Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Terlipressin (Glypressin), a synthetic analog of vasopressin, induces arteriolar vasoconstriction which causes both a portal hypotensive effect and certain side-effects on the systemic circulation (elevated arterial pressure and reduced cardiac output). The combination of nitroglycerin with terlipressin might accentuate the portal hypotensive effect and prevent the side-effects on the systemic circulation. The aim of this study was to examine the systemic and splanchnic hemodynamic responses to terlipressin administered alone or combined with nitroglycerin in patients with cirrhosis. Systemic and splanchnic hemodynamics were measured before and 1 h after a bolus of terlipressin (1 to 2 mg IV) given alone (n = 10) or in association with nitroglycerin infusion (25 micrograms/min, n = 9). Terlipressin alone significantly increased the arterial pressure by 21%, systemic vascular resistance by 60%, and significantly decreased cardiac output by 23%. The right atrial and pulmonary pressures significantly increased and the wedged hepatic venous pressure and hepatic venous pressure gradient significantly decreased by 8% and 16%, respectively. The combined therapy decreased the cardiac output by 20%, but did not significantly modify the other systemic and splanchnic hemodynamic values. No significant differences were found between terlipressin and the combined therapy concerning changes in wedged hepatic venous pressure or hepatic venous pressure gradient. We conclude that in patients with cirrhosis, nitroglycerin prevents the deleterious vasoconstrictor and vasopressor effects of terlipressin. However, the combined therapy, as terlipressin alone, decreases the cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hemodynamic effects of the administration of terlipressin alone or combined with nitroglycerin in patients with cirrhosis]. 142 24

The haemostatic effect of terlipressin (triglycyl-lysine vasopressin; Glypressin) on bleeding from oesophageal varices was evaluated in a placebo-controlled, double-blind, randomized clinical trial. Patients with clinically suspected liver cirrhosis were included in the study if they had been admitted to hospital with an extensive haemorrhage within the last 24h before diagnostic endoscopy. The patients randomized after stratification for severity of liver disease. Terlipressin or placebo was administered as intravenous bolus injections every 4th h during a period of 24 to 36 h or until the clinical course necessitated active intervention (failure or withdrawal). Sixty patients entered the study; 31 patients were allocated to receive terlipressin, and 29 patients to receive placebo. Bleeding from varices was arrested in 28 of the 31 receiving terlipressin, as compared with 17 of the 29 receiving placebo (p less than 0.01). Patients receiving active drug required significantly fewer blood transfusions (p less than 0.05). Most of the side effects were classified as mild and were registered in the terlipressin group.
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PMID:Terlipressin (triglycyl-lysine vasopressin) controls acute bleeding oesophageal varices. A double-blind, randomized, placebo-controlled trial. 219 77

Terlipressin (Glypressin), a vasopressin analog, may be administered to patients with cirrhosis receiving a beta-adrenergic antagonist. Since terlipressin alone and beta-blockers alone both decrease portal pressure, a combination of these substances may have additional portal hypotensive effects. However, the negative side effects of terlipressin may be accentuated by long-term beta-blockade. Thus, the present study examined hemodynamic and metabolic responses to terlipressin in 12 patients receiving nonselective beta-blockers (propranolol or nadolol). Hemodynamics and oxygen (O2) -derived variables were measured prior to and 30 min after the administration (intravenous bolus) of terlipressin (1 to 2 mg, according to body weight). The hepatic venous pressure gradient and azygos blood flow significantly decreased (from 15.3 +/- 1.1 to 12.5 +/- 1.1 mm Hg, and from 0.6 +/- 0.1 to 0.5 +/- 0.1 liters/min, respectively). Arterial and pulmonary wedged pressures significantly increased. Heart rate, cardiac index, and O2 consumption were not significantly affected by terlipressin. In conclusion, in patients with cirrhosis being treated with a nonselective beta-blocker, terlipressin administration decreased portal pressure. Moreover, terlipressin induced only mild systemic hemodynamic effects in these patients. These results suggest that terlipressin can be administered in patients receiving a beta-adrenergic blocker.
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PMID:Hemodynamic and metabolic effects of terlipressin in patients with cirrhosis receiving a nonselective beta-blocker. 879 85

Hepatorenal syndrome is a frequent complication associated with extremely short survival in cirrhotic patients with alcoholic hepatitis. Vasopressin analogs have been reported to induce transient regression of hepatorenal syndrome in patients with cirrhosis. However, treatment withdrawal was followed by early recurrences in every case. We report the case of a 68-yr-old woman with severe alcoholic hepatitis complicated by hepatorenal syndrome. Terlipressin induced a prolonged recovery of renal function that was associated with improvement in hepatic function.
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PMID:Terlipressin may influence the outcome of hepatorenal syndrome complicating alcoholic hepatitis. 936 5

Hepatorenal syndrome is a rapidly lethal complication of cirrhosis. The present case provides further evidence of the efficacy of terlipressin in this context even with concomitant treatment with propranolol. A 56 year old male with HBV related cirrhosis developed renal failure characteristic of hepatorenal syndrome. He was also taking propranolol for primary prophylaxis of variceal bleeding. Terlipressin 6 mg/day was administered during haemodialysis and after 1 week plasma creatinine dropped from 6.2 to 2.8 mg%. Daily urinary volume, plasma sodium and natriuresis dramatically increased during the treatment. Discontinuation of the treatment led to a rapid relapse of renal failure (plasma creatinine from 1.8 to 2.2 mg%) and the drug was readministered until a successful liver transplantation could be performed 1 month after the beginning of the treatment. The patient has now a near normal renal function 3 months after transplantation.
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PMID:Treatment with terlipressin as a bridge to liver transplantation in a patient with hepatorenal syndrome. 965 23

Reducing morbidity and mortality from esophageal varices remains a challenge for physicians managing patients with chronic liver disease. For patients who have never bled from varices, prophylactic therapy with nonselective beta-blockers reduces the risk of initial variceal bleeding and bleeding-related death. Thus, patients with newly diagnosed cirrhosis should be considered for endoscopic variceal screening. All patients with Child's class B and C cirrhosis should be offered endoscopic screening, whereas those with Child's class A with evidence of portal hypertension (eg, platelet count less than 140,000 per milliliter, portal vein diameter larger than 13 mm, evidence of splenic varices on ultrasound) should be screened. The principal risk factors for variceal bleeding are variceal size, the presence of color changes on the variceal wall (indicative of decreased wall thickness), and degree of liver dysfunction. Patients with moderate or large sized varices and those with varices exhibiting color changes (eg, red wale marks, cherry red spots) should be treated with beta-blockers. Individuals without varices and those with small varices should undergo repeat endoscopy at approximately 2-year intervals. Patients unwilling or unable to take beta-blockers do not need to be screened. For patients with acute variceal bleeding, the combination of pharmacologic therapy plus endoscopic therapy is superior to either therapy alone. Octreotide is the drug most often used as initial therapy in the United States. Terlipressin is the preferred agent; however, it is not available in the United States. Endoscopy is performed as early as possible, and endoscopic injection sclerotherapy or endoscopic variceal band ligation is employed if variceal bleeding is confirmed or suspected. Endoscopic therapy should be repeated until the varices are obliterated completely. The addition of beta-blockers to endoscopic sclerotherapy or ligation may decrease the rate of rebleeding compared with receiving endoscopic treatment alone. Patients with bleeding refractory to combined medical plus endoscopic therapy should be considered for transjugular intrahepatic portosystemic shunts or shunt surgery.
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PMID:Variceal Hemorrhage. 1179 40

In cirrhosis, lipopolysaccharide (LPS, a product of Gram-negative bacteria) in the blood may cause septic shock. LPS-elicited induction of arterial inducible nitric oxide synthase (iNOS) results in nitric oxide (NO)-induced vasodilation, which causes arterial hypotension and hyporeactivity to alpha(1)-adrenergic constrictors. In vitro studies have suggested that vasopressin inhibits iNOS expression in cultured vascular smooth muscle cells exposed to LPS. Thus, the aim of this study was to investigate the effects of terlipressin administration (a vasopressin analog) on in vivo LPS-induced aortic iNOS in rats with cirrhosis. LPS (1 mg/kg, intravenously) was administered followed by the intravenous administration of terlipressin (0.05 mg/kg, intravenously) or placebo 1 hour later. Arterial pressure was measured, and contractions to phenylephrine (an alpha(1)-adrenoceptor agonist), iNOS activity, and iNOS expressions (mRNA and protein) were investigated in isolated aortas. LPS-induced arterial hypotension and aortic hyporeactivity to phenylephrine were abolished in rats that received terlipressin. LPS-induced aortic iNOS activity and expression were suppressed in terlipressin-treated rats. In conclusion, in LPS-challenged rats with cirrhosis, terlipressin administration inhibits in vivo LPS-induced aortic iNOS expression. Terlipressin administration may be a novel approach for the treatment of arterial hypotension and hyporeactivity to alpha(1)-adrenergic constrictors in patients with cirrhosis and septic shock.
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PMID:Terlipressin inhibits in vivo aortic iNOS expression induced by lipopolysaccharide in rats with biliary cirrhosis. 1239 16

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

Systemic vasodilatation and arterial hypotension, refractory to adrenergic vasopressors, portend a poor prognosis in patients with decompensated cirrhosis. The production of large amounts of nitric oxide, consequent to endotoxin-induced tumour necrosis factor (TNF)-alpha-mediated upregulation of inducible nitric oxide synthase (iNOS), has been suggested to be central to this phenomenon. Terlipressin has recently been shown in an animal model of cirrhosis to suppress endotoxin-induced TNF-alpha-mediated upregulation of iNOS, thereby preventing overproduction of nitric oxide and restoring normal vascular tone. We present the first evidence that this effect of terlipressin may also occur clinically, in a patient with Child-Pugh class C cirrhosis, endotoxaemia, a raised circulating TNF-alpha concentration, and marked systemic vasodilatation with refractory arterial hypotension. Beneficial effects of terlipressin on circulating nitrate and nitrite concentrations, haemodynamic status, plasma renin levels and indocyanine green clearance were comparable to those of the molecular adsorbent recirculating system (MARS). Our findings suggest that terlipressin may be the vasopressor agent of choice in patients with decompensated cirrhosis and provide a rationale for combination terlipressin and MARS therapy when the therapeutic response to either treatment alone is suboptimal.
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PMID:Nitric-oxide-lowering effect of terlipressin in decompensated cirrhosis: comparison to the molecular adsorbent recirculating system and correlation with clinical status. 1561 42


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