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)

The search for new pharmaceutical treatments has led to the isolation of products from a range of natural sources. Analogues synthesized from these products may possess an improved therapeutic effect over their natural counterparts. Two natural peptides, vasopressin and somatostatin, possess pronounced in vivo effects, so do their analogues terlipressin and octreotide. Vasopressin is a powerful vasopressor, reducing portal pressure, and has been used to treat gastrointestinal haemorrhages. However, a number of adverse cardiovascular effects resulting from an increase in peripheral vascular resistance have been associated with this drug. Terlipressin, however, is more effective, has an improved safety profile and is associated with fewer side effects than vasopressin. Somatostatin, a growth regulatory hormone, achieves haemostasis by decreasing splanchnic blood flow, and is effective in preventing early rebleeding. Somatostatin is effective in treating bleeding oesophageal varices (BOV) and is associated with fewer and more transient side effects than terlipressin. Octreotide, however, has greater stability and a longer half-life than somatostatin, but has a less favourable safety profile. Octreotide displays a number of therapeutic advantages over somatostatin, but not in the treatment of gastrointestinal indications. The development of terlipressin from vasopressin has demonstrated a number of clinical advantages, while the development of octreotide from somatostatin has not shown any significant advantage in the treatment of BOV.
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PMID:Development of analogues: successes and failures. 959 98

The medical treatment of portal hypertension has experienced marked progress in the past decade due to the production of effective portal hypertension therapy. This has been possible because of the better understanding of the pathophysiological mechanisms leading to portal hypertension. A major step forward was the introduction of beta-blockers for the prevention of bleeding and rebleeding from gastroesophageal varices. Effective therapy requires the reduction of the hepatic venous pressure gradient (HVPG) to 12 mm Hg or below, or at least by 20% of baseline values. Unfortunately, this is only achieved in 1/3-1/2 of patients. The combination therapy associated with isosorbide-5-mononitrate and propranolol or nadolol administration enhances the fall in portal pressure and increases the number of patients in whom HVPG decreases more than 20% and below 12 mm Hg. Randomized trials (RCTs) support the fact that combination therapy is more effective than propranolol or nadolol alone and better than sclerotherapy. In the treatment of acute variceal bleeding, pharmalogical therapy offers the unique advantage of permitting the provision of specific therapy immediately after arrival to hospital, or even during transferral to hospital by ambulance, since it does not require sophisticated personnel. Terlipressin has proved to be effective and to decrease mortality from bleeding. RCTs have shown that this drug is as effective and safer than emergency sclerotherapy. Therapy should be maintained for five days to prevent early rebleeding. Somatostatin is probably as effective as terlipressin.
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PMID:Medical treatment of portal hypertension. 970 38

Recent advances in the knowledge of the pathophysiology of portal hypertension has opened new indications for the pharmacologic treatment of acute variceal bleeding. Treatment with vasoactive agents is immediately available, easy to use and can be considered as definitive or adjunctive to endoscopic therapy. The data from randomised trials of vasoactive drug treatment for acute variceal bleeding are reviewed, using meta-analysis where applicable. The use of vasopressin has been decreased as a consequence of its questionable efficacy and its high incidence of side effects. Terlipressin is the only drug that has been shown to improve survival, albeit in small trials and there are insufficient data of its use over 5 days. Somatostatin has been shown to have similar efficacy with terlipressin with significantly less side effects. The demonstrated efficacy of octreotide in acute variceal bleeding is less than terlipressin and somatostatin and it cannot be considered as drug of first choice. Somatostatin combined with sclerotherapy represents the optimal therapy today as this combination has been shown to be more effective than sclerotherapy alone and it is safe given over 5 days.
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PMID:Role of vasoactive drugs in the treatment of bleeding oesophageal varices. 1056 86

The medical treatment of portal hypertension has experienced a marked progress in the past decade due to the introduction of effective portal hypotensive therapy. This has been possible because of the better understanding of the pathophysiological mechanisms leading to portal hypertension. A major step forward was the introduction of beta-blockers for the prevention of bleeding and rebleeding from gastroesophageal varices. Effective therapy requires the reduction of the hepatic venous pressure gradient (HVPG) to 12 mmHg or below, or at least by 20% of baseline values. Unfortunately, this is only achieved in 1/3 to 1/2 of patients. Combination therapy, associating isosorbide-5-mononitrate and propranolol or nadolol administration enhances the reduction in portal pressure and increases the number of patients in whom HVPG decreases by more than 20% of baseline values and below 12 mmHg. Randomized clinical trials (RCT's) do support the concept that combination therapy is more effective than propranolol or nadolol alone, significantly better than sclerotherapy, and probably than endoscopic banding ligation. Therapy may be complemented by the association of spironolactone. The main inconvenience of pharmacological therapy is that there is no non-invasive method available to detect non-responders to treatment. Failures of drug therapy should be managed endoscopically. Failures of endoscopic treatment require 'rescue' by means of TIPS or shunt surgery. Patients with advanced liver failure should be considered for orthotopic liver transplantation, and put into a waiting list if eligible. In the treatment of acute variceal bleeding pharmacological therapy offer the unique advantage of allowing to provide specific therapy immediately after arrival to hospital, or even during transferral to hospital by ambulance, since it does not require sophisticated equipment and highly qualified medical staff. Vasopressin has been abandoned because of its toxicity, although this can be reduced by the combined administration of transdermal nitroglycerin. Terlipressin has longer effects and is more effective and safer than vasopressin alone or in combination with nitroglycerin. It has proved to be effective and to decrease mortality from bleeding in double-blind studies. RCT's have shown that this drug is as effective and safer than emergency sclerotherapy. Therapy should be maintained for five days to prevent early rebleeding. Somatostatin is probably as effective as terlipressin. Octreotide is probably useful after endoscopic therapy but can not be recommended as first line treatment. Endoscopic injection sclerotherapy and endoscopic banding ligation are very effective, but require well trained medical staff. There is an increasing trend for initiating therapy with a pharmacological agent, followed by semi-emergency endoscopic therapy as soon as a well trained endoscopist is available (within 12-24 hours), while maintaining drug therapy for 5 days. Failures of medical therapy may be treated by a second session of endoscopic treatment, but if this fails TIPS of emergency surgery should be done. In high-risk situations, such as bleeding from gastric varices or in patients with advanced liver failure, the decision for TIPS or surgery should be done earlier, after failure of the initial treatment.
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PMID:The sixth Carlos E. Rubio Memorial Lecture. Prevention and treatment of variceal hemorrhage. 1076 Dec 6

Upper gastrointestinal hemorrhage calls for a team approach. Early endotracheal intubation of unconscious patients helps to prevent aspiration. Erythromycin i.v. 20 min. before emergency endoscopy improves the diagnostic yield. Patients without increased risk of rebleeding may be treated on an outpatient basis. Band ligation is the gold standard for acute variceal bleeding. Terlipressin, somatostatin and octreotide are equally effective but require additional measures for prevention of late recurrence. Somatostatin and analogues used as adjunct to ligation slightly reduce the risk of rebleeding but not of death. Three to seven days of prophylactic antibiotics decrease the risk of uncontrolled or recurrent bleeding. Therapeutic failures are rescued by transjugular intrahepatic portosystemic shunting (TIPS). Patients with nonvaricose bleeding should only be treated when active hemorrhage or a "visible vessel" is found. First line treatment is endoscopic injection of diluted adrenalin or isotonic saline. Thermal coagulation is an alternative. Tissue-destructing sclerosants should be avoided. Clipping and injection of fibrin glue are second and third line measures. Proton pump inhibitors improve endoscopic hemostasis, however, it is unclear whether high i.v. doses are required. H. pylori must be eradicated to prevent late recurrence. Rebleeding is treated endoscopically with angiographic intervention or surgery as rescue measures.
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PMID:[Acute upper gastrointestinal hemorrhage. Diagnosis and management]. 1296 82

Bleeding from gastroesophageal varices is a frequent and often deadly complication of cirrhosis. The key factor in the natural history of esophageal varices is increased portal pressure, which in cirrhosis is due to the combination of increased hepatic vascular resistance and increased portal collateral blood flow. The maintenance and aggravation of this situation leads to the progressive dilation of the varices and thinning of the variceal wall, until the tension exerted by the variceal wall exceeds the elastic limit of the vessel, leading to variceal hemorrhage. Mortality from a variceal bleeding episode has decreased in the last two decades from 40% to 20% due to the implementation of effective treatments and improvement in the general medical care. Initial treatment should include adequate fluid resuscitation and transfusion to maintain the hematocrit at 25% to 30%, and prophylactic antibiotics (norfloxacin or amoxicillin-clavulanic acid). It is currently recommended that a vasoactive drug be started at the time of admission. Drug therapy may be started during transferal to hospital by medical or paramedical personnel and maintained for up to five days to prevent early rebleeding. Terlipressin, a vasopressin derivative, is the preferred agent because of its safety profile and proven efficacy in improving survival. Somatostatin is as effective as terlipressin, but may require higher than the usually recommended dosage. Octreotide is effective in conjunction with endoscopic therapy, but is the second choice because it has not been shown to reduce mortality. Vasopressin may be used where terlipressin is not available, but should be given in combination with transdermal nitroglycerin. Endoscopic elastic band ligation is the recommended endoscopic treatment, but injection sclerotherapy is still employed in many centres for active variceal bleeding. Failures of medical therapy (drugs plus endoscopic therapy) should undergo a second course of endoscopic therapy before proceeding to transjugular intrahepatic portosystemic shunt or, in rare occasions, to portosystemic shunt surgery. Administration of recombinant activated factor VII may decrease the number of treatment failures among patients with advanced liver failure (Child-Pugh class B and C).
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PMID:Medical management of variceal bleeding in patients with cirrhosis. 1499 22

Vasoactive drugs are safe and easy to administer, and universal treatment is the first-line approach for all patients with suspected variceal bleeding. There are strong arguments that the combination of vasoactive drugs, started as soon as possible, and endotherapy later on is the best therapeutic option, particularly in cases of ongoing bleeding at the time of endoscopy. The main action of vasoactive drugs is to reduce variceal pressure. This can be achieved by diminishing the variceal blood flow and/or by increasing resistance to variceal blood flow inside the varices. Changes in variceal pressure parallel changes in portal pressure. Drugs for the treatment of variceal bleeding can therefore be assessed by measuring the changes in portal pressure, azygos blood flow and variceal pressure. Vasoactive drugs can be divided into two categories: terlipressin (Glypressin), and somatostatin and its analogues, especially octreotide. Terlipressin significantly reduces portal and variceal pressure and azygos flow, is superior to placebo in the control of variceal haemorrhage and improves mortality. It is beneficial when combined with sclerotherapy. It also has the advantage that it might preserve renal function, one of the most important factors affecting the outcome of cirrhosis. As such, terlipressin is the most potent of the various vasoactive drugs. Somatostatin significantly reduces portal and variceal pressure and azygos flow, is superior to placebo in controlling variceal haemorrhage, and improves the success of sclerotherapy. The effect of octreotide is well established for preventing the increase in portal pressure after a meal (similar to blood in the intestines) though the effect of ocreotide on variceal pressure is controversial.
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PMID:Review article: a critical comparison of drug therapies in currently used therapeutic strategies for variceal haemorrhage. 1533 94

Treatment of portal hypertension is evolving based on randomised controlled trials. In acute variceal bleeding, prophylactic antibiotics are mandatory, reducing mortality as well as preventing infections. Terlipressin or somatostatin combined with endoscopic ligation or sclerotherapy is the best strategy for control of bleeding but there is no added effect of vasoactive drugs on mortality. Non-selective beta-blockers are the first choice therapy for both secondary and primary prevention; if contraindications or intolerance to beta-blockers are present then band ligation should be used. Novel therapies target the increased intrahepatic resistance caused by microcirculatory intrahepatic deficiency of nitric oxide and contraction of activated intrahepatic stellate cells.
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PMID:Management of portal hypertension. 1553 46

Gastrointestinal bleeding is a frequent and severe complication of portal hypertension. The most frequent cause of the bleeding is variceal rupture. Despite improvements in prognosis after variceal bleeding over the past two decades, the 6-week mortality rate remains high, ranging from 15 to 30%. Patients die from uncontrolled bleeding, early rebleeding, infection, or renal failure within the first weeks of a bleeding episode. Poor hepatic function, severe portal hypertension with a hepatic venous pressure gradient (HVPG) >20 mmHg, and active bleeding at endoscopy are independently associated with poor prognosis. First-line treatment includes resuscitation, prophylactic antibiotic therapy, the combined use of vasoactive drugs (started as soon as possible), and an endoscopic procedure. Reconstitution of blood volume should be done cautiously to maintain the haematocrit between 25 and 30%. Terlipressin, somatostatin, or octreotide can be used, and drug therapy is maintained from 48 h to 5 days. Ligation is the endoscopic treatment of choice in bleeding oesophageal varices; in gastric varices, obturation with cyanoacrylate is preferable. Uncontrolled bleeding should be an indication for a salvage transjugular portosystemic shunt (TIPS). In patients with Child-Pugh score A, shunt surgery might be an alternative to TIPS. Trials are currently ongoing into the precise indications of early TIPS in selected patients with an HVPG >20 mmHg, and into the usefulness of administration of recombinant activated factor VII when there is an active bleeding at endoscopy.
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PMID:Management of acute bleeding from portal hypertension. 1722 94

Variceal bleeding is one of the most severe complications of portal hypertension related to liver cirrhosis. Primary prophylaxis is considered mandatory in patients with cirrhosis and high-risk oesophageal varices, and once varices have bled, every effort should be made to arrest the haemorrhage and prevent further bleeding episodes. In acute variceal bleeding, vasoactive drugs that lower portal pressure should be started even before endoscopy, and should be maintained for up to 5 days. The choice of vasoactive drug should be made according to local resources. Terlipressin, somatostatin and octreotide can be used; vasopressin plus transdermal nitroglycerin may be used if no other drug is available. In variceal bleeding, antibiotic therapy is also mandatory. In primary and secondary prophylaxis, beta-blockers are the mainstay of therapy. In secondary prophylaxis (but not in primary prophylaxis) these drugs can be combined with organic nitrates.
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PMID:Acute variceal bleeding: pharmacological treatment and primary/secondary prophylaxis. 1834 84


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