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 sensory modalities of taste and smell were evaluated in eight patients with cirrhosis that was proved by biopsy specimens and in 13 control subjects. Additionally, the following serum levels were determined in these same subjects: zinc, copper, magnesium, calcium, manganese, and selenium. Fourteen concentrations each of sucrose, sodium chloride, urea, and hydrochloric acid were used to evaluate taste acuity. Smell was evaluated with 11 concentrations each of nitrobenzene, thiophene, and pyridine. These studies show that decreased acuity of taste and smell occurred in conjunction with cirrhosis in the patients who were tested. There were no trace element abnormalities that consistently correlated with decreased acuity in perception of the individual test substances.
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PMID:Decreased taste and smell acuity in cirrhosis. 64 37

The present study was designed to compare the pharmacokinetic handling of a single oral dose of nicardipine in normal subjects and in patients with hepatic cirrhosis and to compare the sensitivity of the two groups to its hypotensive effect. Nicardipine plasma concentrations were substantially higher in the subjects with hepatic cirrhosis with impaired antipyrine clearance, as shown by a significantly higher average Cmax and AUC. The terminal elimination half-life in this group varied from 0.8 to 60.2 hours (median, 11.7 hours), compared with 0.6 to 4.1 hours (median, 1.4 hours) in the group of eight subjects with normal liver function. In the cirrhotic patients with impaired antipyrine clearance, the AUC of the pyridine metabolite averaged 10% of that of the parent drug, whereas in normal subjects the ratio averaged 48%. This finding suggests less conversion of nicardipine to this metabolite in subjects with impaired hepatic function. Peak blood pressure decreases were greater in the cirrhotic group, which was in keeping with the higher plasma levels in these subjects.
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PMID:The effect of hepatic cirrhosis on the pharmacokinetics and blood pressure response to nicardipine. 232 54

Nitrendipine [3-ethyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine dicarboxylate] is a calcium antagonist with a dihydropyridine structure that has a great structural resemblance to nifedipine. Instead of a methyl group in position 3, it has an ethyl group and the NO2 group is in the meta instead of in the ortho position. These minor structural differences have a pronounced impact with respect to both the pharmacokinetics and pharmacodynamics of nitrendipine as compared to nifedipine. Based on equimolar plasma concentrations, nitrendipine is on average three times more potent than nifedipine with regard to the reduction of peripheral vascular resistance, arterial blood pressure, and increased leg blood flow. The terminal half-life is on average 8 h, and thus substantially longer than the terminal half-life of 2-3 h for nifedipine. Despite its almost complete absorption, bioavailability is on average 15-25% and shows great interindividual variability ranging from 7 to 40%. The systemic plasma clearance of the drug is on average 18 ml/min/kg and thus approaches the liver blood flow. In patients with liver cirrhosis, the half-life is prolonged to 19.6 h, the total plasma clearance is decreased by 50%, and the bioavailability is more than doubled to 54%. No data are available if liver disease alters the pharmacodynamic response of the drug. Kidney disease has some effect on the disposition of the drug. Systemic clearance is not changed but the terminal elimination half-life is slightly prolonged to 10.5 h. This increase in half-life is due to an increased volume of distribution. Bioavailability, which is 21.2%, is not grossly altered in renal failure.
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PMID:Pharmacokinetics and pharmacodynamics of nitrendipine in healthy subjects and patients with kidney and liver disease. 246 76

In a controlled double-blind randomized clinical trial, the pharmacodynamics and pharmacokinetics of 20 mg torasemide (1-isopropyl-3-([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) (n = 10) and 40 mg furosemide (n = 9) were compared over 24 h after single oral administration to patients with ascites due to cirrhosis of the liver. The overall 24-h excretion of volume and sodium was not significantly different between patients receiving torasemide or furosemide. The diuretic effect of torasemide, however, was longer in duration than that of furosemide. This was in accordance with the pharmacokinetic behaviour of torasemide and furosemide. The serum elimination half-life of torasemide was longer (4.8 h) than that of furosemide (2.2 h) in these patients and also longer than that in healthy volunteers (3 h). The areas under the serum concentration-time curves for torasemide were higher than in healthy subjects by a factor of 2.5. In parallel with the considerably delayed formation of the diuretically inactive metabolite M5, which is formed via the diuretically active metabolite M1, the serum concentration of M1 was increased in these patients. However, the overall excretion of torasemide and the different metabolites was similar compared to healthy volunteers. These results indicate that the pharmacokinetics and metabolism of torasemide depend on liver function. No adverse reaction were experienced in either group.
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PMID:Comparison of diuretic effects and pharmacokinetics of torasemide and furosemide after a single oral dose in patients with hydropically decompensated cirrhosis of the liver. 328 30

The pharmacodynamics of torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea), a new potent loop diuretic, were compared to those of furosemide in a double-blind controlled study in 18 patients with oedema of various origin. Torasemide behaved like furosemide in exerting a potent diuretic effect which culminated during the first 4 h after its administration. Nevertheless, torasemide was about 8 times more potent, exerted a longer lasting diuretic effect and was more potassium sparing than furosemide. Torasemide did not accumulate during repeated administration (5 days). It was well tolerated and efficient in the treatment of oedema due to congestive heart failure and hepatic cirrhosis. The long duration of action and the potassium sparing effect of torasemide compared to furosemide are promising features of this new potent loop diuretic.
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PMID:Comparative pharmacodynamics of torasemide and furosemide in patients with oedema. 328 31

A choline-deficient L-amino acid-defined (CDAA) diet led to the development of liver cirrhosis in 100% of male Wistar rats after 16 weeks. In contrast, an ordinary (semipurified) choline-deficient (CD) diet led to the development of liver cirrhosis in only 33.3%. After 16 weeks, the liver hydroxyproline content, which reflects the amount of collagen, increased to a level more than four times higher in rats fed a CDAA diet than in rats fed a choline-supplemented L-amino acid-defined (CSAA) diet. Concurrent administration of a prolyl 4-hydroxylase inhibitor, 2,4-pyridine dicarboxylic acid bis(2-methoxyethyl amide) (HOE 077), to rats fed a CDAA diet reduced this increase in liver hydroxyproline content in a dose-dependent manner for doses up to 200 p.p.m. Microscopically, reduction in the hydroxyproline content of the liver resulted in a reduced number of pseudolobuli and thinner fibrous septa. HOE 077 showed no effect on liver hydroxyproline content in rats fed a CSAA diet. The administration of a CDAA diet for 16 weeks led to a substantial induction of GSTP-positive lesions in the liver. The concurrent administration of HOE 077 reduced the number, average diameter and percent area of GSTP-positive lesions in a dose-dependent manner, in parallel with the reduction in hydroxyproline content. These data suggest that inhibition of fibrosis may limit the development of subsequent neoplasms.
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PMID:Prevention of fibrosis reduces enzyme-altered lesions in the rat liver. 795 54

In this study, serum Zn(2+) content was determined by a new enzymatic method. The method depends on the reactivation of apocarbonic anhydrase proportional to the Zn(2+) content of the sample. Carbonic anhydrase was purified from bovine erythrocytes by affinity chromatography. The Zn(2+) in its structure was removed by dialysis against pyridine 2,6-dicarboxylic acid, resulting in a pure apoenzyme with a yield of 100%. The activity of the enzyme was determined by its esterase effect on 4-nitrophenyl acetate. Zn(2+) levels were determined in the serum samples obtained from 100 healthy subjects, 10 patients with cirrhosis, 12 diabetic patients and 15 patients with chronic renal failure by this enzymatic method and by atomic absorption for comparison. There was a good correlation between the two methods in all patients and controls and intraassay CV% was 2.4 and 4.2 for enzymatic and atomic absorption methods, respectively and interassay CV% as 3.9 and 6.1 respectively.
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PMID:An enzymatic method for zinc determination in serum. 834 75

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of torsemide are reviewed. Torsemide belongs to the pyridine-sulfonylurea class of loop diuretics. Its primary site of activity is the thick ascending limb of the loop of Henle, where it blocks active reabsorption of sodium and chloride, resulting in diuresis, natriuresis, and other effects. Torsemide has high bioavailability, a relatively long half-life, and a prolonged duration of activity. It is highly protein bound. Clinical trials indicate that torsemide is effective in the treatment of hypertension and of edema and other symptoms in patients with chronic renal failure (CRF), hepatic dysfunction, or congestive heart failure (CHF). Torsemide has infrequent, mild, and transient adverse effects; among the most common are orthostatic hypotension, fatigue, dizziness, and nervousness. The recommended initial oral dosages of torsemide are 10-20 mg/day for CHF, 20 mg/day for CRF, 5 mg/day for hypertension, and 5-10 mg/day (in combination with a potassium-sparing diuretic or aldosterone antagonist) for hepatic cirrhosis. In most patients, the pharmacokinetic advantages of torsemide over other loop diuretics are unlikely to translate into a substantial edge in clinical outcomes, and in practice there may be no cost advantages. Although torsemide does not offer major advantages over other loop diuretics, it may be of benefit in patients who do not respond to or cannot tolerate other agents.
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PMID:Torsemide: a new loop diuretic. 852 33

A choline deficient L-amino acid defined (CDAA) diet led to the development of liver cirrhosis in male Wistar rats after 16 weeks. A new prolyl 4-hydroxylase inhibitor, 2,4-pyridine dicarboxylic acid bis [(2-methoxyethyl amide)] (HOE 077), prevented liver fibrosis in a dose-dependent manner without a reduction in increased serum alanine aminotransferase and aspartate aminotransferase in parallel with a reduction in preneoplastic enzyme-altered lesions stained with anti-glutathione S-transferase placental form antibody. HOE 077 reduced the increase in serum procollagen III peptide (PIIIP) in a dose-dependent manner and in proportion to the reduction in mRNA expression of type III procollagen in the liver of rats fed a CDAA diet.
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PMID:New prolyl 4-hydroxylase inhibitor reduces procollagen gene expression and enzyme-altered lesions in rat liver cirrhosis. 858 46

The proton pump inhibitor pantoprazole is a substituted benzimidazole sulphoxide for the treatment of acid-related gastrointestinal diseases such as reflux esophagitis, duodenal and gastric ulcers. Pantoprazole, administered as a 40 mg enteric coated tablet, is quantitatively absorbed. Its absolute bioavailability is 77% and does not change upon multiple dosing. Following a single oral dose of 40 mg, Cmax is approximately 2.5 mg/l, with a tmax of 2-3 h. The AUC(O,inf.) is approximately 5 mgxh/l. Pantoprazole shows linear pharmacokinetics after both i.v. and oral administration. Pantoprazole is extensively metabolized in the liver, has a total serum clearance of 0.1 l/h/kg, a serum elimination halflife of about 1.1 h, and an apparent volume of distribution of 0.15 l/kg. 98% of pantoprazole is bound to serum proteins. Elimination half-life, clearance and volume of distribution are independent of the dose. The main serum metabolite is formed by demethylation at the 4-position of the pyridine ring, followed by conjugation with sulphate. Almost 80% of an oral or intravenous dose is excreted as metabolites in urine; the remainder is found in feces and originates from biliary secretion. The pharmacokinetics of pantoprazole are unaltered in patients with renal failure. In patients with severe liver cirrhosis, the decreased rate of metabolism results in a half-life of 7-9 h. The clearance of pantoprazole is only slightly affected by age, its half-life being approximately 1.25 h in the elderly. Concomitant intake of food had no influence on the bioavailability of pantoprazole. Pantoprazole showed lack of cytochrome P450 interaction with concomitantly administered drugs in any of the studies conducted to date. Lack of interaction was also demonstrated with a coadministered antacid. The absence of inductive effects on metabolism after chronic administration was first shown by using antipyrine as a probe for mixed functional oxidative cytochrome P450 enzymes. Absence of CYP1A2 induction was confirmed using the specific probe caffeine. As sensitive probes for CYP3A enzyme induction, urinary excretion of D-glucaric acid and 6 beta-hydroxycortisol were also unchanged.
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PMID:Pharmacokinetics of pantoprazole in man. 873 54


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