Introduction: Allostatic load (AL) index proposes indicators for the functioning of the main potentially stress-affected systems. Sex differences in stress response and stress-related diseases susceptibility have been...Introduction: Allostatic load (AL) index proposes indicators for the functioning of the main potentially stress-affected systems. Sex differences in stress response and stress-related diseases susceptibility have been described for the general population. In this observational study we describe the effects of sex and age on AL variables, in a cohort of patients with general anxiety disorders and neuroticism treated with alprazolam during 12 weeks, before and after treatment. Methods: Patients with general (DSM IV) anxiety disorders with >6 in Hamilton scale, AL (>1 Crimmins and Seeman AL modified criteria) and neuroticism >18 (NEO-FFI inventory), were included. All patients completed psychiatric assessment, AL index determination before (−1 week) and after 12 weeks of treatment with alprazolam (0.25 - 1 mg/t.i.d). Allostatic load parameters comprised cardiovascular, metabolic and inflammatory variables. Univariate analysis (two-way ANOVA), Student’s t-test (related variables) and Pearson correlations were determined. Results: Fifty-four patients, 35 females (48.6 ± 11.7 years) and 19 males (44.2 ± 12.8 years) with general anxiety disorder were included;28 patients with Conclusions: In this preliminary analysis we described sex and age differences in psychiatry aspects and AL indexes in patients with general anxiety disorders in the short-term treatment with alprazolam. These considerations remark the need of pondering sex and age differences during the use of drugs for protracted periods.展开更多
On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated ...On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines”. With this announcement, the FDA proclaimed that much more needs to be known about the initiation, continuation, and discontinuation of these widely-used drugs. Unfortunately, relevant information is lacking, since for many years, there has been a notable sparsity in the funding and conduct of basic and clinical research on these drugs. In order to begin to fill the void, it is valuable to (re)examine animal models. We here describe a model of conditioned place-preference (CPP) for rats and for the first time, to our knowledge, show that the representative benzodiazepine alprazolam induces positive place-preference in male rats.展开更多
Objective: To explore the effect of trimebutine in combined with alprazolam on the gastrointestinal hormones and living quality in patients with diarrhea-type IBS (IBS-D). Methods: A total of 117 patients with IBS-D w...Objective: To explore the effect of trimebutine in combined with alprazolam on the gastrointestinal hormones and living quality in patients with diarrhea-type IBS (IBS-D). Methods: A total of 117 patients with IBS-D who were admitted in our hospital were included in the study and randomized into the control group (n=58) and the treatment group (n=59). The patients in the control group were given trimebutine;while the patients in the treatment group were given trimebutine in combined with alprazolam. The patients in the two groups were continuously treated for 4 weeks. The levels of gastrointestinal hormones and brain-gut peptide before and after treatment in the two groups were detected and compared. SF-36 was used to analyze the living quality before and after treatment in the two groups. Results: MOT;GAS;SP;and 5-HT levels after treatment in the two groups were significantly reduced;while VIP;SS;CCK;and CGRP levels and SF-36 score in each dimension were significantly elevated;and the comparison between the two groups was statistically significant. Conclusions:Trimebutine in combined with alprazolam in the treatment of IBS-D can significantly improve the gastrointestinal hormones and brain-gut peptide;and enhance the living quality;with a significant efficacy.展开更多
Objective To compare the pharmacokinetics of Alprazolam after intranasal and intragastic administration in rats and evaluate the practicability of Alprazolam as a nasal drug delivery system.Methods 12 rats were random...Objective To compare the pharmacokinetics of Alprazolam after intranasal and intragastic administration in rats and evaluate the practicability of Alprazolam as a nasal drug delivery system.Methods 12 rats were randomly divided into two groups.The fate of drug in the serum of rats was monitered after intranasal and intragastic administration of Alprazolam 2 mg·kg-1.Serum levels of Alprazolam were determined by reversed-phase HPLC with Diode array detectors(DAD).Chromatographic conditions were adopted with ODS column as solid phase,methanaol-0.02 M ammonium acetate(pH=5.0)(60∶40)as mobile phase at a flow rate of 1.0 mL·min-1.The detection wavelength was 223 nm.The concentration-time data were analyzed using 3P87 program,and the pharmacokinetic parameters were compared by t-test.Results The pharmacokinetic characteristics were fit to two and one compartment opened model after intranasal and intragastic administration of Alprazolam,respectively.The drug absorption was quicker and the serum concentrations of Alprazolam was significantly higher in rats after intranasal administration group than that intragastic administration group(P<0.05).The eliminate parameters between the two groups were no significant difference(P>0.05).Means of pharmacokinetic parameters in intranasal and intragastic groups were:Ka 37.35±22.98 vs 11.57±12.47 h-1(P<0.05),t1/2ka0.025±0.013 vs 0.156±0.122 h(P<0.05),β(Ke)0.3131±0.1194 vs 0.3091±0.1216 h-1(P>0.05),t1/2β(t1/2Ke)2.51±0.99 vs 2.54±0.97 h(P>0.05),tmax 0.156±0.069 vs 0.618±0.414 h(P<0.01),Cmax 353.11±96.30 vs 62.09±35.08 μg·L-1(P<0.01),AUC 1111.6±473.2 vs 274.1±185.3 μg·L-1·h(P<0.01).Conclusions Alprazolam was absorbed quickly in rats after intranasal administration.And the serum concentration and bioavailability can be significantly increased after intranasal administration,which may be an effective preparation as nasal drug delivery system.展开更多
<span lang="EN-US" style="white-space:normal;font-family:Verdana;">The benzodiazepines were introduced into medical practice during the 1960s. At the time, they represented a safer alternativ...<span lang="EN-US" style="white-space:normal;font-family:Verdana;">The benzodiazepines were introduced into medical practice during the 1960s. At the time, they represented a safer alternative to extant therapies used for anxiety, such as the barbiturates. However, on September 23, 2020, the United States FDA indicated that more is needed to be known about the initiation, continuation, and discontinuation of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">the </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">us</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">e of</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> these widely-used drugs with publication of the announcement </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">“</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">to address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines.</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">”</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> Because for many years</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">, </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">there has been a sparsity </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">research on these drugs, relevant information is unfortunately lacking at this critical time. It is therefore valuable to (re)establish animal models and begin to collect relevant data. We here use a model of conditioned place</span><span lang="EN-US" style="white-space:normal;" "=""> </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">preference (CPP) </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">which </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">suggests that the representative benzodiazepine alprazolam induces positive place preference in female rats.</span>展开更多
文摘Introduction: Allostatic load (AL) index proposes indicators for the functioning of the main potentially stress-affected systems. Sex differences in stress response and stress-related diseases susceptibility have been described for the general population. In this observational study we describe the effects of sex and age on AL variables, in a cohort of patients with general anxiety disorders and neuroticism treated with alprazolam during 12 weeks, before and after treatment. Methods: Patients with general (DSM IV) anxiety disorders with >6 in Hamilton scale, AL (>1 Crimmins and Seeman AL modified criteria) and neuroticism >18 (NEO-FFI inventory), were included. All patients completed psychiatric assessment, AL index determination before (−1 week) and after 12 weeks of treatment with alprazolam (0.25 - 1 mg/t.i.d). Allostatic load parameters comprised cardiovascular, metabolic and inflammatory variables. Univariate analysis (two-way ANOVA), Student’s t-test (related variables) and Pearson correlations were determined. Results: Fifty-four patients, 35 females (48.6 ± 11.7 years) and 19 males (44.2 ± 12.8 years) with general anxiety disorder were included;28 patients with Conclusions: In this preliminary analysis we described sex and age differences in psychiatry aspects and AL indexes in patients with general anxiety disorders in the short-term treatment with alprazolam. These considerations remark the need of pondering sex and age differences during the use of drugs for protracted periods.
文摘On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines”. With this announcement, the FDA proclaimed that much more needs to be known about the initiation, continuation, and discontinuation of these widely-used drugs. Unfortunately, relevant information is lacking, since for many years, there has been a notable sparsity in the funding and conduct of basic and clinical research on these drugs. In order to begin to fill the void, it is valuable to (re)examine animal models. We here describe a model of conditioned place-preference (CPP) for rats and for the first time, to our knowledge, show that the representative benzodiazepine alprazolam induces positive place-preference in male rats.
文摘Objective: To explore the effect of trimebutine in combined with alprazolam on the gastrointestinal hormones and living quality in patients with diarrhea-type IBS (IBS-D). Methods: A total of 117 patients with IBS-D who were admitted in our hospital were included in the study and randomized into the control group (n=58) and the treatment group (n=59). The patients in the control group were given trimebutine;while the patients in the treatment group were given trimebutine in combined with alprazolam. The patients in the two groups were continuously treated for 4 weeks. The levels of gastrointestinal hormones and brain-gut peptide before and after treatment in the two groups were detected and compared. SF-36 was used to analyze the living quality before and after treatment in the two groups. Results: MOT;GAS;SP;and 5-HT levels after treatment in the two groups were significantly reduced;while VIP;SS;CCK;and CGRP levels and SF-36 score in each dimension were significantly elevated;and the comparison between the two groups was statistically significant. Conclusions:Trimebutine in combined with alprazolam in the treatment of IBS-D can significantly improve the gastrointestinal hormones and brain-gut peptide;and enhance the living quality;with a significant efficacy.
文摘Objective To compare the pharmacokinetics of Alprazolam after intranasal and intragastic administration in rats and evaluate the practicability of Alprazolam as a nasal drug delivery system.Methods 12 rats were randomly divided into two groups.The fate of drug in the serum of rats was monitered after intranasal and intragastic administration of Alprazolam 2 mg·kg-1.Serum levels of Alprazolam were determined by reversed-phase HPLC with Diode array detectors(DAD).Chromatographic conditions were adopted with ODS column as solid phase,methanaol-0.02 M ammonium acetate(pH=5.0)(60∶40)as mobile phase at a flow rate of 1.0 mL·min-1.The detection wavelength was 223 nm.The concentration-time data were analyzed using 3P87 program,and the pharmacokinetic parameters were compared by t-test.Results The pharmacokinetic characteristics were fit to two and one compartment opened model after intranasal and intragastic administration of Alprazolam,respectively.The drug absorption was quicker and the serum concentrations of Alprazolam was significantly higher in rats after intranasal administration group than that intragastic administration group(P<0.05).The eliminate parameters between the two groups were no significant difference(P>0.05).Means of pharmacokinetic parameters in intranasal and intragastic groups were:Ka 37.35±22.98 vs 11.57±12.47 h-1(P<0.05),t1/2ka0.025±0.013 vs 0.156±0.122 h(P<0.05),β(Ke)0.3131±0.1194 vs 0.3091±0.1216 h-1(P>0.05),t1/2β(t1/2Ke)2.51±0.99 vs 2.54±0.97 h(P>0.05),tmax 0.156±0.069 vs 0.618±0.414 h(P<0.01),Cmax 353.11±96.30 vs 62.09±35.08 μg·L-1(P<0.01),AUC 1111.6±473.2 vs 274.1±185.3 μg·L-1·h(P<0.01).Conclusions Alprazolam was absorbed quickly in rats after intranasal administration.And the serum concentration and bioavailability can be significantly increased after intranasal administration,which may be an effective preparation as nasal drug delivery system.
文摘<span lang="EN-US" style="white-space:normal;font-family:Verdana;">The benzodiazepines were introduced into medical practice during the 1960s. At the time, they represented a safer alternative to extant therapies used for anxiety, such as the barbiturates. However, on September 23, 2020, the United States FDA indicated that more is needed to be known about the initiation, continuation, and discontinuation of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">the </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">us</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">e of</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> these widely-used drugs with publication of the announcement </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">“</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">to address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines.</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">”</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> Because for many years</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">, </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">there has been a sparsity </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">research on these drugs, relevant information is unfortunately lacking at this critical time. It is therefore valuable to (re)establish animal models and begin to collect relevant data. We here use a model of conditioned place</span><span lang="EN-US" style="white-space:normal;" "=""> </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">preference (CPP) </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">which </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">suggests that the representative benzodiazepine alprazolam induces positive place preference in female rats.</span>