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  • 1
    ISSN: 1432-1041
    Keywords: dihydroergotamine ; acute and chronic effects ; venous function ; plasma levels ; dose-response relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, interindividual comparative study 30 healthy volunteers were randomly allocated to oral treatment with 5 or 10 mg of dihydroergotamine (DHE) or placebo once daily for 16 days. Regional basic venous blood volume (BBV), pressure dependent venous capacitance (Cv) of the calf, resting heart rate and blood pressure were determined on Days 1 and 15 of treatment. Plasma concentrations of DHE were monitored on Days 2 and 16. Due to spontaneous vasodilation BBV varied considerably, showing that it is an inappropriate parameter for investigating the venoconstrictor activity of DHE. Cv remained unchanged after the first dose of DHE but it had declined significantly on both dosage regimens at the end of the treatment phase. In contrast, the blood concentration profiles of DHE were comparable at the beginning and the end of the trial. The discrepancy can best be explained by the existence of an effect compartment, e.g. smooth vascular musculature, which slowly becomes filled with DHE and/or its active metabolites. The venoconstrictor activity of DHE exhibited a significant dose-response relationship.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 435-439 
    ISSN: 1432-1041
    Keywords: co-dergocrine mesylate ; hypertension ; aldosterone ; catecholamines ; nifedipine ; renin side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Co-dergocrine mesylate (Cod), which inhibits norepinephrine secretion by stimulating presynaptic dopamine receptors, and has no known metabolic side effect, has an additive antihypertensive effect to that of Nifedipine (Nif). Plasma norepinephrine, epinephrine, renin activity and aldosterone have been measured after acute administration of Nif and Cod alone and in combination to 18 patients with a diastolic blood pressure 〉 105 mm Hg in a cross-over, randomized, double-blind study. Every patient received 4 mg Cod then 20 mg Nif, placebo then 20 mg Nif and 4 mg Cod then placebo. The second treatment was always given 1 h after the first medication. Blood pressure was measured before and every 15 min during the study period. Blood for measurement of catecholamines, aldosterone and renin activity was collected before medication, 1 h after the first dose and 90 min after the second treatment. Blood pressure was significantly lower (P 〈 0.05) where Cod preceded Nif. Cod caused a significant decrease in plasma norepinephrine from 293 to 202 pg · ml−1 and in epinephrine from 67 to 55 pg · ml−1. The Nif-induced increase in norepinephrine from a pre-treatment value of 293 pg · ml−1 with preceding Cod to 331 pg · ml−1 was much less than the increase with placebo as premedication, from 284 to 440 pg · ml−1. Nif caused an increase in renin activity but no increase in aldosterone. Nif-related side effects, such as flushing and headache, occurred in 6 patients of whom 5 had no received Cod as premedication. Due to the stabilizing action of Cod on catecholamines and on the side effects of Nif, Cod may be preferable to other antihypertensives in augmenting the antihypertensive action of Nif.
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  • 3
    ISSN: 1432-1041
    Keywords: myocardial oxygen consumption ; beta-adrenoceptor blockade ; atenolol ; pindolol ; adrenaline ; free fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of adrenaline on myocardial oxygen consumption (MVO2) during selective and non-selective beta-adrenoceptor blockade was examined in 26 patients with angina pectoris. Cardiac venous flow was measured by thermodilution and blood was sampled for metabolic studies. Thirteen patients were given atenolol 62.5 µg/kg i.v. and the other 13 patients pindolol 7.5 µg/kg i.v. Measurements were repeated before and during infusion of adrenaline 0.1 µg/kg/min. Compared to the control situation, adrenaline increased MVO2 more in atenolol-treated (39%) than in pindolol-treated patients (11%). This was partly due to augmented external cardiac work. Arterial FFA was considerably increased in the atenolol group (105%), but was unchanged in the pindolol group, suggesting an additional metabolic mechanism. Thus, adrenaline stimulation, which is comparable to that found in acute myocardial infarction, increases MVO2 more during selective than non-selective beta-blockade.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 529-534 
    ISSN: 1432-1041
    Keywords: beta-adrenoceptor blocking agents ; hypertension ; adverse reactions ; atenolol ; bopindolol ; pindolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy of once-daily bopindolol, a nonselectiveβ-adrenoceptor blocking agent with partial agonist activity, and of pindolol and atenolol in the treatment of essential hypertension has been compared. 369 patients were investigated in a double-blind parallel-group study. The treatment period was 10 weeks. Blood pressure normalisation (diastolic BP equal to or less than 90 mmHg) was to be achieved by a stepwise increase in the dose of the test drugs, and, if required, by addition of a diuretic. Normalisation of blood pressure was achieved in 71 to 76% of the subjects, with no significant differences between bopindolol, pindolol, and atenolol. Special attention was given to evaluation of side effects by using two methods for registration of all adverse events during the study. A low incidence of drug-induced side effects was observed, with no significant difference between bopindolol, pindolol, and atenolol. There was no evidence of unsuspected adverse reactions due to bopindolol.
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  • 5
    ISSN: 1432-1041
    Keywords: myocardial oxygen consumption ; beta-adrenoceptor blockade ; atenolol ; pindolol ; adrenaline ; free fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of adrenaline on myocardial oxygen consumption (MVO2) during selective and non-selective beta-adrenoceptor blockade was examined in 26 patients with angina pectoris. Cardiac venous flow was measured by thermodilution and blood was sampled for metabolic studies. Thirteen patients were given atenolol 62.5 µg/kg i.v. and the other 13 patients pindolol 7.5 µg/kg i.v. Measurements were repeated before and during infusion of adrenaline 0.1 µg/kg/min. Compared to the control situation, adrenaline increased MVO2 more in atenolol-treated (39%) than in pindolol-treated patients (11%). This was partly due to augmented external cardiac work. Arterial FFA was considerably increased in the atenolol group (105%), but was unchanged in the pindolol group, suggesting an additional metabolic mechanism. Thus, adrenaline stimulation, which is comparable to that found in acute myocardial infarction, increases MVO2 more during selective than non-selective beta-blockade.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 35 (1988), S. 53-57 
    ISSN: 1432-1041
    Keywords: codergocrine ; prolactin ; hydergine ; pharmacokinetics ; systemic availability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the absolute systemic availability (f) of an oral formulation (Hydergin spezial = Hydergine FASR 4 mg per tablet) of codergocrine by three different methods. Twelve healthy volunteers received single doses of 0.9 mg co-dergocrine intravenously and 8.0 mg orally in a randomized crossover design. The pharmacological effect of co-dergocrine was monitored as a reduction in plasma prolactin. Maximal plasma concentrations of co-dergocrine after oral dosing ranged between 0.181 and 1.307 ng·ml−1. Maximal urinary excretion ranged between 4.7 and 9.9 µg·h−1 and between 0.3 and 2.3 µg·h−1 after intravenous and oral doses respectively. Clearance was measured as 90±22 l·h−1 and the absolute systemic availability (f) as 2.25±0.65% by using the areas under the plasma concentration-time curves extrapolated to infinity. Calculation of f by comparing areas up to 32 h or the fractions of the dose excreted in urine led to identical results. The intravenous and oral doses produced similar pharmacological effects (reduction of plasma prolactin concentrations) despite the small value of f.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 35-39 
    ISSN: 1432-1041
    Keywords: salmon calcitonin ; osteoporosis ; corticoid-induced osteoporosis ; chronic obstructive lung disease ; bone mineral content ; 125iodine photon absorptiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary There is uncertainty about the best treatment for steroid-induced osteoporosis. Thirty-six patients with steroid-dependent, chronic obstructive lung disease and associated steroid osteoporosis have been studied, of whom 18 were treated with salmon calcitonin and the other 18 served as controls. Treatment lasted for 6 months and consisted of 100 I.U. s.c. every other day. In the controls there were significant decrements of 1.4% and 3.5%, respectively, in cortical and cortical and trabecular bone mineral content, whereas in subjects on calcitonin there were increments of 2.6% and 2.7%, respectively. Additional evidence of positive effect of calcitonin was derived from the reduced incidence of new fractures occurring during the observation period. A significant reduction in back pain was a further consequence of the hormone therapy.
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  • 8
    ISSN: 1432-1041
    Keywords: Parkinson's disease ; Bromocriptine ; L-Dopa/benserazide ; early combination therapy ; long-term ; therapy ; mortality ; cardioprotection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary L-Dopa supplemented by a peripheral decarboxylase inhibitor is considered the most potent therapeutic regimen prolonging active life in Parkinsonian patients. The long-term benefit of therapy is limited by adverse effects, such as dyskinesia and on-off phenomena, which can be mitigated by the concomitant administration of dopamine agonists, such as bromocriptine. In order to quantify the beneficial impact of early combination therapy, a controlled clinical trial (PRADO:PRA vi-del1 +DOpa) in patients with early Parkinson's disease was carried out, whereby L-Dopa monotherapy (in a fixed combination with benserazide (DoBe) was being compared with the same combination plus bromocriptine (DoBeBro). Patients were recruited and treated by 101 practising neurologists in the Federal Republic of Germany and in Hungary. 'Twenty seven clinical university centers cross-checked the patients at regular intervals. The trial started with 3 months of DoBe monotherapy (median dose of 375 mg L-Dopa for both randomized groups) followed by gradual substitution of DoBe by bromocriptine over 3 months in one of the groups (250 mg L-Dopa/10 mg bromocriptine). The target medication was maintained from study months 6 to 54. Parkinsonian symptoms were classified according to the Webster rating scale, the Hoehn and Yahr scale and the Zung Self-Rating Depression Scale. Adverse events and life status were checked at regular intervals. Special emphasis was given to motor performance tests. 587 patients (302 in the DoBe group and 285 in the DoBeBro group) were available for intention-to-treat analysis. Both groups were homogeneous at baseline in all observed parameters. DoBe and DoBeBro proved equi-effective in terms of antiparkinsonian activity after the substitution phase (P II) had been completed. In September 1991, after a median observation period on target medication of 38.4 months in the DoBe group and 40.1 months in the DoBeBro group, 18 versus 8 deaths had been registered. The Logrank test as well as analysis using the Cox model, both adjusted for age and sex, showedP-values of 0.018 and 0.021, respectively. The mortality risk associated with L-Dopa therapy was reduced by more than 50 % by its combination with bromocriptine. The study was terminated due to this difference in mortality. The causes of death were classified by the treating physicians and consultants. At the time of study termination 152 patients in the DoBe group and 121 in the DoBeBro group had already discontinued study medication. Of those further 26 patients had died by the date of the final evaluation, 15 on DoBe and 11 on DoBeBro. The results imply that combination therapy with bromocriptine should be preferred over L-Dopa monotherapy from the very beginning.
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  • 9
    ISSN: 1432-1041
    Keywords: beta-blocker ; atenolol ; pindolol ; plasma free fatty acids ; growth hormone ; blood glucose ; myocardial oxygen consumption ; myocardial efficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 12 normal volunteers the interaction between the metabolic and cardiovascular effects of adrenaline and either a cardioselective (atenolol 150 mg p. o. for 1 week) or a non-selectiveβ-blocker with intrinsic sympathomimetic activity (pindolol 15 mg p. o. for 1 week) were studied. Equiactive doses of theβ-blockers were investigated with respect to their metabolic effects. There were profound differences in the metabolic profile of the two substances: the non-cardioselective beta-blocker caused significant inhibition of the lipolytic, glycogenolytic and the growth hormone-releasing effects of adrenaline when compared to the cardioselective agent. The results indicate that, during non-cardioselective beta-blockade, metabolic effects occur which should favourably influence myocardial oxygen consumption by making myocardial performance more economical.
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  • 10
    Publication Date: 1988-01-01
    Print ISSN: 0031-6970
    Electronic ISSN: 1432-1041
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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