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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 233 (1982), S. 432-436 
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Nuclear Inst. and Methods in Physics Research, B 63 (1992), S. 227-230 
    ISSN: 0168-583X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 69 (1991), S. 239-250 
    ISSN: 1432-1440
    Keywords: Diuretics ; Pharmacokinetics ; Renal failure ; Liver disease ; Congestive heart failure ; Nephrotic syndrome ; Dose response relationship ; Resistance to diuretics ; Combination therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diuretics are classified according to their site of action in the nephron: loop diuretics, thiazides, and antikaliuretics. During peak diuresis the pattern of electrolyte excretion is constant and characteristic for a class of diuretics. The ratio of diuretic-induced excretion of K+ to Na+ is 0.12 for loop diuretics, 0.20 for thiazides, and −0.21 for antikaliuretics. The ratio of Ca2+ to Na+ is 0.02 for loop diuretics and 0.003 for thiazides. Mg2+ excretion follows K+ excretion in a ratio of 0.15. The natriuretic effect of a diuretic directly depends on the renal clearance of the drug and is proportionate to the number of intact nephrons. Not only loop diuretics but also thiazides and antikaliuretics were demonstrated to be effective natriuretic drugs down to end-stage renal disease. In renal failure FENa is doubled with every halfening of GFR. Loop diuretics increase FENa to a maximum of 24%, thiazides to 10–15%, and FENa is doubled by antikaliuretics. Comedication of loop diuretics with thiazides in renal failure may therefore be more effective than increasing monotherapy. In liver disease, nonrenal drug clearance is reduced the more the patient's direct bilirubin rises thus causing an increase in AUC and urinary excretion of parent drug and metabolites. Despite increased Ae, the cirrhotic patient may become resistant to diuretics as may patients with congestive heart failure or nephrotic syndrome. This is considered to be due to reduced Na+ load available at the diuretic's site of action following avid proximal Na+ reabsorption. In reduced EABV a short-term comedication of loop diuretics with carboanhydratase inhibitors is considered a more effective diuretic strategy than vigorously increasing monotherapy.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1440
    Keywords: Ascites ; Liver cirrhosis ; Xipamide ; Spironolactone ; Furosemide ; Resistance to diuretics ; Fractional sodium excretion ; Side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a randomized prospective study the efficacy and side effects of xipamide versus the combination spironolactone/furosemide in the treatment of cirrhotic ascites were studied. Out of 27 patients four responded to a basic treatment consisting of salt and water restriction and one had to be excluded because of deterioration of kidney function. The remaining 22 patients were randomized to additional treatment with either 20 mg xipamide/day (group I) or 200 mg spironolactone/ day combined with 40 mg of furosemide every other day (group II). A response to treatment during the first 4 days was seen in 7 of 11 patients of group I versus only 3 of 11 patients in group II. In the latter group 7 of 11 patients finally responded after 8 days of treatment. Responsiveness to either diuretic treatment strongly depended on pretreatment fractional Na excretion, FENa. The resistance to diuretic treatment can be predicted by a FENa〈0.2%, and could be overcome by additional strategies known to reduce avid proximal Na reabsorption. Xipamide frequently induced hypokalemia, whereas hyperkalemia was seen following treatment with spironolactone/furosemide. Kidney function remained stable during either diuretic treatment.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 68 (1990), S. 692-698 
    ISSN: 1432-1440
    Keywords: Gemfibrozil ; Gastric antacids ; Absorption ; Elimination ; Biliary excretion ; Jaundice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The disposition of the lipid-lowering drug gemfibrozil was studied in patients with either renal (n= 8) or hepatic disease (n= 8) and compared to those of healthy volunteers (n= 6). Gemfibrozil was determined in plasma and urine by means of a HPLC method. Urine was also analyzed for gemfibrozil conjugates. Following oral administration of 900 mg gemfibrozil, maximal plasma levels of the parent drug were 46.1±15.8 μg/ml, attained after 2.2±1.1 h. In chronic renal failure and in liver cirrhosis the plasma concentrations of gemfibrozil did not significantly differ from that of controls except in those patients who were comedicated with antacids. These patients had significantly lower Cmax and AUC values. The elimination half-life of the drug was 1.5 h in controls, 2.4 h in renal failure, and 2.1 h in liver disease. In healthy volunteers, only 0.02 to 0.15% of the given dose was recovered in the urine as parent gemfibrozil, while conjugates made up 7–14%. In patients with renal failure also, only traces of parent gemfibrozil could be detected, and conjugates accounted for 0.5–9.8%. In those with liver disease, however, about 0.1–0.2% were recovered in urine as parent gemfibrozil and up to 50% as conjugates. Strikingly, the amount of excreted conjugates in the urine was positively correlated to the direct bilirubin plasma concentration. It can be concluded that the elimination of gemfibrozil is not significantly influenced by renal failure. However, comedication with antacids markedly reduced plasma disposition of the drug. Patients with severe liver disease excreted more conjugated gemfibrozil via the kidney than did healthy controls. Thus, transfer across the canalicular cell membrane to the bile duct, rather than drug metabolization, is primarily disturbed in liver disease. Gemfibrozil accumulation is unlikely to occur in either kidney or liver disease.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 292 (1976), S. 189-192 
    ISSN: 1432-1912
    Keywords: Amiloride ; Ouabain ; Active transport of Na+, K+, H+/HCO 3 - ; Membrane ATPases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The submaxillary duct epithelium, which actively transports Na+ (rabbit) and, in addition, K+ and H+/HCO 3 - (rat), was used as a model epithelium to compare the effects of ouabain and amiloride on transport parameters. 1. Ouabain was only effective from the interstitial side, amiloride, however, only from the luminal side. Amiloride induced effects on transport of the ions were seen within less than 1 s, ouabain effects, however, only after minutes. 2. Ouabain inhibited in a parallel fashion the Na+ transport potential and the Na+−K+-ATPase activity. It had no effect on the Mg2+-ATPase and the HCO 3 - -ATPase. 3. Amiloride also inhibited the Na+ transport potential and the Na+−K+-ATPase; however, the Na+ transport potential was significantly more sensitive to amiloride than the Na+−K+-ATPase. 4. Amiloride inhibited in a similar fashion the Na+−K+-ATPase, the Mg2+-ATPase and the HCO 3 - -ATPase, but did not influence active HCO 3 - secretion. 5. It is concluded that the amiloride induced effects on the membrane ATPases are non-specific.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 60 (1982), S. 1191-1200 
    ISSN: 1432-1440
    Keywords: Solute transport ; Leaky and tight epithelia ; Membrane porter systems ; Transport disorders ; Aminoaciduria ; Glucosuria ; Rickets ; Fanconi syndrome ; Bartter's syndrome ; Renal tubular acidosis ; Diabetes insipidus ; Chloridorrhea ; Stofftransport ; Lecke und dichte Epithelien ; Membrancarrier ; Tubulopathien ; Aminoazidurie ; Glucosurie ; Phosphatdiabetes ; Fanconi-Syndrom ; Bartter-Syndrom ; Renal-tubuläre Azidosen ; Diabetes insipidus ; Chloriddiarrhoe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Epitheliale Strukturen können als „leck“ oder „dicht“ klassifiziert werden entsprechend ihren Eigenschaften beim Salz- und Wassertransport. Sowohl die proximalen Anteile des Nephrons wie auch des Darmtraktes gelten als „leck“, während das distale Nephron und der Dickdarm als „dichte Epithelien“ angesehen werden. Entsprechend dieser Klassifikation manifestieren sich angeborene Störungen des Stofftransportes als auch Defekte durch exogene Noxen meist in analoger Ausprägung sowohl im proximalen Nierentubulus als auch im Dünndarm. Darüberhinaus bestehen große Ähnlichkeiten in der Beeinflußbarkeit und Regulation des Salz- und Wassertransportes des distalen Nephrons wie auch des Dickdarms. In der vorliegenden Übersicht werden Modelle des Stofftransportes durch lecke und dichte Epithelien entwickelt, die auf bekannte in Säugerzellen nachgewiesene Transportsysteme zurückgreifen. Die renalen Tubulopathien als auch die intestinalen Transportstörungen werden auf Defekte der epithelialen Transportsysteme zurückgeführt.
    Notes: Summary Epithelia can be classified as “leaky” and “tight epithelia” due to their conductive properties and their modes of solute transport. Both the proximal segment of the nephron and the intestinal tract are “leaky” whereas the distal nephron and the colon are “tight”. Consequently, inborn errors and exogenous disorders of solute transport often involve both the proximal tubule and the small intestine. In addition, effects on ion and water transport in the distal nephron closely resemble those in the large intestine. Models of solute transport in leaky and tight epithelia are presented employing porter systems known in mammalian tissues. These porter systems are discussed as possible sites of transport defects and as targets for pharmacological agents.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1440
    Keywords: Triamterene ; Pharmacokinetics ; Metabolism ; Bioavailability ; Determination ; Liver disease ; Renal disease ; Age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The knowledge about the pharmacokinetics of triamterene (TA) was limited until recently. The metabolic pathway of TA is the formation of p-hydroxytriamterene (OH-TA), which is subsequently conjugated with active sulfate to form p-hydroxytriamterene sulfuric acid ester (OH-TA-ester). The phase-II-metabolite is surprisingly pharmacologically active. TA and its metabolites were measured concomitantly by a specific and sensitive tlc-method. The i.v. kinetics of TA were determined after application of a newly developed lactic acid solution of the drug. Comparing these data with results after oral application of TA the bioavailability of TA was 52% and the extent of absorption 83%. The bioavailability of different dosage forms was correlated with in vitrotests. In liver disease the pharmacokinetics of TA are markedly altered. While in cirrhosis the hydroxylation of TA was decreased, the biliary excretion of this agent was strongly reduced in hepatitis. In renal disease the excretion of TA and OH-TA-ester was reduced proportional to the reduction of endogenous creatinine clearance. In older patients the elimination of TA was impaired.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 407 (1986), S. S85 
    ISSN: 1432-2013
    Keywords: Rat proximal colon ; Short-circuit current ; Electrical resistance ; Transport of Cl−, HCO 3 − , Na+ and K+ ; Stimulus-secretion coupling ; Secretagogues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transport of electrolytes, particularly of Cl− and K+, by the rat proximal colon was studied in vivo under conditions of high and low K+ diet and in the presence of transport inhibitors and secretagogues. The electrical parameters, PD,I sc,R m, were monitored by direct clamping and via cable analysis. The present work reinforces own earlier work and that of others that — under control conditions — absorption of Na+ and Cl− is mainly electrically neutral. Low K+ diet reduced aborption of Na+ and Cl−, as well as secretion of K+, and increased HCO 3 − absorption. High K+ predominantly increased K+ secretion and reduced HCO 3 − absorption, these diet-induced changes being electrically neutral [17]. Secretagogues such as PGE1 and theophylline reduced net absorption of Na+ and Cl−, increased theI sc and lowered theR m. These effects could be reversed by the antidiarrheal drugs, loperamide and somatostatin, except the increase of K+ secretion, and reversed HCO 3 − transport absorption to secretion. A model consisting of absorptive columnar cells and secreting crypt cells is presented which encompasses the known and supposed aspects of colonic ion transport.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 361 (1975), S. 55-59 
    ISSN: 1432-2013
    Keywords: Active secretion of K+ and HCO 3 − ; Active Na+ reabsorption ; Membrane conductance of Na+ and K+ ; Salivary duct ; Amiloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to elucidate whether or not active secretion of potassium and bicarbonate by the rat submaxillary duct epithelium operates independently of sodium reabsorption, Na+ transport was blocked by amiloride, which is known to inhibit Na+ entry from lumen into cell. With 10−4 M amiloride in HCO 3 − -Ringer at the luminal side, the transepithelial electrical potential difference approached zero, the Na+ conductance of the luminal cell membrane was drastically reduced, and the K+ conductance was significantly reduced. Net K+ secretion was reduced by 80%, whereas net HCO 3 − secretion was significantly increased. The remaining 20% of net K+ secretion proceeded at zero net Na+ transport and in the absence of significant chemical and electrical potential differences between lumen and interstitium of the duct. This active component of net K+ secretion was accompanied by an equal rate of active HCO 3 − secretion. These findings confirm the independence of this active secretion of K+ and HCO 3 − from Na+ transport. They indicate an electrically neutral secretion of K+ and HCO 3 − , probably by the postulated luminal K+−H+-exchange mechanism. The 80% of net K+ secretion, which were abolished by amiloride together with Na+ reabsorption, seem to be functionally coupled with Na+ transport. The linkage of K+-to-Na+ is probably mediated by a luminal carrier exchanging Na+ for K+ and H+.
    Type of Medium: Electronic Resource
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