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)

Furosemide is frequently used for ascites and causes adverse reactions (AR). In an intensive prospective drug monitoring study of 1,920 patients, 172 (8.9%) had cirrhosis of the liver and received furosemide. Mean age was 53 years, and 66.3% were male; and 87% had alcoholic cirrhosis. Eighty-eight (51.2%) had 221 events that by consensus of the monitoring team and attending physicians were either definitely of probably related to furosemide. No AR was fatal but 24% of patients had severe reactions. Almost all reactions were dose-related (96%). The most common were electrolyte disturbances (23.3% of patients) and volume depletion (14%). Furosemide-induced coma occurred in 20 (11.6%) patients and was more frequent in patients with prior hepatic encephalopathy (p less than 0.0005). Higher total doses (p less than 0.001), hyerbilirubinemia (p less than 0.05), prolonged prothrombin time (p less than 0.02), and longer hospital stay (p less than 0.001) were associated with higher frequencies of AR to furosemide. The frequency of hypokalemia did not decrease when potassium chloride or potassium-sparing diuretics were added to furosemide therapy. Frequdncy of AR did not correlate with age, sex, renal impairment, serum albumin, transaminase, or alkaline phosphatase.
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PMID:Furosemide-induced adverse reactions in cirrhosis of the liver. 75 67

In an attempt to produce an animal model for the disease cystic fibrosis (CF), mice were treated chronically with the diuretics amiloride and furosemide, in order to cause chronic inhibition of transepithelial ion transport. Experiments were carried out on adult mice (2 months treatment); in addition, pregnant mice were treated with diuretics, and tissue from offspring 2 and 7 days post partum was investigated. Since biliary cirrhosis is a common occurrence in CF, hepatocytes in the treated mice were investigated by X-ray microanalysis and by light and electron microscopy. Treatment with amiloride caused a significant decrease in cellular Na concentration in adult animals and in in utero treated mice 2 days after birth. The decrease in Na was paralleled by a decrease in Cl, but K levels were not affected. Furosemide caused a slight increase of cellular Na concentrations, especially in animals aged 7 days. In the adult animals, both amiloride and furosemide caused a significant decrease of the cellular Na and Cl levels. No signs of cirrhosis could be observed. Inconsistent changes in the accumulation of lipid droplets in hepatocytes of adult animals treated with amiloride were observed by electron microscopy. It can be concluded that chronic treatment with diuretics, even though it causes some, possibly pathological, changes of the liver, is only of very limited value for generating an animal model to study liver disease in CF.
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PMID:Effect of chronic treatment with diuretics on mouse liver: a morphological and microanalytical investigation. 129 84

Daily urine levels of PGE2 and PGF2 alpha as well as water-electrolyte exchange were measured in 72 patients with chronic active hepatitis (CAH) and hepatic cirrhosis (HC) in comparison with healthy controls. Furosemide treatment was performed in 26 HC patients. It was established that in CAH and compensated HC daily excretion of PGE2 and PGF2 alpha as well as 22Na elimination were within the range registered in the control. In association of HC with nonrefractory ascites the above excretion was elevated, with refractory one daily excretion of PGE2 was low, the urine ratio PGF2 alpha/PGE2 rose. Daily urine excretion of prostaglandins and PGF2 alpha/PGE2 value may be of prognostic significance in evaluating efficacy of diuretic therapy in HC patients with ascites.
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PMID:[Effect of furosemide on the renal prostaglandin system in liver cirrhosis with ascites]. 261 14

In patients with cirrhosis, it has been demonstrated that blood volume and degree of portal hypertension are correlated. Hence, a reduction of blood volume by furosemide could decrease portal pressure and could thereby be useful in the treatment of portal hypertension. Splanchnic and systemic haemodynamics were evaluated before and 1 h after intravenous administration of furosemide (0.75 mg/kg) in 10 patients with cirrhosis. Furosemide significantly increased haemoglobin from 12.4 to 13.0 g/dl and patients passed more than 1 l of urine within the 3 h following furosemide administration. These findings confirm that blood volume decreased after diuretic administration. Cardiac output significantly decreased from 6.6 +/- 2.3 to 5.5 +/- 2.2 l/min, while arterial pressure and heart rate did not change significantly. Furosemide significantly decreased wedged hepatic venous pressure from 31.1 +/- 6.2 to 27.7 +/- 5.2 mmHg, but not free hepatic venous pressure. Accordingly, the hepatic venous pressure gradient significantly decreased from 22.1 +/- 5.4 to 19.5 +/- 4.0 mmHg. Azygos blood flow and hepatic blood flow also significantly decreased from 0.40 +/- 0.17 to 0.31 +/- 0.13 l/min and from 1.49 +/- 0.50 to 0.82 +/- 0.30 l/min, respectively. These results show that diuretic therapy markedly influences splanchnic haemodynamics.
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PMID:Reduction of portal pressure by acute administration of furosemide in patients with alcoholic cirrhosis. 280 66

Plasma levels of atrial natriuretic peptide (ANP), aldosterone (PA), vasopressin (AVP), and the plasma renin activity (PRA) were examined in 15 vascularly decompensated patients suffering from liver cirrhosis, before and after administration of albumin and after a subsequent administration of furosemide. The initial ANP level was lower in 9 patients (group "A") and higher in 6 patients (group "B") than in healthy controls (Group "A": 19.5 +/- 3.0 fmol/ml; group "B": 36.7 +/- 3.9 fmol/ml; control: 25.8 +/- 2.4 fmol/ml). The initial PRA (4.4 +/- 1.0 ng AngI/ml/h) and AVP (8.5 +/- 1.5 pg/ml) activity in group "A" increased significantly compared to group "B" (PRA: 0.44 +/- 0.09; AVP: 4.1 +/- 0.5), indicating an intravascular volume depletion in group "A". Albumin infusion raised the urine and sodium excretion and the plasma concentration of ANP in group "A" but lowered in plasma levels of renin and vasopressin. The same parameters were not changed by albumin in group "B". Furosemide equally raised the urine flow rate and sodium excretion in both groups. Plasma ANP level depends on the intravascular volume, and the secondary change in its plasma concentration plays a considerable role in the retention of fluid and electrolytes in patients with cirrhosis. The increased intravascular volume in these patients depletes the fluid and electrolyte retention via the increase in ANP level.
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PMID:Alterations of vasoconstrictor and sodium-regulating hormone systems in vascularly decompensated liver cirrhosis. 297 Jun 21

Factors that influence intersubject variability in response to furosemide have been investigated in normal subjects and patients with cirrhosis. Furosemide pharmacokinetics and pharmacodynamics were measured in eight normal subjects and 14 patients with cirrhosis, eight of whom were resistant to diuretic therapy. Furosemide renal clearance decreased in proportion to creatinine clearance, whereas nonrenal clearance and volume of distribution were unchanged. These pharmacokinetic changes were, however, minimal and resulted in an only marginal alteration in the plasma concentration-time curve. The maximal rate of urinary sodium excretion decreased with reductions in creatinine clearance (r = 0.77). However, the extent of reduction in urinary excretion of sodium was proportionally greater than the reduction in creatinine clearance, whereas the rate of urinary furosemide excretion required to achieve 50% of maximal response did not change. Furosemide's pharmacokinetics were not, therefore, appreciably altered by cirrhosis. However, cirrhosis was associated with a reduction in pharmacodynamic response to this diuretic.
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PMID:Furosemide kinetics and dynamics in patients with cirrhosis. 372 Jan 75

Furosemide disposition after rapid intravenous injection (80 mg) was studied in 10 normal healthy subjects and eight patients with cirrhosis and ascites. In the cirrhotic patients the elimination half-life was modestly longer (81.0 +/- 8.0 min and 60.2 +/- 5.8 min). This prolongation was not associated with a difference in systemic clearance (156 +/- 7 ml/min in normal and 142 +/- 16 ml/min in cirrhotic subjects), rather it was a reflection of alterations in furosemide distribution. The steady-state volume of distribution was increased from 8.5 +/- 0.4 l in the healthy subjects to 12.1 +/- 1.3 l in the cirrhotic subjects; estimation in terms of unbound drug indicated an approximately 50% smaller value in cirrhosis. These observations were quantitatively consistent with the increased percentage of furosemide in plasma in the unbound form in the patients (10.2 +/- 1.0%) compared to in the normal subjects (4.0 +/- 0.1%). The 24-hr percentage urinary recovery of unchanged drug (58.8 +/- 2.8% and 53.1 6.5%) and the glucuronide metabolite (17.8 +/- 1.5 and 21.3 +/- 3.4) were on the same order in the normal and cirrhotic groups. The lack of major effects of cirrhosis on furosemide disposition suggests that changes in furosemide diuretic efficacy in such patients is a result of altered dynamic factors rather than altered disposition.
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PMID:Furosemide disposition in cirrhosis. 707 20

The pharmacokinetics of furosemide was studied in 7 patients with diagnosed liver cirrhosis and in 7 healthy subjects. Furosemide in plasma and ascitic fluid was analyzed spectrofluorometrically. After a single intravenous dose, the cirrhotic patients showed lower initial plasma concentrations of furosemide because of the larger volume of distribution. The mean half-life in cirrhotic patients was significantly greater than in healthy volunteers. The longer half-life was associated with a reduction in the serum clearance of furosemide. Ascitic fluid volume in the patients ranged from 4.6 to 7.71. There was no significant amount of furosemide in the fluid. The diuretic interchange between this fluid and plasma was slow, as peak concentrations ranged from 0.3 to 0.5 microgram/ml within 3 to 5 h after bolus administration of furosemide. Diuresis and urinary sodium excretion, 5 h after furosemide injection, were similar in both groups; larger potassium excretion was found in the cirrhotic patients.
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PMID:Pharmacokinetics of furosemide in patients with hepatic cirrhosis. 710 67

Frusemide 80mg was administered intravenously to 10 patients with alcoholic liver disease (fatty liver and Laemnec's cirrhosis). Protein binding was correlated with serum albumin concentrations (r = 0.860, p < 0.001). The apparent volume of distribution ranged between 180 and 1206ml/kg body weight and correlated with the serum albumin concentration (r = 0.710, p < 0.05) and the fraction of unbound drug (r = 0.758, p < 0.05). This fraction was 1.9 +/- 0.2% in controls and 3.1 +/- 0.9% in patients with cirrhosis (p < 0.01). Plasma half-life of frusemide varied 7-fold, between 0.60 and 4.27h, and was prolonged substantially in some patients compared with values in normal subjects. There was a highly significant correlation between the apparent volume of distribution and plasma half-life of frusemide (r = 0.938, p < 0.001). Frusemide was eliminated via both renal and non-renal mechanisms in all but 2 patients, who had advanced cirrhosis and eliminated the drug almost exclusively though the kidneys. The apparent volume of distribution was increased proportionally more than the decrease in protein binding explaining in part why higher doses of frusemide are needed in patients with liver disease to obtain the same response as in healthy subjects.
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PMID:Frusemide pharmacokinetics in patients with liver disease. 743 54

The influence of cimetidine on the natriuretic and diuretic responses to furosemide was studied in 10 patients with hepatic cirrhosis. After four days on a low sodium diet, the patients were given 40 mg of furosemide i.v. and from the sixth to the eleventh day they received 400 mg of cimetidine p.o. every 6 h and a second dose of furosemide with the last 6 h dose. Ten healthy subjects received the same dose of furosemide. Multiple blood and urine samples from both groups were analyzed for furosemide, sodium and creatinine. Furosemide kinetics were not affected in patients with hepatic cirrhosis but the effect was lower than in the controls: urinary excretion of sodium (0.47 +/- 0.07 vs 1.59 +/- 0.10 mmol/min, p < 0.05) and urine excretion (4.86 +/- 0.57 vs 9.16 +/- 0.85 ml/min, p < 0.05). The predicted maximal effect of furosemide (Emax) and the furosemide urinary rate of excretion needed to elicit 50% of Emax for the cirrhotic patients and the controls were 1.85 +/- 0.21 and 3.22 +/- 0.41 mmol/min (p < 0.05) and 137 +/- 15 and 99 +/- 12 micrograms/min (p < 0.05), respectively. The amounts of sodium filtered (FNa) and reabsorbed in response to the injection of furosemide were lower in the cirrhotic patients than in the controls, however, relative to the FNa, the cirrhotic patients reabsorbed more sodium than the controls. The administration of cimetidine did not affect the kinetics of furosemide nor its natriuretic or diuretic responses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of effect of cimetidine on furosemide kinetics and dynamics in patients with hepatic cirrhosis. 822 96


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