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  • 1
    Electronic Resource
    Electronic Resource
    Stimulation of aldosterone secretion by metoclopramide is not affected by chronic converting enzyme inhibition (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 207-210 
    Details
    ISSN: 1432-1041
    Keywords: metoclopramide ; enalapril ; aldosterone secretion ; dopamine receptors ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To assess if dopaminergic control of aldosterone secretion is mediated by the renin-angiotensin system, the effect of chronic angiotensin converting enzyme inhibition by enalapril on the aldosterone response to metoclopramide has been studied in 10 patients with mild to moderate essential hypertension. Enalapril reduced supine blood pressure and increased the heart rate significantly. Plasma renin activity and urinary sodium excretion rose significantly. PRA was not changed by metoclopramide, neither during placebo nor during enalapril treatment. Metoclopramide induced a two-fold increase in plasma aldosterone, the peak response being reached within 15 min. Enalapril treatment did not alter the aldosterone response to metoclopramide. Dopaminergic control of aldosterone secretion appears to be independent of the renin-angiotensin system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547423
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  • 2
    Electronic Resource
    Electronic Resource
    The safety of adding carvedilol to hypertensive patients inadequately treated with diuretics (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. S153 
    Details
    ISSN: 1432-1041
    Keywords: carvedilol ; essential hypertension ; diuretics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single-blind, single-center study was conducted to investigate the short-term safety and efficacy of carvedilol, a new cardiovascular agent, when added to 25 mg hydrochlorothiazide (HCTZ) as combination therapy for patients inadequately treated with HCTZ alone. A total of 18 patients entered the baseline study phase, during which they received 25 mg HCTZ once daily for 4 weeks; 16 of these patients (8 men and 8 women) entered the combination treatment phase. All patients had a supine diastolic blood pressure (DBP) of ≥ 95 mm Hg prior to receiving the first dose of combination treatment. Combination treatment consisted of 25 mg HCTZ plus 12.5 mg carvedilol once daily for 2 days, followed by a forced titration of the carvedilol dose to 25 mg for 7 days. After 2 days of 12.5 mg carvedilol plus 25 mg HCTZ once daily, mean trough blood pressure was reduced as compared with baseline values. Of 16 patients, 6 (38%) achieved a trough supine DBP of 〈 90 mm Hg. After 1 additional week of combination therapy with 25 mg carvedilol, 8 of 15 patients (53%) achieved a trough supine DBP of 〈 90 mm Hg and 14 of 15 patients (93%) achieved that of 〈 95 mmHg. At each visit during the combination treatment phase, the acute reduction in blood pressure was greatest during the first 2 h after dosing. The heart rate was minimally affected by combination treatment with carvedilol at either trough levels or acutely after dosing. Nine patients experienced adverse events during combination treatment. One patient withdrew because of dizziness and fatigue. In conclusion, at an initial dose of 12.5 mg once daily, carvedilol can be safely added to HCTZ in patients whose hypertension is inadequately controlled by HCTZ alone. Results suggest that some patients may be effectively treated with 12.5 mg carvedilol added to diuretics; upward titration of carvedilol should occur after adequate evaluation of the response to this initial dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01409487
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of carvedilol on renal function (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. S96 
    Details
    ISSN: 1432-1041
    Keywords: carvedilol ; renal haemodynamics ; essential hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A randomized, double-blind, placebo-controlled study was conducted to study the effects of acute and chronic administration of carvedilol in essential hypertension, with special emphasis on renal haemodynamics and function. Acute administration of a single dose of 50 mg carvedilol reduced systolic and diastolic blood pressure without inducing reflex tachycardia. Renal blood flow was preserved; accordingly, renal vascular resistance was significantly reduced. A significant reduction in the glomerular filtration rate and filtration fraction was observed. Plasma renin activity (PRA) and plasma aldosterone values were not changed. Chronic carvedilol treatment produced a significant fall in systolic and diastolic blood pressure, heart rate, PRA and plasma aldosterone. Renal blood flow, glomerular filtration rate and filtration fraction also remained unchanged; renal vascular resistance decreased significantly. It is concluded that carvedilol possesses definite antihypertensive and renal vasodilating properties, both acutely and after chronic treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01409473
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  • 4
    Electronic Resource
    Electronic Resource
    Increase in plasma propranolol caused by nicardipine is dependent on the delivery rate of propranolol (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 121-125 
    Details
    ISSN: 1432-1041
    Keywords: Propranolol ; Nicardipine ; inhibitory effect ; delivery rate ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The influence of a single oral dose of nicardipine 30 mg on the pharmacokinetics and pharmacodynamics of propranolol 80 mg given as a conventional release formulation and as a slow release formulation was studied in two separate groups of 12 healthy volunteers. Nicardipine doubled the area under the curve (AUC) and C max of propranolol when given as a conventional formulation, but increased it only slightly when given as a slow release formulation. This pharmacokinetic interaction did not result in clinically relevant changes in pharmacodynamic responses. These results indicate that the enhancement of the bioavailability of propranolol by coadministration of nicardipine is dependent on the delivery rate of propranolol, suggesting that the interaction is mainly due to short-term haemodynamic effects of nicardipine leading to saturation of hepatic enzymes or functional shunting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00192370
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  • 5
    Electronic Resource
    Electronic Resource
    Inhibition of noradrenergic neurotransmission by apomorphine and pergolide in the in situ autoperfused rat renal and superior mesenteric vascular beds (1986)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 333 (1986), S. 229-234 
    Details
    ISSN: 1432-1912
    Keywords: Rat ; Presynaptic dopamine receptors ; Mesenteric ; Renal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In vitro studies have provided evidence that presynaptic dopamine receptors are present in the rat renal and superior mesenteric vascular beds. To confirm this in vivo, the effects of locally administered apomorphine and pergolide were studied in the in situ autoperfused renal and superior mesenteric vascular beds. Local infusion of apomorphine (1 μg · kg−1 · min−1 for 5 min) or pergolide (1 μg · kg−1 · min−1 for 5 min) into either the renal or the superior mesenteric artery had no effect on perfusion pressure per se. In the renal vascular bed, the pressure response to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) was reduced to 49.8±4.8% by apomorphine and to 54.8±2.7% by pergolide; in the mesenteric vascular bed, apomorphine reduced the pressure response to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) to 53.8±2.9, pergolide to 52.0±1.8%. Increases of perfusion pressure in the renal and in the mesenteric vascular bed induced by locally administered noradrenaline were not modified by apomorphine or pergolide. In both vascular beds, the inhibition of the stimulation-evoked pressure responses by apomorphine or pergolide was completely antagonized by local administration of the dopamine receptor antagonist haloperidol in a dose (1 μg · kg−1) which did not influence the inhibitory effect of the α2-adrenoceptor agonist UK-14,304; the α2-adrenoceptor antagonist rauwolscine, in a dose (100 μg · kg−1) which completely antagonized the inhibitory effect of UK-14,304, did not antagonize the inhibitory effects of apomorphine and pergolide. Local administration of rauwolscine per se increased the pressure response to stimulation at 4 Hz in both vascular beds. In contrast, local administration of haloperidol did not influence the stimulation-evoked pressure response. These results provide evidence for the presence of presynaptic, inhibitory dopamine receptors on sympathetic nerves in the rat renal and mesenteric vascular beds; these receptors could be involved in the blood pressure lowering effects of dopamine receptor agonists, such as apomorphine and pergolide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00512934
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  • 6
    Electronic Resource
    Electronic Resource
    Carvedilol and the kidney (1992)
    Springer
    Journal of molecular medicine 70 (1992), S. S127 
    Details
    ISSN: 1432-1440
    Keywords: Carvedilol ; Kidney ; Hypertension ; Renal hemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antihypertensive drugs have differing effects on renal hemodynamics, tubular function, plasma electrolytes, and hormonal responses. Nonselective β-blockers without intrinsic sympathomimetic activites, such as propranolol, have been reported to reduce renal blood flow and to cause a modest decrease in glomerular filtration rate. Carvedilol is a new multiple action agent displaying nonselective β-blockade without intrinsic sympathicomimetic activity, α1-adrenoceptor blockade (probably responsible for its vasodilator activity), and possibly also calcium antagonist properties. The presence of these different pharmacodynamic properties results in a different effect on the kidney as compared with, e.g., propranolol. In the dog, intrarenal infusion of carvedilol resulted in a renal vasodilator response with preservation of renal blood flow and without inducing sodium retention; in contrast, propranolol induced a renal vasoconstrictor response and sodium retention in this model. A renal vasodilator response to carvedilol was also reported in spontaneously hypertensive rats (SHR) and in DOCA-salt SHR. In contrast to labetalol, i.v. infusion of hypotensive doses of carvedilol in conscious SHR did not cause sodium retention. Carvedilol was effective in controlling hypertension and preserving renal function in a rat model of progressive hypertensive renal disease. In patients with essential hypertension, carvedilol was reported to reduce renal vascular resistance in the presence of reduced perfusion pressure, allowing for normal renal autoregulation of renal blood flow. Although a small reduction in glomerular filtration rate was seen after acute administration, renal function was preserved during chronic treatment. It is concluded from these studies that renal perfusion and renal function are well maintained during acute and chronic treatment with carvedilol. The compound does not appear to cause sodium retention, and preliminary animal test data suggest the possibility of a renoprotective effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00207623
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  • 7
    Electronic Resource
    Electronic Resource
    Population analysis of the non-linear red blood cell partitioning of draflazine following various infusion durations (1997)
    Springer
    European journal of clinical pharmacology 53 (1997), S. 57-63 
    Details
    ISSN: 1432-1041
    Keywords: Key wordsDraflazine ; Population analysis; nucleoside transport inhibitor ; non-linear red blood cell partition ing ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics and non-linear red blood cell partitioning of the nucleoside transport inhibitor draflazine were investigated in 19 healthy male and female subjects (age range 22–55 years) after a 15-min i.v. infusion of 1 mg, immediately followed by infusions of variable rates (0.25, 0.5 and 1 mg · h−1) and variable duration (2–24 h). Methods: The parameters describing the capacity-limited specific binding of draflazine to the nucleoside transporters located on erythrocytes were determined by NONMEM analysis. The red blood cell nucleoside transporter occupancy of draflazine (RBC occupancy) was evaluated as a pharmacodynamic endpoint. Results: The population typical value for the dissociation constant K d (%CV) was 0.648 (12) ng · ml−1 plasma, expressing the very high affinity of draflazine for the erythrocytes. The typical value of the specific maximal binding capacity Bmax (%CV) was 155 (2) ng · ml−1 RBC. The interindividual variability (%CV) was moderate for K d (38.9%) and low for Bmax (7.8%). As a consequence, the variability in RBC occupancy of draflazine was relatively low, allowing the justification of only one infusion scheme for all subjects. The specific binding of draflazine to the red blood cells was a source of non-linearity in draflazine pharmacokinetics. Steady-state plasma concentrations of draflazine virtually increased dose-proportionally and steady state was reached at about 18 h after the start of the continuous infusion. The t1/2βaveraged 11.0–30.5 h and the mean CL from the plasma was 327 to 465 ml · min−1. The disposition of draflazine in whole blood was different from that in plasma. The mean t1/2β was 30.2 to 42.2 h and the blood CL averaged 17.4–35.6 ml · min−1. Conclusion: Although the pharmacokinetics of draflazine were non-linear, the data of the present study demonstrate that draflazine might be administered as a continuous infusion over a longer time period (e.g., 24 h). During a 15-min i.v. infusion of 1 mg, followed by an infusion of 1 mg · h−1, the RBC occupancy of draflazine was 96% or more. As the favored RBC occupancy should be almost complete, this dose regimen could be justified in patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050337
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  • 8
    Electronic Resource
    Electronic Resource
    Inhibitory effects of apomorphine and pergolide on neurogenic vasoconstriction in the hindquarters of the rat (1985)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 329 (1985), S. 146-151 
    Details
    ISSN: 1432-1912
    Keywords: Apomorphine ; Pergolide ; Autoperfused rat hindquarters ; Dopamine receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of locally administered apomorphine and pergolide were studied in the isolated autoperfused hindquarters of the rat, in an attempt to assess the possible role of presynaptic dopamine receptors at the level in the hypotensive effect of these dopamine agonists. Local infusion of apomorphine (1μg·kg−1·min−1 for 5 min) or pergolide (1μg·kg−1·min−1 for 5 min) [into the hindquarters] did not alter perfusion pressure per se, but reduced the pressor response to electrical stimulation of the lumbar sympathetic chains for the whole frequency range used during a cumulative frequency-response curve (0.25–16 Hz, 1 ms, supramaximal voltage). Apomorphine and pergolide reduced the pressor response elicited by 4 Hz electrical stimulation (applied until maximum response was reached) to 54.8±7.1% and 53.9±1.7% respectively, but they did not modify similar increases of perfusion pressure produced by locally administered noradrenaline. The inhibition by apomorphine and pergolide of the 4 Hz stimulation-evoked pressor response was completely antagonized by local administration of the dopamine antagonist haloperidol (1μg·kg−1), but was not influenced by the α2-antagonist rauwolscine (100μg·kg−1). This dose of rauwolscine antagonized the inhibitory effect of the α2-agonist UK-14,304, which was not influenced by haloperidol. Local administration of rauwolscine increased the pressor response to stimulation at 4 Hz by 37.4–46.2%. In contrast, local administration of haloperidol did not influence the 4 Hz stimulation-evoked pressor response. These results indicate that dopamine receptors are pressent on the sympathetic innervation of the vascular bed in the rat hindquarters but do not provide evidence for a physiological role of these receptors in modulating peripheral sympathetic neurotransmission. Stimulation of these receptors, leading to a decrease of noradrenaline release and thus of vasomotor tone, might—at least in part—explain the blood pressure lowering effects of intravenous apomorphine and pergolide in the rat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501204
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