Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to evaluate the effects of octreotide, a long-acting somatostatin analogue, on canine gastric mucosal blood flow and hemodynamics. We hypothesized that octreotide might decrease gastric mucosal blood flow without causing adverse hemodynamic effects. Two groups of dogs were anesthetized (six normal dogs and six dogs with prehepatic portal hypertension), and each dog was administered intravenous octreotide, normal saline solution, and vasopressin for 30 minutes on separate days in a blinded, randomized fashion. Vasopressin was included as treatment for a positive control. Gastric mucosal blood flow was assessed at the fundus, corpus, and antrum by endoscopic reflectance spectrophotometry. A femoral arterial catheter monitored systemic blood pressure and heart rate. Treatment responses for all observations were calculated for each dog as a percentage of baseline values. For mucosal blood flow, treatment responses did not differ significantly over time or between animal group or gastric location. Octreotide significantly decreased indices of hemoglobin concentration (-19%, p = 0.01) and oxygen saturation (-17%, p = 0.0002) compared to saline (-9% and -7%, respectively). The mean arterial pressure was increased after octreotide compared to saline (+23% versus +7%, p = 0.01), but octrotide had no effect on heart rate (+2% versus +1%). Vasopressin also decreased the indices of hemoglobin concentration (-34%) and oxygen saturation (-82%) significantly more than saline (p = 0.001). Vasopressin increased mean arterial pressure (+55%), but also caused reflex bradycardia (-22%) significantly more than saline (p = 0.001). We conclude that octreotide decreases canine gastric mucosal blood flow and appears to cause minimal hemodynamic changes.
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PMID:Octreotide decreases canine gastric mucosal blood flow: a controlled assessment by endoscopic reflectance spectrophotometry. 816 36

1. It has been reported that ortreotide partially corrects the hyperdynamic state in patients and animals with portal hypertension. The aim of the present study was to investigate whether chronic administration of octreotide can increase vascular responsiveness in rats with portal hypertension. 2. Portal hypertension was induced by partial portal vein ligation. Octreotide was given for 9 days subcutaneously (100 micrograms/kg every 12 h) starting 1 day before ligation. The aorta and mesenteric artery were then removed to study contraction after pressure recording. 3. Octreotide treatment significantly reduced portal pressure and plasma glucagon concentrations compared with the vehicle-treated group. Both phenylephrine and vasopressin induced concentration-dependent contractile responses in the aorta and mesenteric artery from both groups. The maximum contractile responses to phenylephrine and vasopressin in aorta and mesenteric artery were significantly greater in the octreotide-treated group than in the vehicle-treated group. The EC50 values for phenylephrine and vasopressin were significantly different in the aorta, but not in the mesenteric artery, but not in the mesenteric artery, between the two groups. In contrast, octreotide treatment did not alter the contractile responsiveness of arteries rom sham-operated rats. 4. These results show that, in rats with portal vein stenosis, octreotide increases arterial contractile responsiveness and reduces portal pressure.
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PMID:Chronic administration of octreotide increases vascular responsiveness in rats with portal hypertension. 894 99

Acute bleeding due to esophageal varices continues to be a life-threatening complication of liver disease. Despite the availability of improved therapy, mortality continues to be high. Octreotide has been shown to be at least as effective as vasopressin in the treatment of bleeding varices, with fewer and less severe systemic adverse effects. In addition, octreotide has also been consistently associated with a decreased need for transfusions. Octreotide has been used safely in patients without serious cardiovascular disease when administered as a continuous intravenous infusion of 25 micrograms/h for 24 hours with or without an initial 100-micrograms bolus dose. Since these trials have used small numbers of patients, the ability to detect small but clinically important differences has been limited. Additional controlled trials comparing octreotide with the combination of vasopressin and nitroglycerin are needed to more clearly determine the efficacy and cost-effectiveness of therapy. Furthermore, the optimal dosage, duration, and route of administration of octreotide in the treatment of bleeding esophageal varices has yet to be determined.
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PMID:Octreotide or vasopressin for bleeding esophageal varices. 903 26

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 basic principles of managing variceal bleeding have changed little in the last fifty years. Fluid resuscitation, efforts to induce intra-variceal thrombosis, and treatments to reduce portal pressures remain the keys to successful therapy. However, the last decade has seen the introduction of new modalities which have improved treatment efficacy and safety. Octreotide and, at many institutions, terlipressin have supplanted intravenous vasopressin as acute pharmacologic therapy for variceal bleeding. Endoscopic management of variceal bleeding now includes endoscopic variceal ligation in addition to the widely practiced endoscopic sclerotherapy. Placement of transjugular intrahepatic portosystemic shunts has been proven to be a reliable means of emergently inducing a reduction in portal pressure and stopping variceal hemorrhage. In the out-patient setting, therapy with non-selective beta-blockers, often coupled with oral nitrates, is increasingly accepted as a means of improving portal hypertension and reducing a patient's risk of first hemorrhage or recurrent variceal bleed. This review focuses on the history and evolution of management strategies for variceal bleeding, discusses the physiologic basis for each type of therapy, summarizes current treatment approaches, and addresses recent developments in the field.
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PMID:The management of variceal bleeding: past, present and future. 998 99

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

Esophageal and gastric variceal bleeding is one of the most severe complications of portal hypertension and with high mortality. The aim of the therapy is to stop bleeding, replace the lost amount of blood and erythrocytes, treat coagulopathy, prevent rebleeding and improve liver function. Commonly accepted method to stop bleeding from varices is endoscopic hemostasis. Four vasoactive drugs, two natural peptides (vasopressin and somatostatin) and their analogues (terlipressin and octreotide) can control acute bleeding from gastric and esophageal varices. They lower portal pressure and the pressure in colateral circulation by vasoconstriction in splanchnic basin, and by inhibition the activity of endogenous vasodilatators. The high incidence of serious side-effects of vasopressin, even with nitroglycerin, has limited its application and decreased the use of this drug, with its abandonment in Europe. The vasopressin analogue, terlipressin, has a lower number of side-effects and is more effective in control of bleeding. Early terlipressin application at home, prior to hospital admission, diminishes mortality due to bleeding, thus attaching additional importance to this drug. Somatostatin, when applied as intravenous bolus injection, controls acute bleeding very efficiently and quickly. Five day somatostatin infusion after endoscopic hemostasis prevents rebleeding, with minimal side-effects. Octreotide is very efficient in long-term therapy of endocrine tumors due to its longer half-life, better hormone inhibition, and simple application compared to somatostatin. Like somatostatin, it can also control variceal bleeding. It appears that the long-term subcutaneous octreotide application prevents rebleeding and improves liver function, all of which yields a new dimension to its use.
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PMID:[Drug therapy of hemorrhage in esophageal and gastric varices: role of vasoactive drugs]. 1129 Dec 71

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

Somatostatin and its analogues have been compared with a variety of other treatments for the treatment of variceal bleeding in cirrhotic patients. Meta-analyses of studies comparing somatostatin or octreotide with vasopressin or terlipressin have shown that somatostatin is somewhat superior to vasopressin and equivalent to terlipressin in controlling bleeding and has significantly fewer side effects; no difference in mortality was observed. Octreotide was somewhat better than vasopressin and terlipressin in controlling bleeding, with similar mortality. Meta-analysis of trials comparing somatostatin or octreotide with endoscopic sclerotherapy shows that both drugs are equivalent to sclerotherapy for bleeding control, early rebleeding and survival. Complications are much less frequent with drug treatment. Nine trials have compared endoscopic therapy with therapeutic regimens combining endoscopic treatment with somatostatin, octreotide or vapreotide. Meta-analysis show that the combined regimens increase the 5 days bleeding control rate of endoscopic treatments by over 20%, although there is no difference in mortality. Comparisons of somatostatin and octreotide with combined regimens of sclerotherapy + somatostatin and sclerotherapy + octreotide have shown that the combined regimens were better than drug treatments alone in controlling bleeding and preventing early rebleeding, while complications were significantly less frequent with drug therapy.
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PMID:Somatostatin, somatostatin analogues and other vasoactive drugs in the treatment of bleeding oesophageal varices. 1507 17

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent monogenic hereditary disease as well as the most studied inherited kidney disease. Two drugs have recently been authorized that can slow down the progression of the disease: Tolvaptan (vasopressin receptor antagonist) and Octreotide-LAR (long-acting somatostatin analogue); they both are able to reduce the activity of cyclic adenosine monophosphate (cAMP) and therefore have anti-proliferative and anti-secretory effects. This review analyzes the main trials published to date demonstrating the effects on disease progression in patients with ADPKD and illustrates the indications for identifying subjects eligible for therapy.
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PMID:[ADPKD treatment: Tolvaptan and Octreotide]. 3183 Mar 92


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