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)

To study the long-term effects of pharmacological combination therapy, a comparison was made of the haemodynamic changes in patients with cirrhosis and portal hypertension following a 4-week treatment of propranolol or nipradilol, a new nonselective beta-blocker with nitrovasodilating effect. Nipradilol (12 mg/dag, n = 12) significantly diminished wedged hepatic venous pressure (WHVP, 25 +/- 16%), the hepatic venous pressure gradient (HVPG, 20 +/- 12%), and estimated hepatic blood flow (EHBF, 18 +/- 16%). Propranolol (30 mg/day, n = 11) also caused a significant reduction in WHVP (22 +/- 21%) and HVPG (24 +/- 21%), but not in EHBF. The percentage of portal pressure reduction and the frequency of nonresponders did not differ between the nipradilol and propranolol groups. Both agents reduced heart rate by approx. 20%. Nipradilol, however, did not cause a significant reduction in cardiac index (CI) versus a 14% reduction by propranolol. Pulmonary capillary wedge pressure and central venous pressure, an index of preload, were decreased slightly in the nipradilol group. When nonresponders were excluded, there was a significant correlation of the percentage of reduction between WHVP and CI or systemic vascular resistance, in the nipradilol group. These results indicate that nipradilol may have potent hypotensive effects on portal hypertension, similar but not superior to propranolol. Nipradilol, at the dosage used in the present study, did not appear to exert a nitrovasodilating effect to enhance the portal pressure reduction induced by beta-blocking action.
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PMID:Long-term haemodynamic effects of a 4-week regimen of nipradilol, a new beta-blocker with nitrovasodilating properties, in patients with portal hypertension due to cirrhosis. A comparative study with propranolol. 135 76

Thirty two patients with cirrhosis of the liver of Child's B and C class and an episode of endoscopically proven variceal bleed were randomly assigned to receive endoscopic sclerotherapy (EST) or oral propranolol for the prevention of recurrent upper gastrointestinal bleeding. EST was performed at 3 week intervals using 1% polidocanol intravariceally, till eradication of varices. Propranolol dose was adjusted to reduce the resting heart rate by 25% of the basal value (mean +/- SD, 194.3 +/- 63.9 mg/day) Two patients in the propranolol group were excluded within 48 hours due to side effects of the drug. Thirty patients (EST-16, propranolol-14) completed the trial. Patients were followed up for a maximum of 480 days. Mean follow-up in the EST and propranolol groups was 217 and 243 days respectively. The median bleeding free intervals were 480 and 194 days and number of rebleeding episodes was eight and 16 respectively in the EST and propranolol groups (both p = ns). Our study suggests a trend in favor of EST in preventing variceal rebleeding in patients with hepatic cirrhosis who belong to Child's B and C classes.
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PMID:Endoscopic sclerotherapy versus propranolol in prevention of recurrent variceal bleeding in patients with child's B and C cirrhosis: a preliminary report. 142 34

Cirrhosis of the liver is typically accompanied by low plasma levels of the three branched chain amino acids (BCAA). These patients also demonstrate increased concentrations of several hormones such as insulin, glucagon and catecholamines. Catecholamines have been shown to influence the plasma levels of amino acids in healthy subjects and diabetics. In the present study, amino acid concentrations were investigated before and up to 3 hours after beta blockade (Inderal, 40-80 mg, n = 10) or fasting (n = 8) in cirrhotic patients. In the basal state the patients had low levels of all three BCAA, as compared with healthy subjects. Norepinephrine was more than 3 times as high in the patients (3.65 +/- 0.6 vs. 0.84 +/- 0.08 nmol/l, p < 0.01) while epinephrine was only slightly raised (0.43 +/- 0.1 vs. 0.25 +/- 0.06 nmol/l, NS). Significant correlations were observed between the concentrations of norepinephrine and individual as well as the sum of the three BCAA (r = 0.43-0.62, p < 0.05-0.001), while no correlation was observed between the BCAAs and epinephrine or insulin. Three hours after beta blockade the concentrations of leucine (basal: 74 +/- 6, 180 min: 89 +/- 6 mumol/l, p < 0.05) and valine (basal: 110 +/- 10, 180 min: 132 +/- 11 mumol/l, p < 0.01) had increased significantly. A similar tendency was observed for isoleucine. No changes were observed after prolonged fasting. The results suggest that catecholamines, primarily norepinephrine, might contribute to the low levels of BCAA in cirrhotics.
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PMID:Influence of beta blockade on branched chain amino acid concentrations in cirrhosis. 145 31

Sixteen patients (15 males, aged 48-70) affected by liver cirrhosis and oesophageal varices were subjected to duplex-Doppler ultrasonographic study (DDUS). Four patients (three with a portal thrombosis and one with a hepatofugal portal flow) were excluded from the subsequent pharmacological test. The twelve remaining patients took part in a double blind cross-over study that evaluated the variations of heart rate (HR), mean systemic arterial pressure (SAP), portal vein diameter (PVD), maximal and mean portal flow velocity (PFV) after the administration of either 40 mg of propranolol or placebo per os, on two consecutive days. Propranolol caused no significant variation in mean SAP and in PVD, whereas it reduced the HR from 67.7 +/- 8.0 to 58.4 +/- 7.0 beats/min (mean +/- s.d.; P less than 0.001); the maxPFV dropped from 18.2 +/- 5.4 to 14.0 +/- 3.7 cm/s (P less than 0.001) and the meanPFV dropped from 15.3 +/- 4.1 to 13.2 +/- 3.1 cm/s (P less than 0.005). No significant variation was observed with placebo. After propranolol administration eight patients exhibited a significant maxPFV decrease, whereas the other four patients exhibited only a drop in HR, suggesting either drug inefficacy, inappropriate dosage or inadequate duration of treatment. DDUS is the only non-invasive method for the examination of the portal vein system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Duplex-Doppler ultrasonography in the evaluation of cirrhotic patients with portal hypertension and in the analysis of their response to drugs. 151 65

The two main causes of gastrointestinal bleeding in cirrhosis are oesophageal varices and portal hypertensive gastropathy (PHG). Rebleeding from varices can be prevented by beta-blockers, but it is not clear whether these drugs effectively reduce rebleeding from PHG. 54 cirrhotic patients with acute or chronic bleeding from severe PHG took part in a randomised, controlled trial to investigate the efficacy of propranolol in prevention of rebleeding from PHG. 26 patients were randomised to receive propranolol daily at a dose that reduced the resting heart rate by 25% or to 55 bpm (20-160 mg twice daily), throughout mean follow-up of 21 (SD 11) months. 28 untreated controls were followed-up, with the same examinations, for 18 (13) months. The actuarial percentages of patients free of rebleeding from PHG were significantly higher in the propranolol-treated patients than in the untreated controls at 12 months (65% vs 38%; p less than 0.05) and at 30 months of follow-up (52% vs 7%; p less than 0.05). Propranolol-treated patients had fewer episodes of acute bleeding than controls (0.010 [0.004] vs 0.120 [0.040] per patient per month). Multivariate analysis showed that absence of propranolol treatment was the only predictive variable for rebleeding. Actuarial survival was slightly higher in the propranolol group than in the controls, but the difference was not significant. Thus, long-term propranolol treatment significantly reduces the frequency of rebleeding from severe PHG, and may improve the prognosis of cirrhotic patients with this disorder.
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PMID:Propranolol in prevention of recurrent bleeding from severe portal hypertensive gastropathy in cirrhosis. 167 64

Several agents can reduce portal pressure in patients with portal hypertension. These drugs act in different ways and have different actions. Several hemodynamic investigations have elucidated the effects of beta-blockade on the splanchnic circulation. Propranolol and other non-selective beta-blockers significantly decreased portal pressure in patients with cirrhosis. In some patients, beta-blockers did not decrease portal pressure while cardiac output and azygos blood flow significantly decreased. The cause and severity of cirrhosis do not influence the effects of beta-blockers. The efficacy of beta-blockers in the prevention of the first gastrointestinal bleeding is well established. Meta-analysis showed that among patients receiving beta-blockers, 10 per cent bled 1 year after inclusion as against 30 per cent in the placebo group. A significant difference in survival rate was also observed between the two groups. The efficacy of beta-blockers in the prevention of recurrent gastrointestinal bleeding is variable; 5 trials showed a significant difference while 3 did not show any significant difference between patients receiving beta-blockers and those receiving a placebo. Meta analysis showed a significant difference in the risk of rebleeding but did not show any difference in survival rate. Thus, beta-blockers reduce the degree of portal hypertension in patients with cirrhosis and decrease the risk of gastrointestinal bleeding in compliant patients.
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PMID:[Medical treatment of portal hypertension]. 167 66

Four pharmacons were tested on an acute portal pressure lowering effect in an experimental animal model with 25 normal and 25 rats with Thioacetamide-toxic liver cirrhosis. Invasive measurements of arterial and portal pressure were made under Hexobarbital-Sodium anaesthesia during 30 minutes after pharmacon application. The portal pressure of cirrhotic rats was under basic conditions 9.5 +/- 1.5 mm Hg and significant higher as in normal animals (5.3 +/- 0.9 mm Hg, p less than 0.01). After 10 mg/kg body mass Propranolol the portal pressure decreased in both animal groups small but not significantly over the whole measurement time. 1 mg/kg Verapamil lowered arterial middle pressure significantly, but increased portal pressure at all 15-20% in both animal groups. Application of 0.1 mg/kg Prazosin decreased the arterial middle pressure at all 5-15% and the portal pressure at all 20-30% in both study groups (both significantly). For Canrenoat-Potassium (20 mg/kg) no clear effect could by evaluated on portal pressure. The model of Thioacetamide-toxic cirrhosis of the rat offers conditions like cirrhosis in human medicine in order to study the effects of portal pressure lowering pharmacons. Propranolol and Prazosin decrease portal pressure and should by further investigated.
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PMID:[Pharmacological lowering of portal pressure in normal rats and in experimental liver cirrhosis]. 181 60

To assess the effectiveness of propranolol in the prevention of initial variceal hemorrhage, a double-blind, randomized trial was carried out in three centers. Patients with cirrhosis (78% alcoholic), hepatic venous pressure gradients greater than 12 mm Hg and endoscopically proven esophageal varices were randomly assigned to propranolol (51 patients) or placebo (51 patients). Of the 102 patients, 58% were Child's class A, 34% were Child's class B and 8% were Child's class C. Daily dosage was determined by the administration of progressively increasing doses of propranolol with the hepatic vein catheter in place to achieve a 25% decrease in hepatic venous pressure gradient, a decrease in hepatic venous pressure gradient to less than 12 mm Hg or a decrease in resting heart rate to less than 55 beats/min. During a mean follow-up period of 16.3 mo, 11 patients in the placebo group (22%) bled from esophageal varices compared with 2 in the propranolol group (4%) during a mean period of 17.1 mo (p less than 0.01). Three additional patients (6%) in the placebo group bled from portal hypertensive gastropathy compared with none in the propranolol group. Propranolol appeared effective in preventing bleeding from large varices. Eleven deaths (22%) occurred in the placebo group compared with eight deaths (16%) in the propranolol group (NS). The mean dose of propranolol was 132 mg/day, and the median dose was 80 mg/day. Using a compliance index (pill count, clinic attendance, alcohol and propranolol levels and alcohol history), 81% of the propranolol patients and 77% of the placebo patients were considered compliant. Complications severe enough to require cessation of therapy occurred in eight patients (16%) in the propranolol group and four in the placebo group (8%) (NS). We conclude that propranolol effectively prevents the first variceal hemorrhage in patients with alcoholic cirrhosis and large esophageal varices but does not improve survival.
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PMID:Propranolol in the prevention of the first hemorrhage from esophagogastric varices: A multicenter, randomized clinical trial. The Boston-New Haven-Barcelona Portal Hypertension Study Group. 202 94

Propranolol and endoscopic sclerosis of esophageal varices are the two approaches currently used in prophylaxis of the first gastrointestinal hemorrhage in the cirrhotic patient. One hundred twenty-six cirrhotic patients with esophageal varices and no histories of bleeding were included in the trial regardless of the gravity of the cirrhosis or the size of the esophageal varices. Patients with hepatocarcinomas or other cancers, clearly impossible follow-up, previous treatment for portal hypertension or contraindication to beta-blockers were excluded. After randomization, 43 patients received propranolol twice daily at a dose reducing the heart rate by 25%; 42 patients were treated with intravariceal and extravariceal injections of Polidocanol; 41 control patients received vitamin K orally as placebo. The patients were seen at 3-mo intervals for 2 yr. On entry to the trial the three groups were comparable in terms of clinical and biological parameters, including size of esophageal varices (grade I = 51, grade II = 54, grade III = 17), Child-Pugh classification (A = 29, B = 61, C = 32) and the origin of cirrhosis (alcoholic in 79% of cases). Twenty-four patients bled (two bled in the propranolol group, nine bled in the endoscopic sclerosis of esophageal varices group and 13 bled in the placebo group). Actuarial estimates (Kaplan-Meier) of the time of onset of first bleeding showed that the differences were significant between propranolol and placebo (p less than 0.004) and between propranolol and sclerotherapy (p less than 0.03) but not between sclerotherapy and placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preventive therapy of first gastrointestinal bleeding in patients with cirrhosis: results of a controlled trial comparing propranolol, endoscopic sclerotherapy and placebo. 225 57

In this study, the author intended to examine the validity of the inhaled hydrogen gas clearance method (i-H2) for determination of the hepatic blood flow (HBF), and also to show some applicabilities of the method in experimental animals and patients with liver diseases. Simultaneous determinations of HBF by i-H2 and electromagnetic flowmetry in rabbits revealed an excellent correlation between the values obtained by the two methods. Moreover, HBF in rabbits measured by i-H2 varied in parallel with that by thermocouple flowmetry or laser Doppler velocimetry after administration of norepinephrine, propranolol or glucagon. In carbon tetrachloride-treated rats, HBF measured by i-H2 correlated better with the severity of damage in the sinusoidal structure than the severity of hepatic cell injury or the serum levels of transaminases. HBF as determined by i-H2 was significantly decreased in acute hepatitis (AH), chronic inactive hepatitis (CIH), chronic active hepatitis (CAH), liver cirrhosis (LC) and fatty liver. Reduced HBF in AH returned to normal during recovery of the disease. The ratio of HBF in tumor/normal tissue was greater than 1.0 for hepatocellular carcinoma in contrast to the ratio of less than 1.0 for metastatic liver carcinoma. Propranolol caused a decrease in HBF by 31%, and vasopressin by 39% in patients with CIH or LC. In contrast, glucagon induced its increase by 65%, 35% and 17%, respectively, in patients with CIH, AH and LC.
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PMID:[Measurement of hepatic blood flow by the hydrogen gas clearance method. Experimental and clinical observations]. 236 96


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