Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 35-year-old man presenting with severe watery diarrhea was diagnosed as having the watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome with the elevation of plasma vasoactive intestinal peptide (VIP) level. Imaging diagnostic techniques revealed a hypervascular tumor at the tail of the pancreas as well as a solitary liver metastasis. During the patient's stay in hospital, he developed acute renal failure probably due to persistent dehydration and severe hypokalemia. Although these complications improved with artificial dialyses, severe watery diarrhea continued, which made it difficult to achieve surgical resection of the tumor. A new long-acting and potent somatostatin analogue, SMS 201-995 (Sandoz Ltd, Basel, Switzerland), was tested and was shown to be effective; after a few hours of subcutaneous injection of this agent, the watery diarrhea disappeared, which in turn improved the patient's hypokalemia, hypercalcemia and metabolic acidosis. Three weeks later, distal pancreatectomy with splenectomy and hepatic lobectomy were successfully performed, and the patient resumed his normal life. The somatostatin analogue has been reported to be useful in the long-term treatment of patients with inoperable WDHA syndrome. The present case demonstrated that short-term administration of this agent is also useful for improving the condition of WDHA patients at the preoperative stage.
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PMID:A case of the watery diarrhea-hypokalemia-achlorhydria syndrome: successful preoperative treatment of watery diarrhea with a somatostatin analogue. 255 28

In a 60-year-old woman with an inoperable vipoma, satisfactory improvement of severe watery diarrhea was obtained over a 12-month period by subcutaneous administration of the somatostatin analogue SMS 201-995. It is suggested that SMS 201-995 may be useful in such inoperable cases, or when surgery would carry a high risk.
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PMID:The somatostatin analogue SMS 201-995 in long-term treatment of vipoma. Case report. 255 17

Octreotide is a long-acting cyclic octapeptide with pharmacologic actions mimicking those of the natural hormone somatostatin. It can suppress the secretion of serotonin, as well as the gastroenteropancreatic peptides gastrin, vasoactive intestinal peptide (VIP), insulin, glucagon, secretin, motilin, and pancreatic polypeptide. It also suppresses growth hormone and decreases splanchnic blood flow. Octreotide is completely and rapidly absorbed following subcutaneous injection and has an elimination half-life of 1.5 hours. Clinical trials reviewed here show octreotide useful in the treatment of diarrhea associated with VIP secreting tumors, as well as diarrhea and flushing associated with carcinoid syndrome, both conditions for which the drug is approved. Clinical trials involving the use of octreotide in the treatment of acromegaly are also reviewed. Adverse reactions to octreotide are mild to moderate and most commonly involve injection site pain and diarrhea. Drug interactions are apparently related to the drug's pharmacologic effects. Octreotide is given subcutaneously two to three times daily, with daily doses ranging from 50mcg to 1,500mcg per day. Further research appears necessary to clarify dosing issues.
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PMID:Debut of a somatostatin analog: octreotide in review. 255 39

Five patients with external pancreatic fistulas were treated with a synthetic peptide that mimics the action of somatostatin (Sandostatin, Sandoz; East Hanover, NJ). Four of the patients developed fistulas after drainage of pancreatic pseudocysts and one developed a fistula following resection of a pancreatic carcinoid. One day after initiation of therapy, the mean fistula output for the group decreased by 52 per cent. By three days, fistula output decreased by 70 per cent. All fistulas closed in 7 to 44 days. Adverse reactions to the drug included diarrhea in one patient and transient hyperglycemia in another. Sandostatin is effective in decreasing drainage from external pancreatic fistulas and may, therefore, facilitate their closure. No serious adverse reactions to the drug were noted. Further studies will better define the role of Sandostatin in the treatment of pancreatic fistulas.
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PMID:Treatment of external pancreatic fistulas with somatostatin. Second place winner: Conrad Jobst award. 257 57

A retrospective study of 224 patients with medullary thyroid carcinoma (MTC) diagnosed between 1963 and 1988 was performed to 1) establish the diagnosis of MTC in early childhood, 2) establish the role of prophylactic regional lymphadenectomy in patients with MTC, 3) study the effect of chemotherapy on MTC patients with metastatic disease, 4) study the effect of somatostatin analog 201-995 (Sandoz Pharmaceuticals) on the frequency of diarrhea in MTC, and 5) locate the common region(s) of gene deletion on chromosome 1 and examine the loss of heterozygosity on chromosome 10 in tumors. Our data indicated that a progressive rise of serum calcitonin in early childhood (rather than the expected fall with age seen in normal subjects) is diagnostic of MTC. No differences in clinical course of prognosis were observed between patients with MTC localized to the thyroid who had prophylactic neck node dissection and those who did not. Conventional chemotherapy had no significant benefit in the treatment of patients with metastatic disease. The somatostatin analog was found to be an effective drug in the treatment of diarrhea associated with MTC. Allelic losses were frequently found in MTCs and pheochromocytomas, and the loss of DNA sequences in these tumors appeared to involve the distal third of the short arm of chromosome 1, with a common breakpoint at 1p32.
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PMID:Diagnosis, management, and pathogenetic studies in medullary thyroid carcinoma syndrome. 257 46

Recent studies have suggested that somatostatin could reduce calcitonin plasma levels (CT) in normal subjects and in medullary thyroid carcinoma (MTC). The aim of this study was to examine the usefulness of the somatostatin analog, sandostatine (SMS 201.995) in MTC with elevated residual CT levels post-thyroidectomy with or without metastases. 18 patients (17-64 years, 12 men and 8 women) with CT greater than 850 pg/ml (N less than 150 pg/ml) and with metastases in 12 cases, were studied. MTC was sporadic in 11 cases, familial in 4 cases and of undefined form in 3. Initial posology was 300 micrograms/d of sandostatin (3 injections/day). It was then increased by 300 micrograms/d every 9 day till a maximum of 1500 micrograms/d. Treatment duration was 37 days in 11 cases and 60 days in 7 cases. Plasma CT and carcinoembryonic antigen levels (CEA) were measured before treatment and at the end of each dosage plateau. Morphologic evaluation of metastases was done at 0, 30, 60 days. 7/18 patients were reevaluated 2 to 8 months after with drawal of sandostatine. Treatment was well tolerated. Flushes improved in 4 out of 5 cases but diarrhea in only 2 out of 9 patients. Sandostatine was without any effect on plasma CEA. Heterogenous responses were observed for plasma CT levels (CT decreases greater than 20% in 8/18 patients when 900 to 1500 micrograms/day were administered). Patients were subdivised into 3 groups according to CEA levels and presence or absence of metastases. Group A (n = 9) had elevated CEA levels (greater than 10 mg/ml) and metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of subcutaneous administration of sandostatine (SMS 201.995) in 18 cases of thyroid medullary cancer]. 263 43

In this study, the pharmacokinetics, efficacy, and tolerability of 25 and 100 micrograms of octreotide given t.i.d. for 7 days subcutaneously were investigated in 12 healthy male subjects. Serum concentrations of the drug were well reproducible within 1 wk. Octreotide significantly raised 24-h median intragastric pH on day 1, but no longer on day 6. Peptone-stimulated gastric acid and volume secretion were markedly less suppressed by octreotide on day 7 compared with day 2. Peptone-stimulated gastrin release was abolished on days 2 and 7, as was peptone-stimulated insulin release. Blood glucose was altered in a biphasic pattern on days 2 and 7. All effects of octreotide were without clear-cut dose-response relationship. A mean half-life of 115 min was calculated. Dose-unrelated side effects (e.g., abdominal cramps, diarrhea, and fatty stools) were registered. In conclusion, octreotide is a powerful inhibitor of gastric acid and volume secretion during acute treatment. Its loss of efficacy during a 1-wk administration may be due to the adaptation of somatostatin receptors and hormonal counterregulation.
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PMID:Diminishing efficacy of octreotide (SMS 201-995) on gastric functions of healthy subjects during one-week administration. 264 51

The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects and drug interactions, dosage, availability and cost, and indications for use of octreotide, a new synthetic analogue of the peptide hormone somatostatin (SS), are reviewed. Like SS, octreotide suppresses secretion of pituitary growth hormone (GH) and thyrotropin and decreases release of a variety of pancreatic islet cell hormones including insulin, glucagon, and vasoactive intestinal peptide (VIP). Octreotide also reduces splanchnic blood flow, gastric acid secretion, GI motility, and pancreatic exocrine function and alters the absorption of water, electrolytes, and nutrients from the GI tract. The elimination half-life of i.v. octreotide is 72-98 minutes, compared with 2-3 minutes for i.v. SS. Usual administration of octreotide is by the i.v. or s.c. route. Octreotide has been studied in the treatment of hormone-secreting pituitary tumors and pancreatic islet cell tumors. Octreotide therapy lowers GH secretion and improves clinical symptoms in patients with acromegaly and may suppress clinical symptoms to a greater degree than bromocriptine. Patients with carcinoid syndrome and VIP-secreting tumors (vipomas) have had substantial improvement in clinical symptoms with administration of octreotide. This agent does not appear to be effective in the treatment of nonvariceal upper GI bleeding and acute pancreatitis; its relative usefulness in the treatment of variceal bleeding is not established. Adverse effects associated with octreotide therapy generally have been mild, including pain or burning at the injection site, abdominal pain, and diarrhea. Octreotide has been shown to interfere with absorption of oral cyclosporine. Standard initial therapy is octreotide acetate 50-100 micrograms s.c. every 8-12 hours, with titration based on clinical and biochemical effects. Up to 3000 micrograms/day of octreotide acetate has been administered to patients with acromegaly without serious adverse effect. Octreotide is marketed under the brand name Sandostatin and is available in 1-mL ampuls containing 50, 100, and 500 micrograms of octreotide acetate. Because the conditions for which octreotide appears to be most effective are uncommon, the drug should be considered for addition to the formulary in tertiary-care institutions only; addition of octreotide to the formulary of a community hospital is probably unnecessary. The synthetic analogue octreotide is longer acting and more specific in pharmacologic action than SS.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Octreotide, a new somatostatin analogue. 265 11

We evaluated the effectiveness of a more potent and longer-acting somatostatin analogue (SMS 201-995) as an adjunct to insulin therapy, in a double-blind placebo-controlled randomized study of 26 C-peptide-negative type I (insulin-dependent) diabetic patients (20 women, 6 men, aged 22-40 yr) on their conventional drug regimens for 12 wk. Eight patients received a low dose (10 micrograms) of the analogue, 9 received a high dose (50 micrograms) of the analogue, and 9 received placebo subcutaneously before breakfast and dinner. Twenty-four-hour serum glucose, free insulin, plasma growth hormone (GH), and glucagon profiles were obtained before and during treatment at 4-wk intervals. The mean age, duration of diabetes, daily insulin dose, and body weight were not significantly different among the groups. The mean weekly capillary blood glucose values and exogenous insulin requirements were not changed by the SMS 201-995 therapy. Mean glycosylated hemoglobin A1 levels were unchanged in both the analogue- and placebo-treated groups at wk 12. Basal and postprandial glucose, free insulin, GH, and glucagon profiles were not influenced by the SMS 201-995 therapy throughout the study. Nocturnal glucose turnover rates (D-[3-3H]glucose technique) remained unaltered by the analogue therapy. Dose-dependent gastrointestinal (GI) adverse effects (e.g., diarrhea) were documented in the analogue-treated patients. Visual acuity and fundic photomicrographs of our patients were not changed by the analogue therapy. In conclusion, the prominent adverse GI effects our patients experienced preclude the use of larger doses of the analogue that may be necessary to suppress GH and glucagon and improve glucose control in type I diabetic patients.
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PMID:Metabolic effects of long-acting somatostatin analogue (sandostatin) in type I diabetic patients on conventional therapy. 265 40

A host of chemically diverse compounds have antidiarrheal potency, however, only a fraction of these agents has gained clinical acceptance. But regardless of their therapeutic status, the effects of these drugs have enhanced our understanding of the physiology and pathophysiology of the intestinal mucosa. Fluid- and electrolyte substitution are the primary therapeutic measures in severe diarrhea, for that purpose oral rehydration using glucose-sodium solutions has proven simple and effective. In addition gut-selective opiates, for instance loperamide, are indicated. Opiates not only decrease propulsive motor activity of the bowel but also increase intestinal water and electrolyte absorption, both effects are neuronally mediated. Antimicrobial drugs are necessary in only a small fraction of patients with diarrhea. Experimental findings have indicated possible future candidates for treatment of diarrhea: Besides opiates and glucose-electrolyte solutions water and electrolyte absorption is enhanced by alpha 2-adrenergic agents, corticosteroids, and somatostatin. Inhibitors of electrolyte secretion include phenothiazines and opiates, possibly because of binding to calcium-calmodulin, calcium-channel blockers, membrane-stabilizing agents for instance propranolol and inhibitors of prostaglandin-synthesis such as non-steroidal antirheumatic agents.
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PMID:[Antidiarrheal agents: tools and therapeutic agents]. 265 88


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