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)

Famotidine is a potent histamine H2-receptor antagonist widely used in the treatment and prevention of peptic ulcer disease. After intravenous administration the plasma famotidine concentration-time profile exhibits a biexponential decay, with a distribution half-life of about 0.18 to 0.5h and an elimination half-life of about 2 to 4h. The volume of distribution of the drug at steady-state ranges from 1.0 to 1.3 L/kg; plasma protein binding is low (15 to 22%). Famotidine is 70% eliminated unchanged into urine after intravenous administration. The total body and renal clearances of famotidine correlate significantly with creatinine clearance. Because its renal clearance (15 L/h) far exceeds the glomerular filtration rate, famotidine is considered to be eliminated not only via glomerular filtration but also via renal tubular secretion. Since its clearance is reduced in patients with renal insufficiency and in elderly patients, the maintenance dosage should be reduced in these patient groups. Removal of famotidine by any of the currently employed blood purification procedures (haemodialysis, peritoneal dialysis and haemofiltration) does not occur to a clinically significant degree. Liver cirrhosis does not appear to affect the disposition of famotidine unless severe renal insufficiency coexists. After oral administration, peak plasma concentrations are attained within 2 to 4h; the oral bioavailability ranges from 40 to 50%, due mainly to incomplete absorption. The oral absorption of the drug is dose-independent within a range of 5 to 40 mg. There are 3 formulations available (tablet, capsule and suspension), which appear to be bioequivalent. Coadministration of potent antacids reduces the oral absorption of famotidine by 20 to 30%. On a weight-to-weight basis, the antisecretory effect of famotidine is about 20 and 7.5 times more potent than those of cimetidine and ranitidine, respectively. Plasma famotidine concentrations correlate with its antisecretory effect: values of about 13 and 20 micrograms/L produce a 50% reduction in the gastrin-stimulated gastric acid secretion and a fasting intragastric pH of greater than 4, respectively. Available data suggest that famotidine interacts neither with the hepatic oxidative drug metabolism nor with the tubular secretion of other commonly used therapeutic agents. However, further studies are required to evaluate a full spectrum of its drug interaction potential.
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PMID:Clinical pharmacokinetics of famotidine. 176 69

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 effects of hepatic disease on the pharmacokinetics of the histamine H2-receptor antagonist famotidine were studied in seven healthy volunteers and 20 patients with chronic liver disease. The acute effects of famotidine on hepatic hemodynamics were studied in six healthy volunteers and eight patients with chronic liver disease, and its long-term effects on peptic ulcer, portal blood flow, and hepatic function were studied in 34 patients with chronic liver disease and peptic ulcer. Famotidine clearance was reduced only in patients with decompensated cirrhosis, probably because of concomitant renal impairment. Infusion of 20 mg of famotidine did not reduce hepatic or portal blood flow in healthy subjects, nor did it reduce the gradient between wedged hepatic vein pressure and free hepatic vein pressure or hepatic and portal blood flow in patients with chronic liver disease. An oral dose of 20 mg of famotidine twice daily for two months healed the peptic ulcers in 33 of 34 patients (97%) with chronic liver disease without altering portal blood flow and hepatic function. Even in patients with decompensated cirrhosis, famotidine did not change hepatic function. Thus, famotidine had no effect on hepatic hemodynamics or function in healthy subjects and patients with chronic liver disease. The drug was shown to be well tolerated and effective in the treatment of gastric and duodenal ulcer associated with chronic liver disease.
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PMID:Effects of hepatic disease on the pharmacokinetics of famotidine and effects of famotidine on hepatic hemodynamics and peptic ulcer. 221 Jun 13

The pharmacokinetics of famotidine were studied following single oral and intravenous 20-mg dose administration and after multiple oral 40-mg doses in 11 patients with alcohol-related cirrhosis of varying severity and in five healthy control subjects. No significant differences were observed, following single intravenous administration, in mean plasma famotidine half-lives or in mean plasma famotidine clearance values between the cirrhotic and control groups. Equally, values for mean maximum plasma famotidine concentrations and for mean times to peak plasma concentrations, estimated following single oral administration, were comparable between the groups. The mean (+/- s.d.) systemic availability of the drug, estimated from the areas under the curves, was 36 +/- 24% in the control subjects and 46 +/- 24% in the patients with cirrhosis. No significant increases were observed in trough plasma famotidine concentrations following multiple oral doses in the patients with cirrhosis and there was no evidence of drug accumulation. No significant changes were observed in psychometric performance in any of the patients or control subjects during the multiple-oral-dose study. Thus no significant changes occur in famotidine disposition in patients with cirrhosis even when their disease is decompensated. No reduction in drug dosage should therefore be necessary in these patients. Famotidine may produce less neurological side effects in patients with liver disease than the histamine H2-receptor antagonists used currently.
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PMID:Famotidine pharmacokinetics following oral and intravenous administration in patients with liver disease: results of a preliminary study. 289 Jan 49

A study of 510 patients in Scotland and northeastern England with histological evidence of alcohol-induced liver disease showed no difference in the age of presentation between males and females. Single men and widowed females were particularly susceptible to alcoholic liver disease. The social class distribution was similar to the population in general. Women were more reluctant to volunteer a history of alcoholism than men, they had a higher incidence of previous psychiatric illness (usually due to alcohol abuse) and they developed liver disease at lower consumption thresholds of alcohol than men. Patients under 40 years of age were more likely to have alcoholic fatty liver and less likely to have active cirrhosis than those over 40. Most often, the presenting symptoms were non-specific and tended to be related to the gastrointestinal system, particularly in women. Five per cent of patients were asymptomatic and 14% came to hospital for conditions other than alcoholic liver disease. Important clues to asymptomatic alcoholic liver disease included hepatomegaly, clubbing of the fingers and abnormal liver function tests. Gastro-oesophageal varices accounted for 40% of instances of haemorrhage and the mortality from upper gastrointestinal bleeding was 17%. Anaemia was the most common haematological abnormality. Alcoholic hepatitis was observed more frequently in the Glasgow area then elsewhere.
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PMID:Alcoholic liver disease in Scotland and northeastern England: presenting features in 510 patients. 660 94

Thoracic varices are rare anomalies in patients with liver cirrhosis and portal hypertension. Gastro-oesophageal varices usually drain into the azygos or hemiazygos vein. The case is reported here of an unusual collateral pathway of gastro-oesophageal varices with drainage to the vena anonyma system presenting as lung masses on chest X-ray, which completely resolved after successful liver transplantation.
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PMID:Unusual thoracic collaterals of gastro-oesophageal varices in a patient with end-stage liver disease. 874 70

A/H1N1/09 influenza is associated with a high risk of complications in patients with chronic diseases, but data on morbidity and mortality in patients with cirrhosis are limited. A cluster of A/H1N1/09 infection in 48 patients admitted to a Gastro-Hepatology Unit is reported. Nosocomial spread, clinical outcome, and viral characteristics of A/H1N1/09 strains from a study group of 48 inpatients (21 and 27 with and without cirrhosis, respectively) were compared with those from a control group of 44 outpatients with mild influenza-like illness and without cirrhosis. A/H1N1/09 infection was confirmed in 8/48 (17%) inpatients. A/H1N1/09 infection rate did not differ in patients with and without cirrhosis (4/21, 19%; 4/27, 15%), but three patients with cirrhosis died of pneumonia and acute respiratory distress syndrome, with fungal or bacterial superinfection in two cases, despite antiviral treatment. None of patients without cirrhosis died. Viral sequences showed the presence of hemagglutinin mutation D222G in two out of three fatal cases and S183P in seven out of eight infected patients. These mutants were not detected in the outpatients group. Even if A/H1N1/09 infection rate in hospitalized patients with and without cirrhosis was not significantly different, cirrhosis and D222G/S183P substitutions were significantly associated with severe disease and poor outcome, also suggesting fungal or bacterial superinfection and portal hypertension as risk factors for A/H1N1/09 disease severity in patients with cirrhosis. Vaccination, preventive and early treatment and a strict control of nosocomial spread should be activated carefully in patients with cirrhosis during epidemics influenza.
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PMID:Clinical impact of A/H1/N1/09 influenza in patients with cirrhosis: experience from a nosocomial cluster of infection. 2315 73