E. Fritschka

Different effects of furosemide on alpha-adrenoceptors and on platelet aggregation in man

SummaryThe effect of a long-term administration of furosemide (2×30 mg/day for 3 weeks) on platelet α2-adrenoceptor density and the fraction of high-affinity binding sites, as well as on platelet aggregation induced by adrenaline and ADP, was studied ex vivo in 8 normotensive volunteers. For comparison the in vitro effect of furosemide on platelet aggregation was also evaluated. Furosemide decreased α2-adrenoceptor-density (P<0.01) and the fraction of high-affinity binding sites (P<0.05). Adrenaline-induced platelet aggregation was not altered ex vivo and in vitro. Furosemide inhibited ADP-induced platelet aggregation ex vivo (P<0.05) and in parallel in vitro (P<0.01) in a dose-dependent manner. The reduction of the density of α2-adrenoceptors in the high affinity state may be of functional importance for the hemodynamic effects of furosemide. The inhibitory effect of furosemide on ADP-induced platelet aggregation ex vivo and in vitro, which is not related to the effects on adrenoceptors, seems to involve direct effects of furosemide on platelet function. It remains to be seen whether the latter effect is of clinical importance.

Effect of Fludrocortisone on Adrenoceptors and Free Intracellular Calcium in Man

The mineralocorticoid - induced blood pressure increase in normotensive man is characterized by an early rise in cardiac output during the 1st week of steroid administration and a persistent increase in total peripheral resistance (TPR), which is observed later on, when cardiac output returns to pretreatment values [1,2]. The initial rise in cardiac output has been linked to sodium and volume retention [3,4]. The mechanism of the persistent increase in TPR in the presence of a normal or subnormal cardiac output remains elusive. Alterations of sympathetic nervous system activity and increased passive membrane permeability for sodium have been observed in animal models of mineralocorticoid hypertension [5, 6]. The present study examined parameters of sympathetic activity and intracellular calcium concentration, which ultimately should be linked to altered cellular sodium transport [7] in normotensive volunteers, in whom a mineralocorticoid-induced blood pressure increase was evoked by oral administration of fludrocortisone.

Pharmakologie und antihypertensive Wirksamkeit der Kalziumantagonisten

Fur die Praxis stehen Kalziumantagonisten vom Dihydropyridin-, Verapamil- und Diltiazemtyp mit sehr unterschiedlichen pharmakokinetischen Eigenschaften zur Verfugung. Der Zeitpunkt der maximalen Plasmaspiegel nach oraler Einnahme reicht von 0,5–1 h bis zu 8–9 h. Die Plasmahalbwertszeiten liegen zwischen 2–3 h und 35–50 h. Einige Kalziumantagonisten liegen sowohl in rasch resorbierbarer als auch in retardierter Form vor.

Klinische Pharmakologie II

1963 beschrieb Ommaya ein subkutanes Plastikreservoir, das nach Implantation unter die Kopfhaut einen direkten, sterilen, wiederholbaren Zugang zum Ventrikelliquor ermoglichte. Nach okzipitaler Bohrlochtrepanation des Schadels wurde ein Siliconkatheter in das Hinterhorn des Seitenventrikels eingefuhrt und an das Reservoir angeschlossen.