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  • Articles: DFG German National Licenses  (4)
  • Liver disease  (2)
  • Natriumresorption  (2)
  • 1
    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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  • 2
    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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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 316 (1970), S. 238-258 
    ISSN: 1432-2013
    Keywords: Human Salivary Main Duct ; Transepithelial Electrical Potential Difference ; Salivary Secretion ; Resorption of Sodium ; Secretion of Potassium ; Speicheldrüsengang des Menschen ; Transepitheliale elektrische Potentialdifferenz ; Speichelsekretion ; Natriumresorption ; Kaliumsekretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The electrical potential difference (PD) across the main duct epithelium of the salivary glands was measured in human volunteers. In the resting gland the PD was 38±3 mV, lumen negative. After stimulation of secretion by pilocarpine the PD increased to about 100 mV (lumen negative) and returned to the resting level when secretion ceased. The same increase of PD was observed, when saliva was collected during stimulation and infused back into the duct during the resting state. From this it was concluded that pilocarpine had no direct action on the duct epithelium and that the increase of PD was caused by the changes that are known to occur in salivary electrolyte concentrations during stimulation. This conclusion was tested by perfusion of the duct with different test solutions, so that the influence of single cations and anions on the PD could be studied. With sulfate solutions it was found that the luminal surface of the epithelium behaved like a Na-electrode; a tenfold change of Na-concentration developed nearly 61 mV while K and choline did not affect the PD. Thus the luminal cellwall appears to be selectively permeable to Na. When the duct was perfused with chloride solutions the PD was found to follow a typical time course with the initial transient values yielding a slope of 61 mV and the steady state values a slope of 35 mV for a tenfold change of Na-concentration. This observation can be explained when chloride acts as a shunt ion and when the chloride concentration within the epithelium, which determines the chloride conductance, follows the luminal chloride concentration with a time delay. From the Na und K concentrations of saliva found previously during stop flow experiments and from the present PD measurements it was concluded that the human salivary main ducts, like those of the rat, actively reabsorb Na from the saliva and probably also actively secrete K into the saliva. The localization of the single active and passive transport steps with respect to the luminal and contraluminal cell side is discussed on the basis of Ussing's model for Na transport across frog skin, in favour of which new evidence can be put forward.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 316 (1970), S. 213-237 
    ISSN: 1432-2013
    Keywords: Human Salivary Glands ; Salivary Cation Excretion ; Sodium Reabsorption ; Potassium Secretion ; Speicheldrüsen des Menschen ; Kationenausscheidung ; Natriumresorption ; Kaliumsekretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human saliva was collected separately from the three major salivary glands by catheterization of the main ducts and the effect of secretion rate on salivary Na and K concentrations was studied. In the resting state, with flow rates of 0.1 to 0.4 ml/min, Na concentration of submandibular and parotid saliva was 2 meq/l and K concentration ∼20 meq/l. Similar data were obtained from the resting sublingual gland. Following stimulation with pilocarpine salivary Na concentrations rose in all glands in a typical nonlinear fashion, whereas K concentrations declined and reached constant values, which were significantly greater than those of plasma. This result confirms earlier observations in the submandibular and parotid gland of human beings and of various animals and demonstrates unequivocally that the sublingual saliva in man unlike that in cat and dog is poor in Na. By means of microanalytical methods it was possible to investigate changes in cation concentrations when the salivary flow rates were less than the normal resting values; experiments were also done when salivary flow was stopped completely. In the submandibular gland Na concentration remained at 1.4 meq/l, whereas K concentrations rose to values of 74 meq/l. K concentrations, however, did not reach a plateau value even after a contact time of 15 min. These results, together with measurements of transepithelial P.D. (reported in the following paper), indicate that Na resorption and probably also K secretion, are governed by active transport mechanisms in the duct epithelium. Thus the main duct epithelium exhibits the properties which are generally taken to be essential for the upper part of the glandular duct system, which forms final saliva from primary secretion. Similar data were obtained in the upper portion of the parotid duct. In the lower portion of this duct, however, cation concentrations followed a different pattern in showing a tendency to equilibrate with plasma. Such results would be expected if there were no mechanisms for active transport in the lower portion of the main parotid duct. In order to describe the salivary Na concentration as a function of flow rate a mathematical model was developed. It is based on the assumption that primary secretion is plasmalike and that the hypotonicity of final saliva results from active resorption of sodium in the duct system in accordance with Thaysen's hypothesis. Furthermore the rate of sodium resorption is assumed to be constant and the duct wall is considered impermeable to water. Under conditions of high salivary flow rates there was a good agreement between predicted values and experimental data. This model permits the calculation of the amount of sodium that is actively reabsorbed in the salivary duct system.
    Type of Medium: Electronic Resource
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