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1.
目的探讨阻塞性睡眠呼吸暂停综合征(OSAS)患者心脏自主神经调节功能改变与心律失常的关系。方法 118例主诉打鼾患者经多导睡眠呼吸监测仪(PSG)行整夜睡眠监测,并同步监测24-h动态心电图。根据呼吸暂停低通气指数(AHI)将118例患者分为重度OSAS组(A组,46例,AHI>40)、轻中度OSAS组(B组,45例,5≤AHI≤40)和单纯鼾症组(C组,27例,AHI<5)。结果 A组时域指标SDNN、SDANN指数均显著低于B组和C组,心率变异性频域指标LF显著高于B组和C组(P<0.05)。相关分析显示,氧减指数(ODI)、血氧低于90%的时间比(T90)、最低血氧饱和度(LSaO2)与SDNN、SDANN指数和LF显著相关(P<0.05)。A组心律失常发生率为71.7%,明显高于B组的48.9%和C组的29.6%(P<0.05)。结论 OSAS患者心率变异性变化与间歇低氧血症相关,心脏自主神经调节功能改变可能是OSAS导致心律失常的重要机制之一。  相似文献   

2.
The effects of a phenothiazine, promethazine, on sleep in ten healthy volunteers were investigated in two double blind polygraphic studies. The first part consisted of a single dose study with promethazine 50, 100, and 200 mg, using pentobarbital 100 mg as a reference substance. In the second part, four subjects spent 20 consecutive nights with nine drug nights (promethazine 100 mg), followed by a placebo withdrawal period of six nights, in the sleep laboratory.Promethazine showed a dose related REM-depressing effect with a greater decrease, the higher the dose. The placebo value was 20.7% REM of total sleep time and gave 16.3, 13.5 and 11.4 respectively, for promethazine 50, 100 and 200 mg. Pentobarbital gave 16.2% REM. There was also an increase of stage II and with the highest dose an increase of stage III + IV. An increase of REM-latency together with a decrease of REM-periods was also seen, and while pentobarbital gave a decrease in REM-density, promethazine did not cause any changes in the phasic REM-component. A REM-rebound was seen in the first night of withdrawal with an increase of per cent REM from 19.9–25.1%. The mean for the whole withdrawal period was 23.1%. Promethazine in the highest dose, 200 mg, gave drowsiness and hangover effects in 14 nights out of 20. The REM-depressing effect of promethazine together with its relatively weak REM-rebound effect may explain its value in the treatment of withdrawal symptoms following abuse of alcohol and barbiturates.  相似文献   

3.
陈敏  蒋雯 《中国医院药学杂志》2016,36(22):2004-2007
目的:观察螺内酯对慢性心力衰竭(CHF)患者心脏自主神经功能的影响。方法:回顾性收集某院2012年12月-2014年12月收治的CHF患者52例,按照给药方案的不同分为观察组和对照组。对照组26例采取基础抗心衰方案治疗;观察组26例在基础抗心衰治疗上加用螺内酯(20 mg·d-1),治疗前1天及治疗后16周行动态超声心动图检查,通过系统分析得出心率变异性(HRV)的时域及频域分析指标。结果:与对照组比较,螺内酯治疗16周后HRV明显改善(t=13.406,P<0.05);时域指标:全部窦性R-R间期的标准差(SDNN)、全部窦性R-R间期差值的均方根(rMSSD)、每5分钟窦性R-R平均值的标准差(SDANN)、SDNN的均值(SDNNI)均明显升高(t=5.829,10.256,6.005,7.128,P<0.05);频域指标:低频(LF)、高频(HF)也明显提高(t=9.231,7.441,P<0.05)。结论:螺内酯可明显改善CHF患者的HRV,改善心脏自主神经功能。  相似文献   

4.
The chiral compound reboxetine is used as a selective noradrenaline reuptake inhibitor (NARI) for the treatment of major depressive disorders. The pharmacokinetic variability of the enantiomers of the drug (S,S- and R,R-reboxetine) was studied using stereoselective high-performance liquid chromatography with mass spectrometric detection in a controlled clinical monotherapy situation (trial I) and a naturalistic clinical setting (trial II). Trial I included patients receiving racemic reboxetine as 6-month monotherapy for treatment of major depressive disorder. Trough level serum samples in steady state were analyzed for the concentration of the reboxetine enantiomers in study weeks 4, 12, and 24. In a therapeutic drug monitoring setting (trial II), 47 patients on doses ranging from 4 to 16 mg daily, including much polypharmacy, trough level steady-state serum samples were analyzed by the same bioanalytical method. Data from trials I and II were assessed to determine the inter- and intraindividual pharmacokinetic outcomes. The results showed that the median S,S/R,R ratio in steady state was 0.5 and ranged from 0.22 to 0.88. It was also shown that women have an approximately 30% higher S,S/R,R ratio than men. The S,S/R,R ratios of reboxetine were not found to correlate with reboxetine concentrations. To investigate the NARI activity of a circulating serum reboxetine concentration, a recalculation of the determined enantiomeric concentrations to previously demonstrated experimental NARI potencies of the drug enantiomers was performed. This partly novel concept of estimating pharmacodynamic activity showed that the serum NARI activity in women tended to be higher than in men at a given reboxetine concentration. In conclusion, the variability in the NARI activity per nmol/L reboxetine and the variability in the concentration outcome of the reboxetine enantiomers may justify the use of enantioselective drug monitoring in the clinic. The gender aspects of the drug have to be further assessed.  相似文献   

5.
RATIONALE: Though reboxetine, a selective noradrenaline reuptake inhibitor, causes autonomic and cognitive adverse events there is a paucity of appropriately designed studies on the cognitive and autonomic effects of the drug in the literature. OBJECTIVE: To compare the effects of reboxetine on cognitive and autonomic functions with those of placebo in healthy humans. METHOD: A randomised, double-blind, crossover study of 12 healthy male volunteers aged 25 (21-27; median, range) years. Subjects orally received 4 mg reboxetine and placebo twice daily for periods of 14 days each with at least 14 days in between. Vasoconstrictory response of cutaneous vessels (VR) and skin conductance response (SCR) following sudden deep breath were employed as parameters for autonomic function. Quantitative EEG (qEEG) and psychometric tests served as parameters for cognitive function. RESULTS: Reboxetine decreased SCR and prolonged the dilation phase of VR (P<0.05). It did not affect cognitive functions such as flicker fusion frequency, choice reaction, memory and psychomotor coordination but increased slow beta (beta1) power density in the qEEG. Tiredness (n=12), dry mouth (n=9), delayed urination (n=3) and constipation (n=1) were noted with reboxetine. CONCLUSION: Sustained peripheral and/or central sympathetic activation accounts for the prolongation of VR. The decrease of SCR and typical side effects suggest a relevant antimuscarinic drug action. Chronic administration of reboxetine at therapeutic doses causes autonomic dysfunction and subjective sedation but does not impair cognitive and psychomotor abilities in healthy humans.  相似文献   

6.
The effects of benidipine hydrochloride (CAS 91559-74-5, Coniel) on autonomic nervous activity in hypertensive patients with high- and low-salt diets were investigated. Six patients having a urinary sodium excretion of 80 mEq/day or less (low salt group) and 6 patients having a urinary sodium excretion of 200 mEq/day or more (high salt group) were orally given benidipine hydrochloride (4 mg). Before and four weeks after the treatment with benidipine, 24-h circadian variation in blood pressure and 24-h Holter electrocardiogram (ECG) were recorded. The low frequency power spectrum of heart rate (LF power; 0.04-0.15 Hz), high frequency power spectrum of heart rate (HF power; 0.15-0.40 Hz), and the ratio of LF to HF (LF/HF) were calculated, and these parameters were averaged every hour in every subject. HF power was significantly lower and LF/HF ratio was significantly higher in the high-salt group than in the low-salt group before the treatment. However, the benidipine treatment significantly increased the HF power in both groups, particularly in the high-salt group, and significantly decreased the LF/HF ratio in both groups. Moreover, there was no significant difference in the antihypertensive effect of benidipine between the high- and low-salt intake groups. These results suggest that benidipine favourably influences blood pressure and autonomic nervous activity in hypertensive patients with a high-salt intake. It is concluded that benidipine may be useful for improving the development of salt-induced hypertension and its accompanying haemodynamic responses.  相似文献   

7.
RATIONALE: In therapeutic use, amitriptyline, reboxetine and citalopram have all been associated with apparent anticholinergic-like side effects (dry mouth, constipation, etc.), despite the very low antimuscarinic activity of reboxetine and citalopram in vitro. OBJECTIVES: We hypothesised that the spectral analysis of heart rate variability (HRV) might detect differences between amitriptyline, citalopram and reboxetine in their anticholinergic activities following a single peroral administration. METHODS: In this double-blind, cross-over study, amitriptyline (75 mg), citalopram (20 mg), reboxetine (4 mg) and placebo were randomly given at 1-week intervals to eight healthy male volunteers. Drug and catecholamine concentrations in plasma were determined repeatedly. The drug effect was assessed with periodic recordings of electrocardiogram (ECG) and blood pressure, and with measurements of salivary secretion. The ECG recordings were subjected to spectral analysis of HRV, in which the high frequency (HF) power of R-R interval (RRI) variability was supposed to reflect cardiac parasympathetic tone. RESULTS: Reboxetine increased heart rate and blood pressure and reduced the HF power of RRI and 3,4-dihydroxyphenylglycol (DHPG) plasma concentrations. Amitriptyline diminished salivary secretion and had a prominent sedative action. Measurements after citalopram did not differ significantly from placebo. CONCLUSIONS: Reboxetine, despite its low antimuscarinic activity in vitro, had distinct effects on the HF power of RRI, consistent with anticholinergic activity in vivo. Amitriptyline had a measurable anticholinergic effect in the salivary glands, but, surprisingly, not in the heart. We suggest that the sedative effect of amitriptyline could alter cardiac sympathovagal balance and, therefore, counteract the anticholinergic drug effect.  相似文献   

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A dihydropyridine calcium (Ca) antagonist, azelnidipine (CAS 123524-52-7, Calblock), exhibits hypotensive effects for a prolonged duration, and has been reported to have a strong antiarteriosclerotic action due to its high affinity for vascular tissues and antioxidative action. It has also been reported that azelnidipine does not cause tachycardia associated with the baroreceptor reflex due to vasodilatation. In this study, the antiarteriosclerotic and cardiac hypertrophy-inhibitory effects, and the autonomic nervous activity in essential hypertension of azelnidipine were investigated. The study was performed using the following 2 protocols: 1) Pulse wave velocity (PWV), carotid arterial intima media thickness (IMT), echocardiography, high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), adiponectin, brain natriuretic peptide (BNP), and 8-isoprostane were measured after an initial treatment with azelnidipine. 2) The treatment was switched to azelnidipine in patients who had previously been under treatment with amlodipine for essential hypertension, and 123I-metaiodobenzylguanidine myocardial scintigraphy (123I-MIBG), measurements of plasma norepinephrine, atrial natriuretic peptide (ANP), and BNP, Holter electrocardiography, and heart rate variability analysis were performed. PWV, IMT, hs-CRP, IL-6, and TNF-alpha significantly decreased. The levels of 8-isoprostane, an antioxidative marker, were also significantly decreased, while adioponectin levels were significantly increased after the initial treatment with azelnidipine. After switching from amlodipine, azelnidipine exhibited a hypotensive effects comparable to amlodipine, and significantly decreased heart rate and the total number of extrasystoles. Noradrenaline levels and the LF/HF ratio were significantly decreased, and the washout rate was significantly reduced on 123I-MIBG myocardial scintigraphy. These findings suggest that azelnidipine inhibits the enhancement of sympathetic nervous activity and the progression of arteriosclerosis through its antioxidative effects.  相似文献   

11.
Rationale In healthy subjects, cortisol and ACTH secretion are acutely stimulated by reboxetine and inhibited by mirtazapine. However, it was not investigated so far whether reboxetine and mirtazapine may also differ in their impact on hypothalamic-pituitary-adrenocortical (HPA) axis activity in depressed patients and whether these effects are related to clinical outcome.Objectives In the present study, we investigated the impact of 5-week treatment with reboxetine or mirtazapine on the combined dexamethasone suppression/corticotropin releasing hormone (DEX/CRH) test results in depressed patients.Methods Forty drug-free patients suffering from a major depressive episode (Diagnostic and Statistical Manual of Mental Disorders-IV criteria) were treated with either reboxetine (8 mg/day; n=20) or mirtazapine (45 mg/day; n=20) for 5 weeks. Before, after 1 and 5 weeks of therapy, the DEX/CRH test was performed and cortisol and ACTH concentrations were measured.Results During reboxetine treatment, a gradual and significant reduction in HPA axis activity as measured by the DEX/CRH test was seen, which was most pronounced after 5 weeks of treatment. In contrast, mirtazapine significantly reduced the cortisol and ACTH concentrations during the DEX/CRH test within 1 week. However, after 5 weeks of mirtazapine treatment, the cortisol and ACTH responses to the DEX/CRH test partially increased again both in responders and nonresponders.Conclusions This is the first study demonstrating differential effects of various antidepressants on the time course of serial DEX/CRH test results in depressed patients.  相似文献   

12.
We studied the effect of transdermally applied scopolamine (scopolamine-TTS) on autonomic nervous activity during sleep. The double-blind, randomized, crossover study was carried out in six healthy male volunteers by applying 1.5 mg scopolamine-TTS or placebo patch on the retroauricular skin and by monitoring heart rate, cardiac ballistogram, respiration and body movements by using electrocardiogram and static charge sensitive bed.Scopolamine did not decrease the time the subjects desired to sleep (516 min after TTS, 511 min after placebo) or the number of body movements of 3–5 s duration the subjects spontaneously performed during sleep (47 after TTS, 58 after placebo). No adverse effects of scopolamine were reported spontaneously. Scopolamine-TTS slowed the mean heart rate during quiet sleep from 53.2 to 44.9 beats · min–1, and increased the duration of bradycardia in response to body movements (MIB-reflex) from 12.5 to 14.7 s with a significant difference between scopolamine and placebo effects. The bradycardias were not associated with disturbances in cardiorespiratory or central nervous system functions. The cardiac vagomimetic action of scopolamine-TTS could be explained by low plasma drug concentrations (175 pg/ml) primarily blocking only neuronal inhibitory prejunctional muscarinic receptors which regulate acetylcholine release from the autonomic ganglia and parasympathetic nerve-endings.Because of the central role of acetylcholine in the physiological regulation of sleep, the effect of scopolamine-TTS on sleep merits further investigations.  相似文献   

13.
The physiological function of benzodiazepine (BDZ) receptors includes regulation of sleep and neuroendocrine activity. Most of the pharmacological effects of BDZ are blocked by flumazenil. However, recent neurological and behavioral studies suggest that flumazenil has its own central intrinsic activity. This issue was addressed in a study of the sleep EEG and the nocturnal secretion of growth hormone and cortisol in ten normal male controls, who were given flumazenil either alone or in combination with the BDZ agonist midazolam, placebo and midazolam alone. Flumazenil prompted an increase in sleep onset latency, a decrease in slow wave sleep and an increase in wakefulness. Plasma cortisol concentrations after flumazenil administration were lower than after midazolam. Both flumazenil and midazolam decreased nocturnal growth hormone secretion. After simultaneous application of both BDZ receptor ligands the growth hormone blunting was amplified. Our study demonstrates that at the level of the sleep EEG and neuroendocrine activity flumazenil is capable of exerting both agonistic and inverse agonistic or antagonistic effects.Parts of this study were presented at the 69th Meeting of the Deutsche Physiologische Gesellschaft, Freiburg, 6–8 March, 1991  相似文献   

14.
OBJECTIVES: To examine the pharmacokinetic characteristics of the selective norepinephrine reuptake inhibitor, reboxetine, in elderly patients with depression. PATIENTS: Twelve female inpatients (mean age 80 +/- 4 years) with major depressive or dysthymic disorder were enrolled in a 4-week uncontrolled study of oral reboxetine 2-8 mg/day. METHODS: After a one-week washout period, patients were randomized into two groups (groups A and B, n = 6/group). Reboxetine was given twice daily, starting with 2 mg/day during week 1 and increasing by 2 mg/day each week to 8 mg/day in week 4. Pharmacokinetic evaluations were carried out at two dosage levels in each group: at the end of weeks 1 and 3 in group A (2 and 6 mg/day), and at the end of weeks 2 and 4 in group B (4 and 8 mg/day). Blood and urine samples were taken for determination of reboxetine pharmacokinetics. RESULTS: Reboxetine displayed linear pharmacokinetics, with dose-proportional changes, in elderly depressed patients. Mean total urinary recovery ranged from 4.06 to 6.17%. The mean area under the plasma concentration-time curve (AUCtau) and the maximum plasma drug concentration (Cmax) showed considerable variation between patients; at a dosage of 4 mg/day, AUCtau was 1,466-6,866 ngxh/ml and Cmax ranged from 169 to 663 ng/ml. CONCLUSIONS: The pharmacokinetics of reboxetine are linear across the dosage range of 2-8 mg/day in elderly depressed patients, although Cmax and AUCtau values are higher (and more variable) than in young adults. These results support the use of a lower starting dose (4 mg/day) of reboxetine in the elderly.  相似文献   

15.
Eighteen non-pregnant woman complaining about insomnia were polysomnographically investigated for 3 nights with weekly intervals. They received placebo, 2 mg flunitrazepam or 10 mg zolpidem according to a cross-over double blind design. The patients were selected by general practitioners on the basis of subjective complaints. Zolpidem is a recently introduced short-acting imidazopyridine hypnotic, binding to a subunit of the benzodiazepine 1 receptor. Flunitrazepam is a well-known hypnotic, binding to both the benzodiazepine 1 and 2 receptor subtypes. Objective recording did not substantiate the subjective complaint of insomnia. Sleep patterns during placebo differed only little from that expected from age matched healthy persons. Both flunitrazepam and zolpidem significantly shortened sleep onset (5 min of continuous sleep beginning with NREM 1 sleep). The sleep composition following flunitrazepam was characterized by an increase in NREM 2, a prolongation of the time to REM sleep, a reduction of REM sleep and an increase in NREM 3–4 sleep during the first 2 h of sleep. The sleep composition following zolpidem resembled more that seen in persons without sleep complaints. However, as compared to placebo, there was a decrease of the time spent awake during sleep and an increase in NREM 3–4 during the first 2 of sleep.  相似文献   

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Previous studies indicate that selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, fluvoxamine, citalopram and paroxetine, suppress rapid eye movement sleep, and increased nocturnal arousals. There has been no published report of the impact of sertraline on the sleep of depressed patients. This study examines such effects. Forty-seven patients with major depressive disorder, randomized to double-blind treatment with sertraline or placebo, completed sleep studies before and after 12 weeks of pharmacotherapy. Groups were compared using multivariate analyses of covariance and/or analyses of covariance to examine 4 empirically defined sets of sleep measures. Compared to the placebo-treated group, patients who received sertraline experienced an increase in delta wave sleep in the first sleep cycle and prolonged rapid eye movement (REM) sleep latency. Although, sertraline therapy decreased the average number of REM periods (from 3.86 to 2.40), the activity of both REM period 1 and REM period 2 was significantly increased. Aside from an increase in sleep latency, sertraline therapy was not associated with a worsening of measures of sleep continuity. There was also no significant difference between the groups on a measure of subjective sleepiness. These findings are both similar and different from those observed in previous studies of other SSRIs. The increase in delta sleep ratio and consolidation of REM sleep may have some other clinical implications. However, the generalizability of these findings is limited because of a number of reasons. Further studies are needed to examine the effects of SSRIs in acute treatment of depressed patients with severe insomnia, and the relationship of acute changes and relapse prevention of recurrent depression.  相似文献   

18.
目的 探讨噻托溴铵联合茶碱缓释片对稳定期COPD患者夜间睡眠低氧的疗效.方法 随机选择2015年3月至2016年3月本院收治的慢性阻塞性肺疾病睡眠低氧患者82例作为本次研究对象,将其平均分为对照组41例和观察组41例.对照组噻托溴铵治疗,观察组噻托溴铵联合茶碱缓释片治疗,观察比较两组夜间睡眠血氧饱和度、血气分析及肺功能指标.结果 观察组治疗后夜间睡眠血氧饱和度与治疗前比较,差异具有统计学意义(均P< 0.05);治疗后,观察组夜间睡眠血氧饱和度与对照组比较,差异具有统计学意义(均P< 0.05).观察组治疗后血气分析与治疗前比较,差异具有统计学意义(P< 0.05)治疗后,观察组和对照组血气分析比较,差异具有统计学意义(均P< 0.05).观察组治疗后肺功能与治疗前比较,差异具有统计学意义(均P< 0.05);治疗后,观察组肺功能与对照组比较,差异具有统计学意义(均P< 0.05).结论 噻托溴铵联合茶碱缓释片可进一步改善稳定期COPD患者的夜间睡眠低氧、血气分析和肺功能,且安全性高.  相似文献   

19.
This review focuses on recent literature concerning dysthymia in the elderly population. Epidemiological data and clinical picture, diagnostic and therapeutic issues are evaluated and discussed. Although depressive syndromes are common in older patients, prevalence rates of dysthymia in the elderly are lower than in younger adults. This finding may be the consequence of the diagnostic criteria provided by the Diagnostic and Statistical Manual of Mental Disorders (DSM) which are not specific for older adults. Other factors that complicate making diagnoses of dysthymia in older individuals are comorbid general conditions, cognitive deterioration and disorders, and frequent adverse life events (e.g. bereavement). The effects of these factors should be better defined to clarify whether elderly dysthymia is underestimated and if modified diagnostic criteria should be provided. A few researchers have identified a series of clinical features that are clearly different in the elderly and in young adult patients with dysthymia. These features are particularly related to the late onset and to the peculiar comorbidity of this disorder and suggest that dysthymia is a different disorder in the elderly. Drug treatment of depressive conditions in the elderly is currently based on new antidepressants [selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors, norepinephrine (noradrenaline) reuptake inhibitors, benzamides]. These agents have an improved adverse effect profile compared with some of the older agents. Moreover, very few systematic studies have been performed using these drugs in samples of older patients with dysthymia and available data do not allow conclusions on drug choice and dosage. Besides, no specific data are available concerning the psychotherapy of dysthymia in this age group. All these topics need to be further investigated in studies comparing the elderly with control groups of younger patients with dysthymia.  相似文献   

20.
We examined the effectiveness of reboxetine, a norepinephrine reuptake inhibitor (NRI), compared with placebo for the treatment of patients with severe major depression (defined as a score on the 17-item Hamilton Rating Scale for Depression [HAM-D] >/=25). Data were obtained from four prospective, double-blind, randomized, placebo-controlled clinical trials of the efficacy of reboxetine (8 to 10 mg/d) over 4 to 8 weeks in patients with major depression. In three of the trials, reboxetine produced a significantly greater reduction than placebo in mean HAM-D scores from baseline to the last clinical assessment (p < 0.001). There were significantly more responders to treatment (defined as a reduction in HAM-D score >50% between baseline and the last follow-up observation) treated with reboxetine than placebo in three trials. The overall mean responder rate with reboxetine was 63% (range: 56-74%) compared with 36% (range: 20-52%) with placebo. These results demonstrate that reboxetine is significantly more effective than placebo in a subgroup of patients with severe depression.  相似文献   

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