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)

Successful pharmacological arrest of haemorrhage might avoid the risk of aspiration associated with tamponade and early studies have suggested that the vasoactive agent somatostatin may be as effective and perhaps safer than tamponade in controlling variceal haemorrhage. In our view, vasopressin has not established a role in management but we retain an open mind regarding the potential use of terlipressin in combination with nitroglycerin. It is unlikely that any of these agents can improve significantly our ability to control variceal haemorrhage when compared to balloon tamponade but they may reduce the incidence of pulmonary complications and thereby reduce subsequent mortality. Tamponade has proved successful in controlling acute haemorrhage from oesophageal varices in our hands. Late complications continue to give cause for concern but until effective safe alternatives to tamponade are developed, we continue to advocate its use for emergency control of acute variceal haemorrhage. Our own studies have shown that the high mortality seen in this patient population may reflect the severity of the underlying liver disease rather than failure of a management policy employing oesophageal tamponade for the initial control of acute variceal haemorrhage.
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PMID:Balloon tamponade and vasoactive drugs in the control of acute variceal haemorrhage. 135 76

Although the mechanism initiating and maintaining variceal hemorrhage is not completely understood, there has been general agreement in recent years on the concept that variceal rupture occurs when the tension on the wall of the varices reaches a critical value (the rupture point) that leads to the leakage of the elastic components of the wall. If this hypothesis is true, the aim of pharmacological treatment should be to reduce variceal wall tension or to prevent any abrupt increase in this parameter. Some vasoconstrictor drugs are currently used in order to achieve these goals and in the attempt to stop the acute bleeding episode. All these agents decrease either portal pressure and azygos blood flow. Vasopressin although effective, has significant cardiac and gastrointestinal adverse effects that discourage its use. Combination with nitroglycerin reduces its adverse effects while maintaining or even enhancing the reduction in portal pressure. Glypressin, which acts as a slow-release preparation of vasopressin, has a longer duration of action and can be administered as single intravenous injections instead of continuous infusion. However, the similarity of effects of these drugs on systemic circulation leads to an overlapping spectrum of untoward effects. Somatostatin and the synthetic octapeptide octreotide display similar pharmacological effects on splanchnic hemodynamics but have a better tolerability profile. Thanks to its longer duration of action and ease of administration, octreotide could become the drug of choice for the early, pre-hospital management of bleeding varices. A different approach to the pharmacological treatment of variceal bleeding may be the use of compounds, like metoclopramide and domperidone, that increase the lower esophageal sphincter pressure (LESP), thereby reducing the inflow of blood flow into the submucous venous plexus of the esophagus and hence into the esophageal varices. However, more studies are needed before these compounds be considered a real alternative to the above established drugs.
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PMID:Clinical pharmacology of active variceal bleeding. 136 76

Vasoactive drug therapy is the only therapy that can be administered immediately to patients with suspected variceal bleeding. The optimal agent is not yet available, but somatostatin or octreotide, glypressin and vasopressin and nitroglycerin are the best candidates. Somatostatin and octreotide have the best therapeutic index as they have very few side effects. They compare well to the other agents in comparative randomized trials. In addition to being used prior to sclerotherapy, vasoactive agents may show benefit when used in combination with endoscopic methods and in the immediate interval thereafter in order to prevent early re-bleeding. This remains to be tested in clinical trials.
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PMID:Medical management of bleeding esophageal varices. 136 77

Variceal bleeding is the most important complication of portal hypertension. Mortality due to the first variceal bleeding is very high (50%) and of those surviving a variceal bleeding episode, up to 80% may rebleed. Proper management of the acute variceal bleeding episode, the prevention of rebleeding and primary prophylaxis for variceal haemorrhage are therefore mandatory in order to improve the morbidity and mortality of cirrhotic patients with variceal bleeding. Injection sclerotherapy would be the treatment of choice for acute variceal bleeding. Drug treatment in the form of either a combined vasopressin-nitroglycerin regimen or somatostatin may be used as an alternative. Patients not responding to these treatments should be referred for surgery. For the prevention of variceal rebleeding, non-selective beta-blockers should be tried first, reserving long-term injection sclerotherapy for patients with contraindications or intolerance to beta-blockers or in whom beta-blocker therapy has failed. Surgical rescue in the form of either shunt surgery or lever transplantation should be considered if either treatment fails. A new technique, transjugular intrahepatic portosystemic stent-shunt (TIPSS) may replace shunt surgery in the future. Beta-blockers is the treatment of choice for primary prophylaxis of variceal haemorrhage and has a role in preventing acute and chronic bleeding from congestive gastropathy. However, the above sequential approach from the least invasive to the more invasive therapeutic options may not be appropriate for all cirrhotic patients with variceal bleeding.
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PMID:Management of variceal haemorrhage. 136 89

Following the demonstration that somatostatin lowered portal pressure in cirrhotic patients with portal hypertension, 2 uncontrolled reports suggested that the hormone might be useful in the control of acute variceal haemorrhage. Subsequently, a number of randomised controlled trials have indicated that somatostatin may have an efficacy as good as or better than either vasopressin or combined vasopressin and nitroglycerin therapy and is associated with fewer side effects. Somatostatin has an efficacy comparable to balloon tamponade, histamine-2-receptor antagonists and injection sclerotherapy. One double-blind randomised controlled trial demonstrated a significant benefit of somatostatin over placebo in the control of variceal bleeding whereas a second did not show any significant difference between treatments. In all the controlled trials, the average control rate achieved with somatostatin administration was 69% and it was not associated with any major side effects. Somatostatin administration has also been shown in uncontrolled series to be very effective in controlling postinjection sclerotherapy bleeding from the varices per se, and from oesophageal ulcers and oesophagitis. Few data are available on the long acting analogue of somatostatin, octreotide, but preliminary data suggest that it may be as effective and safe as the native hormone in controlling the acute variceal bleeding and postinjection sclerotherapy haemorrhage. It is concluded that there may be a case for instituting somatostatin therapy as soon as the patient enters hospital to facilitate sclerotherapy, and for continuing treatment for 5 days after sclerotherapy when the risk of recurrent bleeding is highest.
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PMID:Somatostatin in acute bleeding oesophageal varices. Clinical evidence. 138 69

Variceal bleeding has a high mortality, as the majority of patients have cirrhosis, with hepatic coma, renal failure, ascites and clotting deficiencies as complicating factors. Bleeding varices must therefore be treated as an emergency. Resuscitation, endoscopic diagnosis and haemostasis are the cornerstones of treatment. Once bleeding varices have been identified, attempts to stop the bleeding must be made at once as this will lessen the chances of hepatic failure developing. Endoscopic sclerotherapy at the time of diagnosis is the best available treatment at present, although profusely bleeding varices can be difficult to see and inject. In these circumstances the passage of a Sengstaken tube should stop the bleeding, allowing later sclerotherapy to be successful. If rebleeding recurs and cannot be controlled, oesophageal transection with a stapling gun may be life-saving, although the varices may later recur and long-term endoscopic follow-up will be necessary. Portacaval shunting and the distal splenorenal shunt involve arduous surgery and are followed by a significant incidence of hepatic encephalopathy; they should be reserved for those few cases when simpler measures have failed, although shunts do lead to permanent decompression of the portal system. The acute variceal bleed may also be dealt with pharmacologically. Vasopressin, used in combination with nitroglycerin to lessen the harmful side-effects, is cheaper and as effective as terlipressin or somatostatin and its synthetic analogue octreotide. Several courses of injection sclerotherapy will be required to eliminate oesophageal varices. Thereafter, long-term follow-up will be necessary to deal with any recurrence. The place of non-selective beta-blockers is still contentious, but they do reduce portal pressure and may lessen the chance of rebleeding. There is also a growing role for hepatic transplantation, which not only eliminates the varices but also restores liver function to normal and greatly reduces the risk of subsequent hepatoma development.
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PMID:The management of variceal bleeding. 168 66

The main aim of conservative treatment of upper gastrointestinal bleeding in portal hypertension is aim to treat and prevent esophageal variceal hemorrhage. Controlled trials show that the hemostasis rate following vaso-active therapy (vasopressin and analogues, somatostatin) is only slightly superior to the spontaneous hemostasis rate. Complications caused by vasopressin treatment can be avoided by concomitant application of nitroglycerin or by alternative treatment with somatostatin. Balloon tamponade is slightly superior to vasopressin for arresting variceal hemorrhage. Injection sclerotherapy influences acute bleeding most positively. Analysis of controlled trials favors sclerotherapy for prophylaxis of rebleeding, but beta-adrenoceptor blockers appear to be almost equally good.
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PMID:Conservative treatment of upper gastrointestinal bleeding in portal hypertension. 168 47

Previous work described in the rat a circumscribed, partly somatostatinergic, interneuronal projection from the esophageal afferent part of the nucleus of the solitary tract (NTSc) to esophageal motor neurons in the compact formation of the nucleus ambiguous (NAcf: Cunningham and Sawchenko, J Neurosci 9:1668, 1989). In the present study, axonal transport, immunohistochemical and in situ hybridization histochemical techniques were used to determine whether enkephalin (ENK), a peptide known to be expressed in a number of somatostatin-containing medullary cell groups, is also expressed in the projection from the NTSc to the NAcf. The results may be summarized as follows: 1) cells immunoreactive (IR) for prepro-enkephalin (ppENK)-derived peptides were found in the NTSc in colchicine-pretreated animals; in untreated animals, a dense ENK-IR terminal field was observed in the NAcf: sections stained with antisera against dynorphin-related peptides showed sparse staining in both regions; 2) signal indicating the presence of ppENK messenger RNA (mRNA) was found over the NTSc, including over a majority of cells identified using a retrograde tracing technique as projecting to the region of the NAcf; the signal for ppENK mRNA signal was greater than that for prepro-somatostatin (ppSS) in the NTSc; 3) a combined anterograde tracing-immunohistochemical technique demonstrated a strong correspondence between the distribution of inputs from the NTS to the NAcf, and the distribution of endogenous ENK-IR varicosities; in addition, leucine (L)-ENK-IR was found in an appreciable number of varicosities in the NAcf that had been anterogradely labeled from the NTSc; 4) unilateral electrolytic lesions of the rostromedial NTS, which included the central subnucleus, virtually eliminated ENK-IR in the ipsilateral NAcf, while staining on the contralateral side was unaffected. Taken together, these studies provide evidence that ppENK- and ppSS-derived peptides are expressed in the pathway from the NTSc to the NAcf, a pathway thought to play a role in the reflex control of esophageal peristalsis.
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PMID:Enkephalin immunoreactivity and messenger RNA in a discrete projection from the nucleus of the solitary tract to the nucleus ambiguous in the rat. 185 14

There are three distinct phases during which treatment might influence the outcome in patients with portal hypertension and variceal bleeding: treatment of the active bleeding episode, the prevention of recurrent haemorrhage and perhaps most controversially the use of prophylactic therapy to avert the first bleeding episode. For the treatment of active haemorrhage injection sclerotherapy is almost certainly the treatment of choice when the expertise is available. In the absence of such, vasoconstrictor therapy continues to be widely adopted as a temporizing measure. The efficacy of vasopressin as a single agent has been limited by associated cardiovascular complications. The addition of nitroglycerin to a vasopressin regime has recently been shown to reduce such complications and to improve overall efficacy. Somatostatin represents an alternative vasoconstrictor with increasing evidence of efficacy in the absence of serious complications. Long-term injection sclerotherapy is widely accepted as the first line treatment to prevent recurrence of variceal haemorrhage although early rebleeding, prior to the obliteration of varices, represents an important limitation of therapy. Alternative local endoscopic therapy using tissue adhesives or banding of varices are under evaluation. The major claims of benefit initially attributed to oral propranolol for the prevention of rebleeding have now been considerably modified and a specific role remains to be defined. Both injection sclerotherapy and B-adreno-receptor have been proposed as prophylactic therapy to prevent the first variceal haemorrhage. Two extremely positive reports of prophylactic sclerotherapy have received little further support and there are now few protagonists of this approach.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A critical review of the medical treatment of portal hypertension. 198 46

Balloon tamponade and vasoactive drugs such as vasopressin, glypressin, vasopressin and nitroglycerin combined and somatostatin are the mainstay of noninvasive emergency treatment of bleeding gastroesophageal varices. However, their hemostatic efficacy is limited and recurrent bleeding occurs in at least one half of the patients. Survival is not improved. Unwarranted side effects and complications may be severe. Therefore, vasoactive drugs and balloon tamponade can only serve as temporizing measures until some means of definite control of bleeding such as sclerotherapy is available.
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PMID:[Immediate conservative therapeutic measures in acute variceal hemorrhage (including catheter blockage)]. 198 74


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