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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 70 (1992), S. S120 
    ISSN: 1432-1440
    Keywords: Hypertension ; Kidney ; Antihypertensive drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antihypertensive therapy influences kidney function by different mechanisms depending on the mode of action of the drug used. The GFR is improved by calcium entry blockers and ACE inhibitors, unaffected by vasodilators, α-blockers and centrally acting sympatholytics and impaired by β-blockers. The same is true for renal blood flow and is due to changes of renal vascular resistance. Renal sodium excretion is impaired mostly by vasodilators, by α-blockers, sympatholytics and β-blockers; in contrast, calcium entry blockers and ACE inhibitors acutely induce natriuresis. The RAAS is stimulated by vasodilators, unaffected by α-blockers and sympatholytics and suppressed by β-blockers. Plasma catecholamines are stimulated by vasodilators and suppressed by centrally acting sympatholytics and unaffected by the others. Induction of acute renal functional impairment is reported for ACE inhibitors under conditions of compromised renal perfusion pressure such as in renal artery stenosis. These data from the literature reviewed are supported by our own experimental data on sodium balance under different drugs and micropuncture data in experimental renal artery stenosis. To achieve effective antihypertensive treatment with a low profile of side effects, careful monitoring of renal function seems to be mandatory.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 66 (1988), S. 914-919 
    ISSN: 1432-1440
    Keywords: Erythropoietin ; Hypertension ; Erythropoietin ; Hypertonie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Wirksamkeit von rekombinantem humanem Erythropoietin (rhEpo) bei der Korrektur der Anämie des terminal niereninsuffizienten dialysepflichtigen Patienten ist in mehreren Studien belegt. Eine deutliche Verbesserung der physischen Leistungsfähigkeit konnte durch ergometrische Untersuchungen dokumentiert werden. Neben seltenen Shunt-Thrombosen ist die einzige relevante unerwünschte Wirkung von rhEpo die Entwicklung oder Aggravierung einer Hypertonie bei etwa 30% der behandelten Patienten. Bei ca. 2% der Patienten kam es zur hypertensiven Enzephalopathie mit zentralnervöser Symptomatik. Als Ursache für diese Hypertonie-Entwicklung ist ein Anstieg des peripheren Widerstands anzunehmen. Belege dafür sind Messungen des regionalen Blutflusses mit Plethysmographie vor und nach Anämie-Korrektur mit rhEpo. Ursache für den Widerstandsanstieg wiederum dürfte eine Zunahme der Vollblutviskosität und eine Abnahme der peripheren hypoxiebedingten Vasodilatation sein. Zur Prävention der hypertensiven Komplikationen bei rhEpo-Therapie werden eine langsame Hämatokrit-Korrektur über 12–16 Wochen und eine Begrenzung des Ziel-Hämatokrits auf 30–35 Vol. % bei strikter Blutdruck- und Volumenkontrolle empfohlen.
    Notes: Summary Recombinant human erythropoietin (rhEpo) has been demonstrated in several studies to be effective in correcting the anemia of regular dialysis patients. This was accompanied by a significant improvement of the physical work capacity shown by exercise testing. The main side effect of rhEpo treatment has been the development or aggravation of hypertension in approximately 30% of the treated patients. In 2% hypertensive encephalopathy and convulsions occured. Data obtained by measurements of regional blood flow indicate the peripheral resistance did increase probably due to rise of blood viscosity and reversal of preexisting hypoxic vasodilatation. To avoid hypertensive complications anemia should be corrected slowly over a period of 12–16 weeks. Target hematocrit should not exceed 30–35 vol. %. Blood pressure and volume status should be monitored closely.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 279 (1973), S. 211-226 
    ISSN: 1432-1912
    Keywords: Cardiac Glycosides ; Brain ; Behaviour ; Distribution ; Protein Binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats and mice were injected with 3H-labelled β-methyldigoxin, digoxin or digitoxin i.p. Four hours later, the concentrations of radioactivity were measured in the plasma and in skeletal muscle or in the brain. Protein binding in the plasma was determined and the concentration of radioactivity in the plasma water was calculated. By dividing the injected dose or the concentration in the tissue by that in the plasma water, distribution coefficients (DCs) were calculated for the whole body, skeletal muscle and brain. Some extra-cardiac effects of the three glycosides were quantified and the concentrations that may be expected in plasma water, skeletal muscle and brain after the administration of equiactive doses were calculated. 1. The DC of the injected dose was lower for β-methyl-digoxin than for digoxin and digitoxin. This difference cannot be explained by a slow elimination of β-methyl-digoxin suggesting that it has a low distribution volume in these species. 2. In rats, the DC between skeletal muscle and plasma water decreased in the order digitoxin 〉 digoxin ≫ β-methyl-digoxin. 3. In mice and rats, the DC between brain and plasma water decreased in the order digitoxin ≫ β-methyl-digoxin 〉 digoxin. 4. Protein binding decreased in the order digitoxin ≫ digoxin 〉 β-methyldigoxin. 5. In rats, the doses producing an equal increase in potassium excretion decreased in the order digitoxin 〉 digoxin 〉 β-methyl-digoxin. On the other hand, the concentrations of radioactivity in the plasma water correlated with these doses decreased in the order β-methyl-digoxin 〉 digitoxin ≫ digoxin. There was no significant difference between the intracellular concentrations of digoxin and β-methyl-digoxin in skeletal muscle. 6. In mice, there was no clear correlation between inhibition of spontaneous motility or righting reflexes on the rotating rod and the concentrations of radioactivity in the plasma water or in the brain. β-Methyl-digoxin is moee lipophilic than digoxin but it penetrates less into skeletal muscle. It is as lipophilic as digitoxin, but it penetrates less into the brain of rats and mice. This shows that penetration of the cell membrane by cardiac glycosides does not solely depend on lipid solubility.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 302 (1978), S. 87-90 
    ISSN: 1432-1912
    Keywords: Cats ; Cardiac glycosides ; Brain ; Distribution ; Side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The tissue/plasma ratio of β-methyl-digoxin for cardiac muscle in cats was about the same 24 h after a single dose of 30 μg/kg as after a loading dose of 30 μg/kg followed by 3 maintenance doses of 7.5 μg/kg at 24 h intervals. The ratio for the brain increased 2-fold during that time. After the i.v. injection of a toxic loading dose of 70 μg/kg β-methyl-digoxin or digoxin, maintenance doses of as little as 15 μg/kg at 48 h intervals sufficed to maintain the minimum plasma glycoside concentrations determined by RIA at about 3 ng/ml. There was no difference in the plasma concentrations or in the severity of intoxication produced by both glycosides. Cats vomited within 3 h after i.v. injection of 100 μg/kg β-methyl-digoxin, whereas a loading dose of 30 μg/kg followed by 3 injections of 7.5 μg/kg at 24 h intervals were well tolerated. The concentration of radioactivity in the brain 3 h after 100 μg/kg was less than 24 h after the last injection of 7.5 μg/kg in the experiments with repeated dosage. Cerebral side-effects such as vomiting, loss of appetite and weight were better correlated with the glycoside concentrations in the plasma than with those in the brain.
    Type of Medium: Electronic Resource
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