Octreotide

Publisher Website
Google Scholar
Abstract
Octreotide is an analogue of somatostatin. Like endogenous somatostatin, it exerts a potent inhibitory effect on the release of anterior pituitary growth hormone and thyroid-stimulating hormone, and peptides of the gastroenteropancreatic endocrine system, while overcoming some of the shortcomings of exogenously administered somatostatin, namely a short duration of action, a need for intravenous administration and postinfusion rebound hypersecretion of hormone. Clinical studies have shown that octreotide is effective in the treatment of acromegaly and thyrotrophinomas. In comparative trials octreotide was significantly superior to bromocriptine in patients with acromegaly. Octreotide also appears to provide a significant advantage over existing therapies in the management of the carcinoid syndrome and offers considerable therapeutic potential in reversing carcinoid crises which may be life- threatening. Trials in patients with tumours producing vasoactive intestinal peptide demonstrated that octreotide may be an effective first-line choice for this condition, which has usually metastasised and become refractory to traditional symptomatic therapy. In limited studies in patients with high-output secretory diarrhoea, including cryptosporidium-related diarrhoea associated with AIDS and in patients with small bowel fistulas, octreotide has been shown to be effective in reducing stool/fistula output. However, well-designed clinical trials are still required to confirm its long term usefulness in these disorders. Similarly, although the use of octreotide in other conditions such as neonatal hypoglycaemia caused by nesidioblastosis, reactive pancreatitis, insulin- dependent diabetes mellitus, postprandial hypotension and the dumping syndrome has provided encouraging preliminary results, more studies are needed to clarify the place of octreotide in their treatment. Overall, octreotide appears to be well tolerated with the most frequently reported reactions being pain at the site of injection and gastrointestinal symptoms such as abdominal cramps, nausea, bloating, flatulence, diarrhoea and steatorrhoea. These adverse effects usually abate with time. Additionally, octreotide, like endogenous somatostatin, may also result in cholelithiasis, presumably by altering fat absorption and possibly by decreasing motility of the gallbladder. Thus, octreotide represents a new departure from traditional therapies in the treatment of various pathophysiological states associated with excessive peptide production and secretion. It offers a significant advantage over existing therapies in the medical management of patients with acromegaly, thyrotrophinomas, the carcinoid syndrome, tumours producing vasoactive intestinal peptide and severe secretory diarrhoea in whom conventional management options have either become exhausted or have provided suboptimal symptomatic relief. Octreotide is a long acting synthetic octapeptide analogue of naturally occurring somatostatin which suppresses secretion of anterior pituitary growth hormone and thyroid-stimulating hormone, in addition to a wide variety of peptide hormones from the gastroenteropancreatic endocrine system. Glucagon, gastric inhibitory, peptide, pancreatic polypeptide and motilin are the most sensitive to the inhibitory action of octreotide while gastrin is the least affected. Various animal models have demonstrated that octreotide is highly resistant to enzymatic degradation and that it selectively inhibits growth hormone secretion more powerfully than it does insulin secretion. In healthy subjects octreotide produces a mild transient postprandial hyperglycaemic action, probably related to the postprandial suppression of insulin release. This suppression appears to override the other actions of octreotide (namely glucagon suppression and delayed nutrient absorption) which would tend to improve glucose tolerance. Results from studies in patients with acromegaly generally confirm the effects of octreotide on growth hormone secretion in normal volunteers, with octreotide producing a potent and prolonged inhibitory effect. Octreotide 50µg appears to provide maximal inhibition although there is evidence that a higher dose (100µg) causes a prolongation of the period of inhibition. Additionally, no rebound hypersecretion of growth hormone is observed when the suppressive effect of octreotide has worn off. Single-dose studies comparing the growth hormone-inhibitory effects of octreotide and bromocriptine in patients with acromegaly clearly demonstrate significantly greater growth hormone-lowering activity for octreotide. Moreover, the combination of these 2 agents significantly inhibited growth hormone release in patients not responding to either drug administered separately. Octreotide produces a clear symptomatic improvement in flushing episodes and diarrhoea with a concomitant significant reduction in serotonin levels in patients with carcinoid tumours. Furthermore, the reduction in urinary excretion of 5-hydroxyindole acetic acid (a metabolite of serotonin) in such patients following octreotide administration appears to be dose related. Significant octreotide-induced suppression of postprandial pancreatic polypeptide, gastric inhibitory peptide and insulin release confirm earlier findings reported in healthy volunteers. Administration of octreotide to patients with vasoactive intestinal peptide-producing tumours rapidly controls secretory diarrhoea and causes a marked reduction in mean plasma vasoactive intestinal peptide levels, although these values still remains well above the upper limit of normal. This discrepancy between symptomatic relief and hormone response may be explained by the presence of larger, possibly less biologically active, forms of circulating vasoactive intestinal peptide during octreotide therapy. Results from intestinal perfusion studies suggest that the octreotide-induced increases in fluid and electrolyte absorption from the...