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)

The pharmacokinetics of famotidine were studied after the administration of a single intravenous dose of 20-mg to seven normal volunteers, six patients with chronic hepatitis, 14 patients with compensated cirrhosis, and seven patients with decompensated cirrhosis. The plasma terminal elimination half-life of famotidine was significantly prolonged and famotidine total body clearance was significantly reduced in patients with decompensated cirrhosis, whose creatinine clearance was 57.2 +/- 6.7 ml/min/1.48 m2, but these changes were not significant in patients with chronic hepatitis (creatinine clearance: 109.2 +/- 10.5 ml/min/1.48 m2) or in patients with compensated cirrhosis (creatinine clearance: 72.2 +/- 26.5 ml/min/1.48 m2 in comparison with normal volunteers. The total volume of distribution at steady state was not significantly different between the normal volunteers and the three groups of patients. Famotidine total body clearance showed a weak but significant correlation with the creatinine clearance (r = 0.66, p less than 0.001), serum albumin level (r = 0.51, p less than 0.01), and serum total bilirubin level (r = 0.36, p less than 0.05), which suggested that the reduction in clearance was due in part to the concomitant renal impairment, as well as hepatic dysfunction in these patients. In conclusion, famotidine total body clearance was reduced in decompensated cirrhosis, indicating that the dose schedule requires modification in patients with this condition.
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PMID:Pharmacokinetics of famotidine after intravenous administration in liver disease. 151 94

The renal tubular damage in liver cirrhosis was evaluated by measurement of urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in 32 patients with various stages of liver cirrhosis. The patients were divided to three groups (A, B, and C) according to Child's criterion and urinary NAG activity and renal function parameters were compared in these groups. As a result, urinary NAG activity in group C was significantly higher than group A and group B and slight elevation of serum BUN level and low creatinine clearance value were also observed in group C. In 8 patients who developed the renal failure in their clinical course the level of urinary NAG activity was markedly elevated in the early phase of renal failure. These results suggested that the measurement of urinary NAG activity was useful for early diagnosis of renal impairment in the cirrhotic patients.
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PMID:[Urinary N-acetyl-beta-D-glucosaminidase activity in liver cirrhosis with renal impairment]. 202 51

Central nervous system (CNS)-induced natriuresis was investigated in nonascitic rats with CCl4-induced cirrhosis (CTC rats) under pentobarbital anesthesia. At baseline, urine sodium output (UNa+V, in mumol.min-1.100 g body wt-1) (-30%, P less than 0.01) and mean arterial pressure (MAP, in mmHg) (-12%, P less than 0.001) were significantly reduced in CTC rats (n = 32) compared with matched controls (n = 34). In response to intracerebroventricular infusion of sodium-rich (349 mM) artificial cerebrospinal fluid (Na(+)-CSF infusion), UNa+V was significantly higher in CTC rats (2.8 +/- 0.3; n = 15) than in controls (1.7 +/- 0.2; n = 17; P less than 0.01); no differences were found in pressor changes (24 +/- 3 vs. 19 +/- 2). A similar but normal sodium CSF (150 mM) infusion did not influence UNa+V or MAP in any group (n = 12, both). In contrast, CTC rats (n = 5) showed, compared with controls (n = 5), significantly reduced natriuretic (UNa+V, 6.9 +/- 0.5 vs. 12.4 +/- 0.9; P less than 0.001) and pressor (+16 +/- 3 vs. +31 +/- 2; P less than 0.01) responses to an intravenous hypertonic sodium overload. Natriuresis induced by Na(+)-CSF infusion was related to increases in creatinine clearance (similar in both groups) and in fractional sodium excretion, which was significantly higher in CTC rats (5.90 +/- 0.15%) than in controls (3.65 +/- 0.14%; P less than 0.01). In summary, CNS-dependent efferent natriuretic mechanisms were preserved in CTC rats and were able to reverse renal tubular sodium retention in these animals. It is proposed that Na(+)-CSF infusion may be a useful tool for the study of renal sodium retention in experimental liver cirrhosis.
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PMID:Enhanced responsiveness to CNS-induced natriuresis in anesthetized nonascitic cirrhotic rats. 205 81

Quinapril is a new non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor. The drug undergoes hepatic hydrolysis into its major active diacid metabolite, quinaprilat, and two minor inactive metabolites. On a weight basis quinaprilat is three times as potent an ACE inhibitor as quinapril. Approximately 60 percent of an oral dose of quinapril is absorbed. In contrast with captopril, the absorption of quinapril is unaffected by food. Peak serum concentrations of quinapril and quinaprilat are achieved within one and two hours, respectively. Approximately 61 percent of an orally administered dose is excreted in the urine, principally as quinaprilat. The elimination half-life of quinaprilat is three hours, but is prolonged up to 11 hours in patients with renal dysfunction. Quinapril dose reduction is recommended in patients with a creatinine clearance of 0.50 mL/sec or less. In the elderly the elimination of quinaprilat is reduced and correlates well with renal function. In patients with cirrhosis the hydrolysis of quinapril to quinaprilat is impaired resulting in lower plasma quinaprilat concentrations and up to a two-fold increase in quinapril half-life. Quinaprilat has a strong binding capacity to tissue ACE allowing for once-daily dosing. The recommended starting dose for quinapril is 20 mg/d. The nature and incidence of adverse reactions to quinapril are similar to those of enalapril and captopril. Quinapril's antihypertensive efficacy is equal to that of captopril and enalapril. A small number of patients with congestive heart failure (CHF) have been treated with quinapril. Preliminary data indicate that quinapril is an equally effective therapeutic alternative to presently available ACE inhibitors in the treatment of CHF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quinapril: a new second-generation ACE inhibitor. 206 35

This case describes a patient with cholesteryl ester storage disease who underwent liver transplantation for progressive cirrhosis, portal hypertension, ascites, and uncontrollable gastrointestinal bleeding. Four and one-half years posttransplant, her growth improved, cholesterol levels have returned to normal, and she is clinically well except for mild hypersplenism and an elevated blood urea nitrogen (BUN) and creatinine. Serum triglycerides remain elevated, but there have been no signs of progressive renal, intestinal, vascular, or pulmonary disease.
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PMID:Liver transplantation for cholesteryl ester storage disease. 207 31

One year prospective study of 25 cirrhotic patients with portal systemic encephalopathy (PSE) admitted to the Emergency Care Centre in Belgrade was performed in order to investigate the significance of clinical, biochemical and electroencephalographic (EEG) parameters and blood ammonia in the diagnosis, differential diagnosis and prognosis of PSE. 15 cirrhotic patients without PSE (of comparable age, sex, duration and etiology of liver cirrhosis) constituted the control group. Ammonia levels were elevated in 84% of patients with PSE (112 +/- 72 mumol/l) and reached normal range within 3 +/- 0.44 days, but with no correlation to clinical improvement (p greater than 0.1). Ammonia levels correlated with the severity of PSE (p less than 0.05), but not with other biochemical parameters (prothrombin time, bilirubin, albumin, urea, creatinine, potassium). Overall mortality was 44% and was strongly correlated (p less than 0.01) to the severity of PSE. In addition, the mortality in patients with gastrointestinal bleeding and PSE was higher (p less than 0.05), than in PSE precipitated by other conditions. We concluded that the ammonia may be a primary diagnostic parameter for PSE in the absence of the most important diagnostical methods (EEG, psychometric tests). Secondly, ammonia are of great diagnostic importance in patients with coma of unknown origin and can help in deciding admission priorities. The ammonia levels do not appear to be a useful prognostic factor.
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PMID:[Ammoniemia in portosystemic encephalopathy--diagnostic, differential diagnostic and prognostic significance]. 207 39

Energy expenditure and substrate oxidation rate for fat, glucose and protein were evaluated by indirect calorimetry in 20 normal individuals, 35 patients with acute hepatitis and 22 patients with biopsy-proven alcoholic cirrhosis in the postabsorptive state. Measurements were done in the resting state after an overnight fast (10 to 12 hr). Oxygen consumption (ml/min/1.73 m2) in normal subjects, in patients with acute hepatitis and in patients with cirrhosis was 206.5 +/- 4.0 (mean +/- S.E.M.), 216.4 +/- 4.7 and 228.8 +/- 7.1 (p less than 0.05 vs. controls), respectively. When related to body surface area (kcal/min/1.73 m2), resting energy expenditure did not differ between normal subjects (0.98 +/- 0.02), patients with acute hepatitis (1.03 +/- 0.02) and cirrhotic patients (1.06 +/- 0.03). However, when related to 24-hr urinary creatinine excretion as an estimate of lean body mass, energy expenditure was increased in cirrhosis (p less than 0.0001). In cirrhosis an inverse association between the severity of liver disease according to Pugh and oxygen consumption and resting energy expenditure was found. In cirrhotic patients the percentages of total calories derived from fat (86% +/- 5%), carbohydrate (2% +/- 4%) and protein (12% +/- 1%) were different from those of normal controls who metabolized 45% +/- 4%, 38% +/- 4%, 17% +/- 1%, respectively. In acute hepatitis no alterations in metabolism could be found apart from a decreased protein oxidation rate. In conclusion no appreciable changes in energy metabolism exist in acute hepatitis. The pattern of fuel use in cirrhosis resembles that in starvation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Energy metabolism in patients with acute and chronic liver disease. 210 37

The effects of anaritide, a 25-amino-acid synthetic analogue of ANP, were evaluated in 28 patients with cirrhosis complicated by ascites and/or edema. Each patient received two doses of the agent, as well as an infusion of placebo. Six different doses were tested ranging from 0.015-0.300 microgram/kg/min. The infusions lasted for 2 hours and were flanked by both baseline and recovery periods. There was a significant effect of placebo on urinary sodium and chloride excretion rates but no effect on urine flow rate. In response to anaritide, the urine flow rate increased at 0.03, 0.06, 0.075, and 0.100 microgram/kg/min. The sodium and chloride excretion rates increased at all doses except the highest dose. There was no definite effect of anaritide on urinary potassium, calcium, and phosphate excretion rates. There was also no significant effect on creatinine clearance. The mean arterial pressure decreased in response to the 0.060, 0.075, and 0.100 microgram/kg/min doses. In addition, five of the patients receiving the highest dose (0.300 microgram/kg/min) had decreases in their systolic pressures to 90 mm Hg or less. In conclusion, anaritide is natriuretic and diuretic in patients with cirrhosis complicated by ascites and/or edema. Its effect, however, on arterial pressure may limit its therapeutic potential in this patient population.
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PMID:Renal and hemodynamic effects of atrial natriuretic peptide in patients with cirrhosis. 213 74

The cysteinyl leukotrienes C4 and D4 are potent renal vasoconstrictors which may modulate glomerular function in vivo, and may therefore be important in the pathogenesis of hepatorenal syndrome. Urinary leukotriene E4, the major metabolite of leukotrienes C4 and D4, was elevated in patients with hepatorenal syndrome (17.8 ng/h) when compared with normal controls (5.1 ng/h) or subjects with renal failure alone (1.9 ng/h). Urinary leukotriene E4 was also elevated in subjects with decompensated liver disease (cirrhosis with ascites 28.6 ng/h, severe hepatocellular dysfunction 57.5 ng/h), but normal in compensated liver disease (6.7 ng/h). In the early stages of hepatorenal syndrome, leukotriene E4 excretion rate was up to 100-fold higher (560 ng/h) than in normals, and fell in parallel with creatinine clearance, indicative of the glomerular filtration rate-dependent renal excretion. Following correction for creatinine clearance, leukotriene E4, excretion was considerably higher in hepatorenal syndrome (54.1 pg/ml creatinine clearance) compared with normals (1.0 pg/ml creatinine clearance), chronic renal failure (3.2 pg/ml creatinine clearance), decompensated liver disease (ascites 7.7 pg/ml creatinine clearance, and severe hepatocellular dysfunction 11.0 pg/ml creatinine clearance), and compensated liver disease (1.9 pg/ml creatinine clearance). To interpret the significance of these findings, we determined renal clearance and endogenous metabolism of the cysteinyl leukotrienes by infusion of [3H]leukotriene C4 into a single subject with hepato-renal syndrome and two control subjects. Renal clearance of leukotriene E4, was reduced in hepatorenal syndrome (2.4 ml/min) compared with controls (greater than 17 ml/min) which together with the increased excretion rate of leukotriene E4 demonstrates that there is increased cysteinyl leukotriene production in hepatorenal syndrome. This may be one of the factors involved in its pathogenesis.
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PMID:Increased production of cysteinyl leukotrienes in hepatorenal syndrome. 217 35

Factors controlling glucose metabolism after IV load were studied in nine patients with compensated cirrhosis and in six age-matched controls. The time courses of glucose, insulin, and C peptide were analyzed by means of the minimal model technique. In cirrhosis, insulin sensitivity was reduced by approximately 70% and glucose-dependent glucose uptake (glucose effectiveness) by 45%. Decreased glucose effectiveness explained 65% of the variance of glucose disappearance and correlated with the ratio of urinary creatinine to height, an independent measure of muscle mass (r = 0.839). beta-cell responsiveness to glucose, measured on C-peptide kinetics, was variable and increased on average by 170% and 107% (first-phase and second-phase, respectively). The total amount of insulin secreted by beta-cells in the course of the study was nearly doubled, whereas the basal insulin secretion rate was in the normal range. The time courses of hepatic extraction of insulin did not differ between groups, and basal extraction was on average 58% in controls and 56% in patients with cirrhosis. It was reduced to 30% in a single patient who had severe hepatocellular failure and large spontaneous portosystemic shunting. We conclude that the alterations in glucose metabolism of cirrhosis include a decreased insulin sensitivity, a reduced glucose effectiveness, and an increased pancreatic responsiveness to glucose, leading to hyperinsulinemia. The hepatic extraction of insulin is reduced only in the very advanced stages of the disease, possibly because of a large reserve capacity of the hepatic parenchyma.
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PMID:Glucose disposal, beta-cell secretion, and hepatic insulin extraction in cirrhosis: a minimal model assessment. 222 85


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