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排序方式: 共有282条查询结果,搜索用时 15 毫秒
1.
2.
F. V. Costa C. Borghi A. Mussi E. Ambrosioni 《European journal of clinical pharmacology》1986,30(2):145-150
Summary The long-term efficacy of a new vasodilator, cadralazine (ISF 2469), and chlorthalidone have been compared in 20 hypertensive patients not adequately controlled by atenolol. After 4 weeks of treatment with atenolol 100 mg once daily, patients whose diastolic blood pressure was >95 mmHg were randomly divided into two groups to receive in addition to atenolol, either cadralazine 15 mg once daily or chlorthalidone 25 mg once daily. Both treatments were administered for 6 months. At the end of treatment with atenolol and after 3 and 6 months of combination therapy, blood pressure and heart rate were measured at rest and during bicycle exercise 24 h after the last dose. Compared to atenolol alone, both cadralazine and chlorthalidone caused a significant and similar reduction in resting blood pressure. Both groups showed an increase in diastolic blood pressure during exercise while receiving atenolol alone. The addition of chlorthalidone did not modify the pressor response to exercise, whereas patients taking cadralazine had a decrease in exercise diastolic blood pressure, which was fully evident after 6 months of therapy. The reduction in exercise diastolic blood pressure induced by cadralazine was proportional to the increase in exercise heart rate, suggesting a fall in peripheral vascular resistance. Chlorthalidone caused a significant increase in serum glucose and uric acid and a decrease in K+, whereas no change was observed during cadralazine It is concluded that cadralazine given once a day with atenolol has the same efficacy in controlling blood pressure at rest as the combination of atenolol and chlorthalidone, and in addition it improves the pressor response to dynamic exercise and does not cause unwanted metabolic effects. 相似文献
3.
Herbert Thurston 《Clinical and experimental pharmacology & physiology》1992,19(S19):67-71
1. Perindopril (4 mg) was compared with atenolol (50 mg), captopril (25 mg b. d.) or a diuretic (hydrochlorothiazide 50 mg and amiloride 5 mg) in three studies involving a total of 503 hypertensive patients with a diastolic blood pressure (DBP) of 95–125 mmHg.
2. A 4 week single-blind placebo period preceded 12 weeks of active treatment. Dose titration was at weeks 4 and 8 if supine DBP >90 mmHg. The dose was doubled and if necessary a diuretic was added in the atenolol or captopril comparisons, and atenolol was added in the diuretic study.
3. The fall in supine blood pressure (BP) was 27/17 mmHg with perindopril and 21/16 mmHg for atenolol. Monotherapy controlled 55% of patients on perindopril and 48% on atenolol, increasing to 78% and 58% with the addition of hydrochlorothiazide, respectively. Captopril caused a BP fall of 19/12 mmHg compared with 27/18 mmHg for perindopril, with 49% of both groups being controlled on monotherapy.
4. Diuretic addition produced a greater antihypertensive effect with perindopril (75%) compared with 57% for captopril in achieving control. Perindopril caused a comparable fall in supine BP to the diuretic combination 27/19 mmHg and 31/18 mmHg, but the fall in erect systolic BP was significantly greater for the diuretic. At 3 months, 85% of the diuretic group and 78% of the perindopril group achieved the target BP.
5. A multicentre trial of 856 patients treated with perindopril (690 patients treated for 1 year or more) has shown that BP control is maintained in the long term with a low incidence of side-effects (7.9%) causing withdrawal from treatment. These studies demonstrate that perindopril compares favourably with standard first-line therapy for mild to moderate hypertension. 相似文献
2. A 4 week single-blind placebo period preceded 12 weeks of active treatment. Dose titration was at weeks 4 and 8 if supine DBP >90 mmHg. The dose was doubled and if necessary a diuretic was added in the atenolol or captopril comparisons, and atenolol was added in the diuretic study.
3. The fall in supine blood pressure (BP) was 27/17 mmHg with perindopril and 21/16 mmHg for atenolol. Monotherapy controlled 55% of patients on perindopril and 48% on atenolol, increasing to 78% and 58% with the addition of hydrochlorothiazide, respectively. Captopril caused a BP fall of 19/12 mmHg compared with 27/18 mmHg for perindopril, with 49% of both groups being controlled on monotherapy.
4. Diuretic addition produced a greater antihypertensive effect with perindopril (75%) compared with 57% for captopril in achieving control. Perindopril caused a comparable fall in supine BP to the diuretic combination 27/19 mmHg and 31/18 mmHg, but the fall in erect systolic BP was significantly greater for the diuretic. At 3 months, 85% of the diuretic group and 78% of the perindopril group achieved the target BP.
5. A multicentre trial of 856 patients treated with perindopril (690 patients treated for 1 year or more) has shown that BP control is maintained in the long term with a low incidence of side-effects (7.9%) causing withdrawal from treatment. These studies demonstrate that perindopril compares favourably with standard first-line therapy for mild to moderate hypertension. 相似文献
4.
Joost B. M. M. van Bree Anne V. Baljet Anton van Geyt Albertus G. de Boer Meindert Danhof Douwe D. Breimer 《Journal of pharmacokinetics and pharmacodynamics》1989,17(4):441-462
The unit impulse response theory has been adapted to characterize the transport profile of drugs into the central nervous system (CNS). From the obtained input function, the cumulative plasma volume (V) cleared by transport into the CNS in time can be calculated. Simulation studies demonstrated that transport governed by passive diffusion resulted in a linear relationship between V and time, while the slope of the line, the blood- brain barrier (BBB) clearance, proved to be an adequate and model independent parameter to characterize drug transport into the CNS. The error in the result of the numerical procedure could be limited to less than 10% of the theoretically predicted value. Superposition of 5 or 10% random noise on simulated data did not result in significant differences between the calculated and theoretically predicted clearance values. Simulations of carrier-mediated transport resulted in nonlinear transport curves; the degree of nonlinearity, and thus the detectability, was dependent on the initial degree of saturation of the system, the rate of desaturation, as caused by drug elimination processes and the noise level on the data. In vivoexperiments in the rat were performed, using atenolol, acetaminophen, and antipyrine as model drugs. Linear transport relationships were obtained for all drugs, indicating that transport was dependent on passive diffusion or a low affinity carrier system. BBB- clearance values were 7±1 l/min for atenolol, 63±7 ul/min for acetaminiphen and 316±25 l/min for antipyrine. These experiments validate the applicability of the presented technique in in vivostudies. 相似文献
5.
E. van der Veur B. S. ten Berge A. J. M. Donker J. F. May F. H. Schuurman H. Wesseling 《European journal of clinical pharmacology》1985,28(5):507-511
Summary After screening two local populations in the northern part of The Netherlands for hypertension, patients with a diastolic pressure (DP) between 95 and 120 mmHg were treated daily either with 50 mg hydrochlorothiazide or 100 mg atenolol. Non-responders were given the combination and if necessary the dose of atenolol was increased to 200 mg. Non-responders to the latter combination were randomized and treated either with 50 mg hydrochlorothiazide and labetalol or with 50 mg hydrochlorothiazide, 200 mg atenolol and prazosin. If after 1 month a DP90 mmHg had been reached the patient was reassessed after a further 3 months. If a DP>90 mmHg was found the dose of labetalol or prazosin was increased and the patient was re-examined after 1 month.This protocol was followed until the maximum dose was reached or adverse reactions prevented a further increase in dosage.During 6 months of treatment there was a further drop in systolic and diastolic blood pressures under both regimens of, respectively, 8.6 and 2.4 mmHg for labetalol, and 7.7 and 5.0 mmHg for the prazosin group. At the end of the period the average daily doses of labetalol and prazosin were 1256 mg and 4.3 mg, respectively. There was no significant difference in the average number of complaints between the labetalol and the prazosin group. 相似文献
6.
Summary A randomized, placebo-controlled, double-blind crossover investigation in 12 patients with non-asthmatic chronic obstructive lung disease and co-existing stable angina pectoris was done to compare two 1-selective adrenoceptor blocking agents, atenolol 100 mg and bisoprolol 20 mg. Systolic and diastolic blood pressures (SBP, DBP), heart rate (HR) as well as airway resistance (AWR, and less frequently forced expiratory volume in 1 s (FEV1) and intrathoracic gas volume (ITGV) were measured in the sitting position before and at various times up to 24 h after drug intake.During the first 4 h both beta-blockers produced a significant reduction in HR in comparison to placebo (p<0.01). Atenolol 100 mg significantly increased AWR relative to placebo and bisoprolol (p<0.05). After 24 h, a significant reduction in HR (p<0.01) could only be demonstrated after bisoprolol, whereas atenolol alone led to a significant elevation in AWR relative to placebo and bisoprolol (p<0.05) at that time.It is concluded that bisoprolol appears to have a high degree of beta1-selectivity, thus providing a wide split between beta1- and beta2-adrenoceptor blockade. Bisoprolol in its therapeutic dose range is expected to be relatively safe as regards bronchoconstriction in patients suffering both from hypertension and/or angina pectoris and chronic obstructive lung disease. 相似文献
7.
8.
R. van der Does L. Widmann H. -J. überbacher M. H?rrmann M. Machwirth U. Stienen 《European journal of clinical pharmacology》1990,38(Z2):S147-S152
Carvedilol [25 mg once daily] (o. d.) was compared to atenolol (50 mg o. d.) as an adjunct to pre-existing hydrochlorothiazide (HCTZ) monotherapy in patients with mild to moderate hypertension [diastolic blood pressure (DBP),100–115 mm Hg]. After a placebo run-in phase of 2 weeks, 131 patients received 25 mg HCTZ o. d. for 4 weeks. In all, 122 patients were transferred to the double-blind phase, in which 25 mg carvedilol or 50 mg atenolol was randomly added to HCTZ. After an additional 6 weeks of treatment, 112 patients were evaluable for efficacy (C/HCTZ group,n = 54; A/HCTZ group,n = 58). Blood pressure was measured and the heart rate was counted before medication, at 2-week intervals throughout the trial, and 2 h after medication on the 1st and the last day of the combination treatment period. Serum lipids were measured in addition to routine laboratory variables. A therapeutic response was defined as a reduction in supine and standing diastolic blood pressure to values of < 90=" mmhg.=" in=" a=" relatively=" low=" number=" of=" patients=" (6=" of=" 131),=" a=" response=" as=" defined=" above=" was=" achieved=" with=" hctz=" alone.=" this=" may=" be=" accounted=" for=" by=" the=" fact=" that=" patients=" were=" required=" to=" have=" a=" diastolic=" blood=" pressure=" of=" at=" least=" 100=" mghg=" and=" by=" the=" relatively=" short=" period=" of=" monotherapy.=" the=" two=" groups=" of=" patients=" receiving=" different=" combination=" treatments=" were=" well=" matched=" for=" demographic=" data=" and=" blood=" pressure=" values=" before=" the=" adjunct=" was=" added.=" in=" both=" groups=" there=" was=" a=" marked=" additional=" blood=" pressure=" decrease=" on=" the=" initiation=" of=" combined=" treatment.=" at=" the=" end=" of=" the=" study=" the=" medians=" of=" all=" blood=" pressure=" values=" were=" well=" within=" normal=" ranges,=" which=" was=" not=" the=" case=" with=" hctz=" alone.=" on=" the=" last=" day=" of=" the=" trial,=" the=" responders=" comprised=" 67%=" of=" the=" c/hctz=" group=" and=" 71%=" of=" the=" a/hctz=" group.=" no=" relevant=" changes=" in=" lipid=" values=" were=" observed=" with=" combination=" treatment=" vs=" diuretic=" monotherapy.=" no=" serious=" adverse=" event=" attributable=" to=" one=" of=" the=" study=" drugs=" was=" reported.=" the=" results=" of=" the=" present=" trial=" suggest=" that=" the=" antihypertensive=" efficacy=" of=" both=" combinations=" is=" superior=" to=" that=" of=" hctz=" alone=" and=" that=" there=" is=" no=" difference=" in=" efficacy=" between=" the=" two=" combinations.=" adding=" carvedilol=" or=" atenolol=" to=" pre-existing=" hctz=" appears=" to=" be=" safe.=" the=" tolerability=" of=" the=" antihypertensive=" treatment=" does=" not=" seem=" to=" decline,=" despite=" considerable=" additional=" decreases=" in=" blood="> 相似文献
9.
The Use of Intracerebral Microdialysis to Determine Changes in Blood-Brain Barrier Transport Characteristics 总被引:2,自引:0,他引:2
de Lange Elizabeth C. M. Hesselink Mayke B. Danhof Meindert de Boer Albertus G. Breimer Douwe D. 《Pharmaceutical research》1995,12(1):129-133
The aim of this study was to determine whether changes in the transport of drugs into the brain could be determined by in vivo intracerebral microdialysis. Atenolol was used as a model drug to determine blood-brain barrier (BBB) transport characteristics. In rats, unilateral opening of the blood-brain barrier was achieved by infusion of hyperosmolar mannitol (25%, w/v) into the left internal carotid artery. BBB transport, expressed as the ratio of the area under the curve (AUC) of atenolol in brain extracellular fluid over plasma, was three times higher for the mannitol treated hemisphere as compared with the contralateral brain or after infusion of saline, being (mean ± SEM) 0.094 ± 0.024 (n = 16), 0.029 ± 0.007 (n = 12) and 0.030 ± 0.009 (n = 12) respectively. Further evaluation of the data indicated that for experiments performed in the morning the mannitol infusion had little effect on the extent of transport of atenolol into the brain, while in the afternoon BBB transport was about 10-fold higher than in the contralateral and saline group. The mean afternoon ratios ± SEM were 0.155 ± 0.038 (n = 8), 0.012 ± 0.003 (n = 6) and 0.018 ± 0.006 (n = 6) respectively. It is concluded that intracerebral microdialysis is capable of revealing changes in BBB transport and regional and time-dependent differences in drug levels can be demonstrated with the use of this technique. 相似文献
10.
F. M. Belpaire M. G. Bogaert M. Rosseneu 《European journal of clinical pharmacology》1982,22(3):253-256
Summary The binding of 8 -adrenergic blocking drugs to human serum albumin, to 1-acid glycoprotein and to serum from normal volunteers and from patients with rheumatoid arthritis was studied. Protein binding was determined in vitro using equilibrium dialysis of labelled drug at 25° C. Oxprenolol and propranolol were highly bound to serum, alprenolol, pindolol and timolol to a lesser degree, and atenolol, metoprolol and sotalol were negligibly bound. For the five compounds which were appreciably bound, the mean binding was significantly higher in serum from patients with rheumatoid arthritis than in serum from normal volunteers. For those drugs, binding to 1-acid glycoprotein was higher than to human serum albumin, and binding to a mixture of both proteins approached that to serum from healthy volunteers. For each of these drugs there was a strong correlation between the serum 1-glycoprotein concentration and the percentage binding. 相似文献