatostatin (half-life of 1-3 minutes), octreotide has:

• Longer elimination half-life of 1.7-1.9 hours
• Duration of action extending up to 12 hours depending on tumor type
• Complete and rapid absorption following subcutaneous injection 1

Clinical Applications Based on MOA

The mechanism of action explains octreotide's effectiveness in:

1. Neuroendocrine Tumors:

   • Carcinoid syndrome: Controls flushing and diarrhea by inhibiting serotonin and other peptides
   • VIPomas: Treats watery diarrhea by inhibiting VIP release 2

2. Acromegaly:

   • Substantially reduces GH and/or IGF-1 levels 1
   • May also induce insulin-like growth factor-binding protein-1 (IGFBP-1) independently of GH and insulin, providing an additional mechanism for attenuating the GH-IGF-I axis 3

3. Other Endocrine Conditions:

   • Glucagonomas: Improves symptoms by inhibiting glucagon release
   • Less effective in insulinomas due to lower SSTR2 expression (only present in about 50% of cases) 2

Important Clinical Considerations

• Receptor Presence: Effectiveness depends on the presence of somatostatin receptors:

  • Present in 70-95% of neuroendocrine tumors
  • Only in about 50-60% of insulinomas
  • Less evident in poorly differentiated NETs and somatostatinomas 2

• Dose-Response Relationship: Biochemical response rates (inhibition of hormone production) are seen in 30-70% of patients with symptomatic control in the majority of patients 2

• Potential Side Effects: Related to its mechanism of action:

  • Gallstone formation (inhibits gallbladder contractility)
  • Fat malabsorption
  • Vitamin A and D malabsorption
  • Altered glucose metabolism (both hypo- and hyperglycemia) 2, 1

Understanding octreotide's mechanism of action is crucial for optimizing its use in various clinical scenarios and anticipating potential adverse effects based on its physiological impacts.