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

Bleeding from esophageal varices is a feared complication of liver cirrhosis with high mortality. Pharmacotherapy of the acute bleeding episode with vasopressin has been shown to be effective in controlled studies, but side effects of this therapy are high and therefore replacement of vasopressin with somatostatin is under investigation. Another potential lead is the combination of vasopressin with vasodilators such as nitroglycerin. While acute pharmacotherapy of the patient with esophageal varices is well accepted, chronic or prophylactic pharmacotherapy is still in the investigative stage. Prophylactic therapy with beta-blockers, e.g. propranolol, has been shown to be effective in compensated patients with alcoholic cirrhosis. In patients with more advanced stages of the disease, or with cirrhosis of other etiology, the effectiveness of propranolol has not been proven. The mechanism of propranolol is similar to that of vasopressin, i.e. it lowers portal pressure by reducing portal flow. To maintain function of the affected organ, an alternative approach--namely lowering of portal pressure through reduction of the pathologically elevated resistance--should be actively investigated.
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PMID:[Pharmacological therapy of portal hypertension]. 286 82

The effects of a somatostatin analogue, SMS 201-995, on hepatic haemodynamics in the pig and on intravariceal pressure in man were studied. An infusion of 250 micrograms/h SMS 201-995 significantly reduced portal pressure, portal venous flow and hepatic artery flow in the pig. These changes in hepatic haemodynamics were accompanied by a reduction in cardiac output, a reflex slowing of the heart and an increase in arterial blood pressure. Splanchnic vascular resistance was increased following SMS 201-995 administration but hepatic vascular resistance remained unchanged. Administration of 50 micrograms SMS 201-995 reduced the intravariceal pressure from 27.4 +/- 2.5 to 15.8 +/- 2.1 mmHg in 9 patients with cirrhosis and portal hypertension. Administration of 50 micrograms SMS 201-995 also reduced portal pressure from 29 to 22 mmHg in a patient undergoing an elective portacaval shunt. These results suggest that SMS 201-995 may be of value in the control of bleeding oesophageal varices. Furthermore, because of its prolonged duration of action SMS 201-995 may be useful in the long term management of portal hypertension in patients with cirrhosis.
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PMID:Effects of a somatostatin analogue SMS 201-995 on hepatic haemodynamics in the pig and on intravariceal pressure in man. 286 2

Drugs used to treat portal hypertension cause constriction of mesenteric arterioles, reducing inflow to the portal venous system, portal pressure, and flow through portasystemic collaterals (such as esophageal varices). Vasopressin and somatostatin are direct vasoconstrictors. Propranolol acts by blocking vasodilatory beta 1 receptors and reducing cardiac output. A major side effect of vasopressin therapy is impaired cardiac performance secondary to coronary vasoconstriction and increased work against high arterial pressure. Infusion of vasopressin together with a cardiac inotrope or a vasodilator, and administration of vasopressin as an inactive "hormonogen" which is slowly released in vivo, may lessen adverse effects. Somatostatin appears to act selectively in the mesenteric circulation. Controlled trials indicate that vasopressin may be useful for controlling hemorrhage from esophageal varices and that somatostatin works at least as well as vasopressin. Propranolol treatment has been used to prevent variceal bleeding; however, controlled trials of its effectiveness have produced conflicting results.
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PMID:Drug therapy for portal hypertension. 287 47

Sixteen patients with cirrhosis of the liver and a history of haemorrhaging oesophageal varices all given Warren-type splenorenal bypasses were subjected to intraoperative measurement of portal flow and pressure after the administration of Somatostatin and Glypressin. Glypressin was distinctly more effective in producing a significant and long term reduction in portal flow and pressure. Somatostatin made no significant difference to these parameters.
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PMID:[Changes in portal hemodynamics during pharmacologic stimulation: somatostatin vs glypressin]. 287 31

A multicenter double-blind clinical trial was undertaken to evaluate the efficacy of a short-term somatostatin treatment versus a short-term vasopressin treatment on acute hemorrhage from esophageal varices in patients with liver cirrhosis and portal hypertension. Forty-nine patients with massive hemorrhage and endoscopic diagnosis of bleeding esophageal varices completed the study. Patients were randomly assigned to somatostatin treatment (24 patients: 250 micrograms/hr i.v. for 48 hrs) or vasopressin treatment (25 patients: 0.1 U/min i.v. for 48 hrs). The Sengstaken-Blakemore tube was utilized, when needed, for a six hour period. In case of failure the patients were crossed-over to the other treatment. Patients in whom the bleeding stopped at 48 hrs, were randomly assigned to somatostatin (250 micrograms/hr i.v.) or placebo for seven days. Bleeding stopped in 68% of patients treated with somatostatin and in 28% of patients treated with vasopressin (p less than 0.0013). Mortality rate was lower, but not significantly so, in the somatostatin group compared to the vasopressin group. No differences were noted between somatostatin and placebo in preventing bleeding recurrences. These data suggest that somatostatin, when combined if necessary with a 6 hour period of balloon tamponade, is more effective than vasopressin at low doses in controlling severe hemorrhage from esophageal varices in patients with liver cirrhosis and portal hypertension. A clinical use of somatostatin seems to be indicated in these patients.
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PMID:Effect of somatostatin in controlling bleeding from esophageal varices. 288 97

The oesophageal pH was recorded for 3 h after a test-meal in 27 healthy control subjects (group I), 40 patients with alcoholic cirrhosis (group II), and 22 patients with a normal liver and symptoms of gastro-oesophageal reflux (control refluxers). Gastro-oesophageal reflux was observed in 10 of the cirrhotic patients. Marked reflux episodes lasted longer in cirrhotic refluxers than in control refluxers (P less than 0.05). The frequency of ascites, bleeding from ruptured oesophageal varices, peripheral neuropathy and hepatic encephalopathy were not significantly different according to presence or absence of reflux. Plasma concentrations of gastrin, somatostatin, motilin and vasoactive intestinal peptide (VIP) were measured in groups I and II. Fasting plasma motilin levels, and the release of motilin and of VIP after the meal were higher in group II than in group I. Basal levels and post-prandial profiles of the four peptides tested did not differ between cirrhotics with or without gastro-oesophageal reflux. We conclude that in patients with alcoholic cirrhosis: gastro-oesophageal reflux is frequent (25%) and characterized by prolonged reflux episodes; reflux is not correlated with the degree of liver failure and plays no significant role in the rupture of oesophageal varices; and raised plasma motilin and VIP levels cannot account for the high incidence of reflux in cirrhotics.
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PMID:Gastro-oesophageal reflux and alcoholic cirrhosis. A reappraisal. 288 50

Secretin inhibits gastric secretion of acid and gastrin in dog and a physiological role of secretin as an enterogastrone has been suggested in this species. In man there are diverging results concerning the effect of secretin on gastric secretion. Secretin has been used in patients with upper gastrointestinal bleeding and positive results have been reported, but the patients included in these studies cannot be considered as massive bleeders. Until now no double-blind study comparing secretin with placebo has been reported. Somatostatin decreases splanchnic blood flow and gastric secretion in man. Somatostatin seems to be effective in achieving initial haemostasis in patients with bleeding oesophageal varices. The peptide has also been shown to stop severe and persistent peptic ulcer haemorrhage and to stop bleeding in patients treated with steroidal and non-steroidal anti-inflammatory drugs. In one double-blind trial in patients with upper gastrointestinal bleeding, somatostatin had no effect on either the number of emergency operations or the number of rebleedings. In another double blind study, when somatostatin was compared with placebo in patients with massive upper gastrointestinal bleeding, the peptide reduced the number of emergency operations. In conclusion, most studies show positive effects of somatostatin on variceal and peptic ulcer haemorrhage.
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PMID:Secretin and somatostatin in the treatment of upper gastrointestinal haemorrhage. 289 64

Transmural oesophageal variceal pressure was determined by direct puncture of the varices in 27 patients with liver cirrhosis and oesophageal varices. Variceal pressure was not influenced three to six minutes after somatostatin bolus administration and slightly increased during somatostatin infusion. Thus, potential haemostatic benefits of somatostatin cannot be explained by pressure reductions in the varices.
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PMID:Somatostatin does not reduce oesophageal variceal pressure in liver cirrhotics. 289 36

Portal hypertension is a common complication of chronic liver disease. Conventional therapy consists of surgery and palliative measures for the hemodynamic problem. It has been recently reported that somatostatin may reduce portal pressure without altering the systemic circulation and so reducing hepatic blood flow. This peptide also causes a significant fall in azygos circulation in patients with esophageal varices. The mechanism of this effect is unclear although suppression of intestinal vasodilating hormones and of glucagon have been claimed to play a role. Comparative clinical studies have shown somatostatin to be superior to the standard vasopressin treatment. Recent findings suggest that the efficacy of somatostatin can be increased by administering this peptide in repeated intravenous bolus injections. New derivatives, specially long-acting peptides, may eventually prove beneficial in the chronic treatment of this complication.
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PMID:Effects of somatostatin in patients with portal hypertension. 290 Feb 7

Current interest in the pharmacological manipulation of portal pressure centres on the long-acting somatostatin analogue SMS 201-995. Nine haemodynamically stable cirrhotic patients who had previously bled from oesophageal varices had wedged and free hepatic venous pressures and cardiac index measured, using a Swan-Ganz catheter, before and at 60, 120 and 180 min after beginning a 60-min infusion of 25 microgram/h of SMS 201-995. Seven clinically similar patients had the same measurements performed without SMS 201-995. In all patients cardiac index was found to decrease and systemic vascular resistance increase at 60 min, although heart rates and arterial blood pressures were unchanged. The group given SMS 201-995 was significantly different from the control group in sustaining a fall in wedged hepatic venous pressure and trans-hepatic venous gradient at 60 min. SMS 201-995 causes a fall in portal pressure without a significant systemic haemodynamic effect.
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PMID:The effect of a long-acting somatostatin analogue on portal and systemic haemodynamics in cirrhosis. 297 67


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