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Macrolide-Clarithromycin Task-Force for the Treatment and Prophylaxis of Covid-19 as a Single Agent 大环内酯-克拉霉素单药治疗和预防Covid-19工作组
Pub Date : 2020-06-18 DOI: 10.4236/pp.2020.116009
E. Mansilla, R. Martínez, G. Marín, I. Filho, E. Rivas, Jaime Rivas, K. Carvalho, M. Dayer, Ali Samadikuchaksaraei
SARS-CoV-2 is a novel RNA coronavirus responsible of a deadly pandemic: the clinical illness COVID-19. With only one authorized drug for emergency use in critically ill patients: Remdesivir, there is not any other approved drug or vaccine yet with proven potential to overcome this infection. We exposed here many scientific evidences to support our novel idea that a macrolide, basically Clarithromycin, could be effective as a single agent for treatment and prophylaxis of COVID-19. Clarithromycin could change the history of this pandemic. It could reduce the costs of treatment and the potential adverse effects when combining more than one drug such as with Hydroxychloroquine. Clarithromycin treatment and prophylaxis as a single agent could be much more simple, safe and cheaper as giving Chloroquine or Hydroxychloroquine alone or in combination with Azithromycin as well as other therapeutic options.
SARS-CoV-2是一种新型RNA冠状病毒,导致致命的大流行:临床疾病COVID-19。由于只有一种获批用于危重患者的紧急药物:Remdesivir,目前还没有任何其他获批的药物或疫苗被证明具有克服这种感染的潜力。我们在这里展示了许多科学证据来支持我们的新想法,即大环内酯类药物,基本上是克拉霉素,可以作为一种有效的单一药物治疗和预防COVID-19。克拉霉素可能改变这种大流行的历史。它可以降低治疗成本,并减少与一种以上药物(如与羟氯喹)联合使用时的潜在副作用。克拉霉素治疗和预防作为一种单一药物可能比单独使用氯喹或羟氯喹或与阿奇霉素以及其他治疗方案联合使用更简单、更安全、更便宜。
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引用次数: 1
E-Cigarette Survey among Student Pharmacists Reveals Troubling Results 对学生药剂师的电子烟调查显示了令人不安的结果
Pub Date : 2020-06-05 DOI: 10.4236/pp.2020.116012
Jamie L. McConaha, Phil Lunney, J. Kitzen, J. Pergolizzi, Robert W. Taylor, R. Raffa
The rise in “vaping”-associated deaths in the United States raises serious concerns. A justification for some level of risk is that e-cigarettes might provide a “reverse-gateway” from smoking traditional cigarettes to a less-harmful alternative. But are users actually smokers? We developed an electronic on-line survey to gather data regarding e-cigarette usage in a target study population of pharmacy students. The survey was created using Google Forms to collect the responses anonymously. We surveyed medical-savvy healthcare students about their e-cigarette use, and whether or not their healthcare providers were aware of their e-cigarette use. Although nearly one-fourth of a convenience sampling of 134 pharmacy-student respondents (23.9%) reported using e-cigarettes, only 2.0% reported prior regular cigarette use, 28% used cartridges containing nicotine and only 11.2% had tried and wanted to quit. The majority (64.1%) reported that their healthcare providers did not ask about such use, and respondents did not volunteer this information. The results of this pilot survey reveal a significant e-cigarette use among health-aware pharmacy students, and they do not support the notion that the respondents do so to quit smoking. The observation that most of the students’ healthcare providers did not inquire about their e-cigarette use, coupled with the finding that users did not volunteer their vaping behavior, suggests that the information should be included when getting a medical history. Further research is needed to determine what behavioral factors may play a role in this type of decision-making among student healthcare professionals.
在美国,与“电子烟”相关的死亡人数的上升引发了严重的担忧。存在一定程度风险的理由是,电子烟可能提供了从吸传统香烟到危害较小的替代品的“反向通道”。但使用者真的是吸烟者吗?我们开发了一项电子在线调查,以收集有关药学学生目标研究人群中电子烟使用情况的数据。该调查使用谷歌表格匿名收集回复。我们调查了精通医疗保健的学生使用电子烟的情况,以及他们的医疗服务提供者是否意识到他们使用电子烟。在134名受访的药学专业学生中,尽管近四分之一(23.9%)的受访者表示使用电子烟,但只有2.0%的人表示以前经常使用香烟,28%的人使用含有尼古丁的烟盒,只有11.2%的人尝试过并想要戒烟。大多数人(64.1%)报告说,他们的医疗保健提供者没有询问这种使用情况,受访者也没有自愿提供这些信息。这项试点调查的结果显示,在有健康意识的药学专业学生中,电子烟的使用率很高,他们不支持受访者这样做是为了戒烟的观点。观察到大多数学生的医疗保健提供者没有询问他们的电子烟使用情况,再加上发现用户没有自愿提供他们的电子烟行为,这表明在获得病史时应该包括这些信息。需要进一步的研究来确定哪些行为因素可能在学生医疗保健专业人员的这种决策中发挥作用。
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引用次数: 1
“Atropisomeric” Drugs: Basic Concept and Example of Application to Drug Development “atrosomomer”药物:基本概念及在药物开发中的应用实例
Pub Date : 2020-01-06 DOI: 10.4236/pp.2020.111001
R. Raffa, J. Pergolizzi, Robert Taylor
Many therapeutic drugs are racemates; i.e. they are chiral molecules consisting of “left”- and “right-handed” enantiomers (stereoisomers that are mirror images of each other, and are non-superimposable). In some cases, both enantiomers of the drug contribute to some extent (or equally) to the therapeutic effect; in other cases they contribute not at all. The same is true for the adverse effects of racemate drugs: the adverse effects of a racemate drug can be greater-than, less-than, or equal to one or the other enantiomer. An unusual situation arises when a drug consists of “atropisomers”, stereoisomers arising because of hindered rotation about a single chemical bond. We summarize the concept of atropisomerism, and give examples.
许多治疗药物是外消旋物;也就是说,它们是手性分子,由“左”和“右手”对映体(互为镜像的立体异构体,不可重叠)组成。在某些情况下,药物的两种对映体在一定程度上(或同等程度)有助于治疗效果;在其他情况下,它们根本没有贡献。外消旋体药物的副作用也是如此:外消旋体药物的副作用可能大于、小于或等于一种或另一种对映体。当一种药物由“反旋异构体”组成时,就会出现一种不寻常的情况,这种立体异构体是由于单个化学键的旋转受阻而产生的。我们总结了收缩异构的概念,并举例说明。
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引用次数: 4
Improvement of Dissolution Rate of Gliclazide Using Solid Dispersions with Aerosil 380 and Its Effect on Alloxan Induced Diabetic Rats Aerosil 380固体分散体提高格列齐特溶出率及其对四氧嘧啶诱导的糖尿病大鼠的影响
Pub Date : 2019-08-07 DOI: 10.4236/PP.2019.108030
S. Paul, Md. Nur Islam, Md. Ashraf Ali, R. Barman, M. I. I. Wahed, B. M. Rahman
The main objective of this research is to conduct a comprehensive study for enhancing the aqueous solubility of poorly water soluble gliclazide using hydrophilic fumed silica particles (Aerosil® 380) and evaluating the influence of silica on drug release profile and pharmacological activity on alloxan induced diabetic rats. Solid dispersions (SD’s) of gliclazide were prepared using solvent evaporation method. The dissolution profiles and solid state characterization of the SD’s prepared were all evaluated. The dissolution rate of gliclazide in the SD’s with fumed silica (weight ratio, 1:1) was approximately 38%, which is about 10 fold higher than that of the pure drug after 30 min. After forming the SD’s, gliclazide changed into an amorphous state, which can infer from differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Fourier transform infrared spectroscopy (FTIR) also revealed the formation of weak hydrogen bonding through the interactions between the secondary amine groups of gliclazide and silanol groups of silica particles in the SD’s. The rapid dissolution rate from the SD’s might be attributed to the amorphization of drug, improved specific surface area and wettability than the original drug crystals. Further, we investigated the antidiabetic effects of SD’s of gliclazide in alloxan induced diabetic rats. The SD’s of gliclazide decrease the blood glucose level 64% whereas the conventional gliclazide decreases only 37% in diabetic rats. Lipid profiles, kidney and liver functions are remarkably improved in diabetic rat treated with SD’s of gliclazide than that of conventional gliclazide. These results suggest that SD’s of gliclazide have much more bioavailability and hence are more pharmacologically active than that of conventional gliclazide form.
本研究的主要目的是利用亲水性气相二氧化硅颗粒(Aerosil®380)增强难水溶性格列齐特的水溶性,并评估二氧化硅对四氧嗪诱导的糖尿病大鼠的药物释放谱和药理活性的影响。采用溶剂蒸发法制备了格列齐特的固体分散体。对所制备的SD的溶解谱和固态特性进行了评价。气相二氧化硅(质量比为1:1)在SD中的溶出率约为38%,30 min后比纯药物的溶出率高约10倍。通过差示扫描量热法(DSC)和粉末x射线衍射(PXRD)可以推断,格列齐特在SD形成后变为无定形状态。傅里叶变换红外光谱(FTIR)还揭示了格列齐特的仲胺基与硅烷醇基之间的相互作用形成弱氢键。SD的快速溶解可能是由于药物的非晶化,比表面积和润湿性比原始药物晶体有所提高。进一步观察格列齐特SD对四氧嘧啶诱导的糖尿病大鼠的降糖作用。格列齐特的SD能使糖尿病大鼠的血糖水平降低64%,而普通格列齐特只降低37%。与普通格列齐特组相比,格列齐特组对糖尿病大鼠的血脂、肾功能和肝功能有显著改善。这些结果表明,格列齐特的SD具有更高的生物利用度,因此比传统形式的格列齐特具有更高的药理活性。
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引用次数: 4
TNF Type-I Receptor Inhibitor, R-7050 Attenuates Acute Kidney Injury in a Mouse Model of Crush Syndrome TNF - 1型受体抑制剂R-7050在挤压综合征小鼠模型中减轻急性肾损伤
Pub Date : 2018-12-29 DOI: 10.4236/PP.2018.912043
S. Mizuno, E. Osaki, Hiroyuki Ohnishi
Crush syndrome (CS) is caused by severe and extensive muscular skeletal damages, and acute kidney injury (AKI) with hyperkalemia is one of the most lethal factors of this syndrome. Especially under natural disasters of earthquake, many persons die due to AKI and hyperkalemia-induced cardiac arrest, but there has been no pathogenesis-based drugs for preventing CS-induced AKI. Pro-inflammatory cytokines, such as TNF-α and IL-6, play a critical role for induction of AKI during CS development. Glycerol-injected mice are used as an experimental tool for reflecting pathological events of human CS. Using this popular model, we provide evidence to show that TNF type-I receptor (TNFR1) inhibitor, R-7050 significantly attenuates the onset of AKI after the muscular destruction. In this process, R-7050 treatment suppressed the NF-κB activation in the affected kidney, and this was associated with a decrease in blood IL-6, a downstream target of NF-κB. As a result, renal tubular apoptosis became milder in the R-7050-treated CS mice. These findings suggest that induction of IL-6 via sequential events of TNF-α a TNFR1 a NF-κB is contributable for renal tubular apoptosis, a histological hallmark of AKI. Thus, TNFR1-selective inhibition can be a pharmacological strategy to attenuate the onset of AKI immediately after the clinical manifestation of rhabdomyolysis.
挤压综合征(CS)是由严重和广泛的肌肉骨骼损伤引起的,急性肾损伤(AKI)伴高钾血症是该综合征最致命的因素之一。特别是在地震等自然灾害下,许多人死于高钾血症引起的AKI和心脏骤停,但目前还没有基于发病机制的药物来预防cs引起的AKI。促炎细胞因子,如TNF-α和IL-6,在CS发展过程中对AKI的诱导起关键作用。用注射甘油的小鼠作为反映人类CS病理事件的实验工具。使用这个流行的模型,我们提供证据表明TNF - 1型受体(TNFR1)抑制剂R-7050显著减轻肌肉破坏后AKI的发作。在这个过程中,R-7050治疗抑制了受影响肾脏中NF-κB的活化,这与NF-κB的下游靶点IL-6的降低有关。结果,r -7050处理的CS小鼠肾小管凋亡变轻。这些发现表明,通过TNF-α、TNFR1和NF-κB的序列事件诱导IL-6参与肾小管凋亡,肾小管凋亡是AKI的组织学标志。因此,tnfr1选择性抑制可作为在横纹肌溶解临床表现后立即减轻AKI发作的药理学策略。
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引用次数: 0
Antioxidant and Cytotoxicity Potential of Six Synthesized Chalcones 六种合成查尔酮的抗氧化和细胞毒性
Pub Date : 2018-12-26 DOI: 10.4236/PP.2018.912042
S. Kouakou, M. Ouattara, J. P. N'Guessan, S. Coulibaly, A. G. Irié-N’guessan, G. Kouakou-Siransy
Background: Chalcones are open-chain flavonoids which display a large number of pharmacological activities such as cytotoxic, anti-inflammatory including antioxidant. The objective of this study was to assess antioxidant and cytotoxic activity of six synthesized chalcones. Methodology: For the current experiments, 1,3-diphenylpropenone (compound R) was used as molecular model to synthetize six compounds, namely three benzyl-benzimidazolyl-chalcones (U1, U2, WAC1) and three imidazopyridinyl-chalcones (V1, V2, V3). All the compounds were evaluated for their ability to scavenge the stable free ABTS.+ radical cation, according to the method develop by Choong et al. In addition, the cytotoxicity test described by Price et al., was performed using healthy human cell line, then in human malignant cell lines (HEP-2, A549). Results: All synthesized chalcones reduced the ABTS.+ radical cation. Indeed, benzyl benzimidazolyl compounds WAC1, U1, U2, by developing respectively 39.61%, 66.09%, and 84.20% percentages of reduction, showed an antioxidant effect 6, 11 and 14 times greater than the compound R (6.14%). As a result, imidazopyridinyl-chalcones compounds, namely V1, V2 and V3 reduced the ABTS.+ radical cation at 91.62%, 99.84% and 97.45% respectively, being 15 and 16 times more active than the compound R. About cytotoxicity, V2 inhibited not significantly HEP-2 malignant cells growth at 48.64%, compared to the standard product, i.e. doxorubicin that inhibited the growth of the same cells at 42.37%. WAC1 inhibited significantly the growth of A549 malignant cells at 89.53%, more than doxorubicin which percentage of growth inhibition was 71.58%. Conclusion: The presence of the α, β-unsaturated carbonyl system (or 1,3-diphenylpropenone) along with a benzimidazole or imidazopyridine heterocyclic ring is likely to contribute to both cytotoxic and antioxidant activities of these compounds.
背景:查尔酮是一种开链类黄酮,具有细胞毒、抗炎、抗氧化等多种药理活性。本研究的目的是评估六种合成查尔酮的抗氧化和细胞毒活性。方法:本实验以1,3-二苯丙烯(化合物R)为分子模型,合成了3个苯并咪唑查尔酮(U1、U2、WAC1)和3个咪唑吡啶查尔酮(V1、V2、V3) 6个化合物。所有化合物对稳定游离ABTS的清除能力进行了评价。+自由基阳离子,根据Choong等人开发的方法。此外,Price等人描述的细胞毒性试验先用健康的人类细胞系进行,然后用人类恶性细胞系(HEP-2, A549)进行。结果:所有合成的查尔酮均能降低ABTS。+自由基阳离子。苯并咪唑类化合物WAC1、U1和U2的还原率分别为39.61%、66.09%和84.20%,其抗氧化效果分别是化合物R(6.14%)的6倍、11倍和14倍。因此,咪唑吡啶查尔酮化合物V1、V2和V3降低了ABTS。+自由基阳离子的活性分别为91.62%、99.84%和97.45%,是化合物r的15倍和16倍。在细胞毒性方面,V2对HEP-2恶性细胞的抑制作用为48.64%,而标准品阿霉素对HEP-2恶性细胞的抑制作用为42.37%。WAC1对A549恶性细胞的生长抑制率为89.53%,明显高于阿霉素的71.58%。结论:α, β-不饱和羰基体系(或1,3-二苯丙烯)与苯并咪唑或咪唑吡啶杂环的存在可能有助于这些化合物的细胞毒性和抗氧化活性。
{"title":"Antioxidant and Cytotoxicity Potential of Six Synthesized Chalcones","authors":"S. Kouakou, M. Ouattara, J. P. N'Guessan, S. Coulibaly, A. G. Irié-N’guessan, G. Kouakou-Siransy","doi":"10.4236/PP.2018.912042","DOIUrl":"https://doi.org/10.4236/PP.2018.912042","url":null,"abstract":"Background: Chalcones are open-chain flavonoids which display a large number of pharmacological activities such as cytotoxic, anti-inflammatory including antioxidant. The objective of this study was to assess antioxidant and cytotoxic activity of six synthesized chalcones. Methodology: For the current experiments, 1,3-diphenylpropenone (compound R) was used as molecular model to synthetize six compounds, namely three benzyl-benzimidazolyl-chalcones (U1, U2, WAC1) and three imidazopyridinyl-chalcones (V1, V2, V3). All the compounds were evaluated for their ability to scavenge the stable free ABTS.+ radical cation, according to the method develop by Choong et al. In addition, the cytotoxicity test described by Price et al., was performed using healthy human cell line, then in human malignant cell lines (HEP-2, A549). Results: All synthesized chalcones reduced the ABTS.+ radical cation. Indeed, benzyl benzimidazolyl compounds WAC1, U1, U2, by developing respectively 39.61%, 66.09%, and 84.20% percentages of reduction, showed an antioxidant effect 6, 11 and 14 times greater than the compound R (6.14%). As a result, imidazopyridinyl-chalcones compounds, namely V1, V2 and V3 reduced the ABTS.+ radical cation at 91.62%, 99.84% and 97.45% respectively, being 15 and 16 times more active than the compound R. About cytotoxicity, V2 inhibited not significantly HEP-2 malignant cells growth at 48.64%, compared to the standard product, i.e. doxorubicin that inhibited the growth of the same cells at 42.37%. WAC1 inhibited significantly the growth of A549 malignant cells at 89.53%, more than doxorubicin which percentage of growth inhibition was 71.58%. Conclusion: The presence of the α, β-unsaturated carbonyl system (or 1,3-diphenylpropenone) along with a benzimidazole or imidazopyridine heterocyclic ring is likely to contribute to both cytotoxic and antioxidant activities of these compounds.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":"82 1","pages":"536-546"},"PeriodicalIF":0.0,"publicationDate":"2018-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76884649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Study of Factors Affecting Medical Incident: 1. Dispensing 医疗事故影响因素研究:调剂
Pub Date : 2018-12-20 DOI: 10.4236/PP.2018.912041
Yuka Miyachi, Chika Nakayama, Kazuyo Nagashiba, K. Kinoshita, Masayuki Takeuchi, Masafumi Ohnishi, Hiroko Saito, Taeyuki Oshima
In recent years, medical institutions have taken a variety of measures to prevent medical incident. In addition, progress has been made toward the development of a fully automated system for the purpose of medicine dispensing. However, automating the dispensing, or having it replaced by artificial intelligence (AI) will not, eradicate human error. Thus, measures against human error will continue to serve as an important topic. Therefore, hospitals are required to improve the efficiency of the pharmacy department. For these purposes, attention has now shifted to Supply Processing and Distribution (SPD). In this study, we measured for the gaze of the pharmacist and SPD, and examined the factors affecting dispensing error; moreover, we examined prevention of the human error. In the results of the eye tracking, SPD members tended to spend a greater number of gaze time and gaze counts, for each medicine, on “medicines” and “picking lists,” than pharmacists. On the other hand, when pharmacists picking medicines, they performed various work operations in parallel, such as checking the prescription and looking the next shelf location. It was conjectured that SPD members had more clearly defined items to check when picking, compared to pharmacists. This may have possibly led to a lower chance of dispensing errors being introduced by SPD members. These results suggest that the process of selection is not a mandatory requirement of pharmacists during the action of dispensing. Instead, SPD members, pharmacy assistants, or automatic dispensing devices could serve as substitutes for picking. It is suggested that pharmacists should spend more time and effort on prescription inspection, medicines checking and dosing operations.
近年来,医疗机构采取了多种措施来预防医疗事故。此外,为药品调剂目的的全自动系统的开发也取得了进展。然而,自动化点胶或用人工智能(AI)取代它并不能消除人为错误。因此,防止人为错误的措施将继续是一个重要的话题。因此,要求医院提高药剂科的工作效率。出于这些目的,注意力现在已经转移到供应加工和分销(SPD)。在本研究中,我们测量了药剂师的凝视和SPD,并检查了影响配药误差的因素;此外,我们还研究了人为错误的预防。在眼动追踪的结果中,SPD成员倾向于花更多的凝视时间和凝视次数,对于每种药物,在“药物”和“挑选清单”上比药剂师花更多的时间和次数。另一方面,当药剂师挑选药物时,他们同时进行各种工作操作,例如检查处方和查看下一个货架位置。据推测,与药剂师相比,SPD成员在挑选时有更明确的检查项目。这可能导致SPD成员引入分配错误的可能性较低。这些结果表明,在调剂过程中,选择过程并不是药剂师的强制性要求。相反,SPD成员、药房助理或自动配药设备可以作为采摘的替代品。建议药师在处方审核、验药和给药操作等方面投入更多的时间和精力。
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引用次数: 3
Onset Time Profiles for Syncope Associated with α 1 -Adrenoceptor Blockers in Males: Analysis of a Spontaneous Adverse Drug Event Database 男性与α 1 -肾上腺素受体阻滞剂相关的晕厥发病时间:自发药物不良事件数据库分析
Pub Date : 2018-12-14 DOI: 10.4236/PP.2018.912040
K. Ohyama, Masaya Furumoto, M. Sugiura
Background: α1-Adrenoceptor blockers (α1Bs) are used for the treatment of benign prostatic hyperplasia and hypertension, but they are known to cause hypotension-related adverse events. The objective of the present study was to evaluate the onset time profiles for syncope associated with the use of α1Bs. Methods: We analyzed the data obtained from the Japanese Adverse Drug Event Report (JADER) database for a period from April 2004 until November 2016 and calculated reporting odds ratios (RORs) for eight α1Bs available on the Japanese market, using disproportionality analysis. Moreover, time information recorded in the JADER database was analyzed to evaluate the onset times of adverse events. Results: In total, 186,724 reports for males older than 20 years were analyzed. Significant RORs for syncope, with 95% confidence intervals, were obtained for naftopidil (2.53, 1.81 - 3.53), silodosin (4.24, 2.37 - 5.20), and tamsulosin (2.22, 1.75 - 2.81). The median onset times of syncope for naftopidil, silodosin, and tamsulosin were 37, 26, and 108 days, respectively. The shape parameters obtained by fitting the data for the three α1Bs to the Weibull distribution were all less than 1.0, indicating that all these drugs could be classified as the early failure type. The cumulative incidence rates showed that the onset times of syncope tended to be similar among the three α1Bs. Conclusions: Patients treated with selective α1Bs should be closely monitored for 100 days, especially in the first 20 to 40 days after initiation of silodosin or naftopidil. This information may be useful for patients and healthcare professionals in preventing syncope due to the use of selective α1Bs.
背景:α1-肾上腺素受体阻滞剂(α 1b)被用于治疗良性前列腺增生和高血压,但已知它们会引起低血压相关的不良事件。本研究的目的是评估与α 1b使用相关的晕厥发病时间概况。方法:分析2004年4月至2016年11月日本不良药物事件报告(JADER)数据库中的数据,采用歧化分析方法计算日本市场上8种α 1b的报告优势比(RORs)。此外,还分析了记录在JADER数据库中的时间信息,以评估不良事件的发生时间。结果:共分析了186,724例20岁以上男性的报告。naftopidil(2.53, 1.81 - 3.53)、silodosin(4.24, 2.37 - 5.20)和tamsulosin(2.22, 1.75 - 2.81)对晕厥有显著的RORs(95%可信区间)。纳托地尔、西洛多辛和坦索罗辛的中位晕厥发作时间分别为37、26和108天。3种α 1b药物的数据拟合Weibull分布得到的形状参数均小于1.0,说明这3种药物均可归为早期失效型。累积发病率显示,3个α 1b组的晕厥发作次数趋于相似。结论:选择性α 1b治疗的患者应密切监测100天,特别是西洛多辛或纳托地尔开始治疗后的前20 ~ 40天。这一信息可能对患者和医疗保健专业人员预防选择性α 1b引起的晕厥有用。
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引用次数: 1
Antidepressant-Like Activity of Methanolic Extract of the Seeds of Trachysperum ammi in Swiss Albino Mice 羊草种子甲醇提取物对瑞士白化病小鼠的抗抑郁活性
Pub Date : 2018-12-07 DOI: 10.4236/PP.2018.912039
Md Rashidur Rahman, Mohammad Ali, Mostakim Sharif, S. Sajon, M. Mannan, Md. Shahed-Al-Mahmud
Trachysperum ammi has been traditionally used for the treatment of neurological disorders such as depression and anxiety. To date, T. ammi has reported for its chemical constituents in different diseases condition. The traditional evidence convinced us to perform the antidepressant-like activity of methanolic extract of Trachysperum ammi (META). The antidepressant activity of META assessed by using forced swimming test (FST), tail suspension test (TST), and locomotor activity test. The seed parts of META at doses level of 50, 100 and 200 mg/kg body weight administered orally to examine the CNS stimulants activity test in mice behavioral models. Here, we reported that META significantly reduced immobility time in the FST after repeated administration of 50, 100 and 200 mg/kg to mice for 14 days. The intensity of immobility significantly reduced at all of the doses (p < 0.05) whereas, we were found the strongest effect observed at 200 mg/kg. The antidepressant-like effect of META caused the reduction (p < 0.05) in the immobility in TST of mice when orally administered with 50, 100 and 200 mg/kg for 14 days, respectively. Additionally, we were executed locomotor activity test to check the motor stimulating activity. META has employed at a dosage of 50, 100 and 200 mg/kg for 14 days, the results have found that 50 mg/kg produced the locomotion effects as similar to the control group. Interestingly, the locomotion, rearing, and defecation significantly (p < 0.05) increased at the dosage of 100 and 200 mg/kg of META. Our present findings suggest that the seed parts of Trachysperum ammi may possess antidepressant-like activity which may use as a supportive treatment to management of neurological disorders.
羊草传统上被用于治疗神经系统疾病,如抑郁症和焦虑症。迄今为止,已报道了其化学成分在不同疾病条件下的作用。传统的证据使我们确信草精(META)的甲醇提取物具有类似抗抑郁的活性。采用强迫游泳试验(FST)、悬尾试验(TST)和运动活动试验评估META的抗抑郁活性。以50、100、200 mg/kg体重剂量口服META种子部分,观察其对小鼠行为模型中枢神经系统兴奋剂活性的影响。在这里,我们报道了在给小鼠重复给药50、100和200 mg/kg后14天,META显著减少了FST中的静止时间。在所有剂量下,静止的强度都显著降低(p < 0.05),而在200 mg/kg时,我们发现效果最强。META具有抗抑郁样作用,分别以50、100和200 mg/kg口服14 d时,小鼠TST的不动性降低(p < 0.05)。此外,我们进行了运动活动测试,以检查运动刺激活动。META以50mg /kg、100mg /kg和200mg /kg的剂量连续使用14天,结果发现50mg /kg组的运动效果与对照组相似。有趣的是,100和200 mg/kg添加量显著提高了运动、饲养和排便(p < 0.05)。我们目前的研究结果表明,鼠叶草种子部分可能具有抗抑郁活性,可能用作神经系统疾病管理的支持治疗。
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引用次数: 1
Surprising Separation of Cannabinoid Physical Dependence and Withdrawal in an Invertebrate Model 在无脊椎动物模型中大麻素物理依赖和戒断的惊人分离
Pub Date : 2018-12-07 DOI: 10.4236/PP.2018.912038
Wanhui Sheng, R. Raffa
Planarians have mammalian-like neurotransmitter systems and have been established as a novel in vivo model for neuropharmacology. In previous research, planarians that have been exposed to the cannabinoid receptor (CB-R) agonist WIN 55,212-2 for 1 h displayed abstinence-induced withdrawal when tested in drug-free, but not in drug-containing, water. The goals of the present study were to extend previous work and to further establish a cannabinoid behavioral model with planarians. The results showed 1) four different CB-R antagonists (AM251, AM281, SLV319 and SR144528) dose-relatedly blocked development of physical dependence induced by two different CB-R agonists (WIN 55,212-2 and JWH251); 2) none of the same four antagonists (AM251, AM281, SLV319 or SR144528) precipitated withdrawal; 3) short wavelength (254 nm), but not long wavelength (366 nm), ultraviolet (UV) light attenuated abstinence-induced withdrawal from WIN 55,212-2, while short wavelength UV light induced moderate withdrawal behavior. The results confirm the use of a planarian model as a simple yet robust way to study development of physical dependence to cannabinoid agonists. The effect of UV irradiation adds to the evidence that the results are receptor-related. The results also give rise to the surprising suggestion, within the limitations of the methodology, that development of cannabinoid physical dependence and antagonist-induced precipitated withdrawal might be separable phenomena in planarians.
纯肠动物具有类似哺乳动物的神经递质系统,已被建立为一种新的体内神经药理学模型。在先前的研究中,暴露于大麻素受体(CB-R)激动剂WIN 55,212-2 1小时的涡虫在无药水中表现出戒断诱导的戒断,而在含药水中则没有。本研究的目的是扩展先前的工作,并进一步建立大麻素与涡虫的行为模型。结果表明:1)4种不同的CB-R拮抗剂(AM251、AM281、SLV319和SR144528)对2种不同CB-R拮抗剂(WIN 55,212-2和JWH251)诱导的身体依赖具有剂量相关阻断作用;2)相同的四种拮抗剂(AM251、AM281、SLV319或SR144528)均未引起停药;3)短波长紫外光(254 nm)可减弱戒断诱导的WIN 55,212-2戒断行为,而短波长紫外光(366 nm)可诱导中度戒断行为。结果证实使用涡虫模型作为一种简单而有力的方法来研究对大麻素激动剂的身体依赖的发展。紫外线照射的影响进一步证明了这一结果与受体有关。结果还提出了令人惊讶的建议,在方法的限制下,大麻素身体依赖的发展和拮抗剂诱导的沉淀戒断可能是涡虫中可分离的现象。
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Pharmacology & Pharmacy
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