Somatostatin gastrointestinal

Use of the first-generation somatostatin analog octreotide is limited by its extremely short duration of action and requirement for subcutaneous administration at least three times a day. If a patient s GH level returns to baseline before the end of an 8-hour dosing interval, the frequency of octreotide administration can be increased to every 4 to 6 hours. Most patients require octreotide in doses of 100 to 200 meg three times daily.19,20 To improve patient tolerance to gastrointestinal (GI) adverse effects, start octreotide at 50 meg every 8 hours.20 Assess IGF-I serum concentrations every 2 weeks after initiating therapy to further titrate dose in increments of 50 meg per dose. 

C. Carcinoid tumors arise from neuroendocrine cells of the gut and secrete serotonin and gastrointestinal hormones, which activate the gastrointestinal tract and result in diarrhea. Most of these tumors have receptors for somatostatin, which inhibit secretion when activated, resulting in reduced activity of the gut. Octreotide is a stable analogue of... 

Somatostatin, a 14-amino-acid peptide (Figure 37-2), is found in the hypothalamus, other parts of the central nervous system, the pancreas, and other sites in the gastrointestinal tract. It inhibits the release of GH, glucagon, insulin, and gastrin. 

Somatostatin is a 14-amino-acid peptide that is released in the gastrointestinal tract and pancreas from paracrine cells, D cells, and enteric nerves as well as from the hypothalamus (see Chapter 37). Somatostatin is a key regulatory peptide that has many physiologic effects ... 

One of the surprising findings of recent brain and central nervous system research is that chemical substances previously considered to be exclusive to ihe province of the brain have been found in organs outside the nervous system (e.g., somatostatin, neurotensin, and enkephalins have been found in the gut), and conversely, that other substances active in other organs, but not previously associated with the central nervous system, have been found in the latter (e.g.. gastrin, vasoactive intestinal polypeptide (VIP), and choiecystokinin. traditionally associated with the gastrointestinal tract, but now found in the central nervous system). 

Somatostatin (SST) 35, a cyclic tetradecapeptide disulfide, was isolated in 1973 by Guillemin from hypothalami. SST has a broad profile of endocrine and gastrointestinal... 

I. Somatostatin Receptor Agonists Treatment of Excess Gastrointestinal Secretion... 

The somatostatin analogue, D-Phe-c(Cys-Tyr(I)-D-Trp-Lys-Val-Cys)-Thr-NH2 containing a Tyr phenyl ring iodinated in the 3- or 5-position was prepared by Gordon (1) and was effective in inhibitory excess pituitary, pancreas, and gastrointestinal tract secretions. 

Transient gastrointestinal symptoms (nausea, diarrhea, abdominal discomfort, and flatulence) occur in up to 50% of patients during the first few days of treatment, but usually resolve spontaneously after the first 1-2 weeks of treatment (13,18). Nausea and vomiting occur in up to 25% of patients after somatostatin and are also common... 

Cells throughout the gastrointestinal tract release somatostatin. Somatostatin inhibits acid secretion in the stomach and it promotes absorption of sodium, chloride and water in the small intestine and colon (Krejs 1986). The somatostatin analogs octreotide and lanreotide have been shown to decrease intestinal secretion in animal models (Botella et al 1993) and in humans with specific metabolic intestinal secretory disorders however, these drugs are not used widely in human medicine. In one study in horses, octreotide was shown to decrease gastric acidity (Sojka et al 1992) but its effects on intestinal or colonic secretion in horses have not been reported. 

There is a formidable array of polypeptide hormones of the gastrointestinal tract that includes secretin, pancreo-zymin-cholecy.stokinin. gastrin, motilin. neurotensin, vasoactive intestinal peptide, somatostatin, and others. The biosynthesis. chemistry, secretion, and actions of these hormones have been reviewed. ... 

---