盐酸安非他酮缓释片稳定性的研究

目的：研究盐酸安非他酮缓释片的稳定性。方法；经空气、光照、高温，高湿，加速，室温条件放置，测定其稳定性，结果：本品经各种试验条件的影响，其外观均为白色薄膜衣片，除去薄膜衣显类白色，释放度，含量、有关物质等各项考察指标与放置前比较均无明显变化。结论：本品具有较好的稳定性。     

安非他酮联用碳酸锂缓释片治疗双相抑郁的对照研究

目的:探讨安非他酮联用碳酸锂缓释片治疗双相抑郁的疗效及安全性。方法:进行8周开放式前瞻性随机对照研究,将78例符合《精神疾病诊断与统计手册》第4版(DSM-IV)双相抑郁诊断标准的住院患者随机分成观察组(安非他酮联用碳酸锂缓释片治疗,n=40)及对照组(单用碳酸锂缓释片治疗,n=38),分别在基线及1、2、4、8周末应用汉密尔顿抑郁量表(HAMD-17)评定疗效,同时应用Bech-Rafaelsen躁狂量表(BRMS)评定转躁情况,用治疗中出现的症状量表(TESS)及实验室检查评定不良反应。结果:8周末两组HAMD总分(8±3,8±4)与基线(24±7,25±8)相比均明显降低(P<0.01),两组间HAMD总分比较差异无统计学意义(P>0.05)。第1、2周末观察组的HAMD总分(21±7,12±5)分别低于对照组(25±8,16±6)(P<0.05)。同时观察组第2周末的有效率(30%)及治愈率(20%)亦明显高于对照组的10.5%、2.6%(P<0.05)。第4、8周末时观察组HAMD总分分别为9±4、8±3,与对照组(9±5,8±4)比较无统计学差异(P>0.05),同时第8周末两组有效率(90%vs89.5%)及治愈率(62.5%vs60.5%)比较亦无统计学差异(P>0.05)。两组间不良反应类似,研究过程中两组均无病例转躁。结论:安非他酮联用碳酸锂缓释片及单用碳酸锂缓释片治疗双相抑郁均安全有效,安非他酮联用碳酸锂缓释片治疗双相抑郁可加快起效速度,同时并不增加转躁风险。     

盐酸安非他酮缓释片戒除烟瘾的初步临床试验

目的:初步评价国产盐酸安非他酮缓释片戒除烟瘾的有效性及安全性。方法:采用随机、双盲、安慰剂平行对照研究。受试者随机分为2组,分别口服盐酸安非他酮缓释片150-300 mg.d-1或安慰剂,疗程4周,观察12周。结果:共入组自愿戒烟者48例,其中盐酸安非他酮组24例,安慰剂组24例。自治疗后1周起,盐酸安非他酮组日吸烟量的减少值均大于安慰剂组(P<0.01)。治疗后4周盐酸安非他酮组戒烟率为29.2%,高于安慰剂组(P<0.05)。盐酸安非他酮组常见的不良反应为:困倦、口干、注意力不集中、腹部不适和乏力。结论:国产盐酸安非他酮缓释片是一种安全有效的戒烟药物,不良反应轻。     

盐酸安非他酮缓释片治疗抑郁症的临床试验

目的:评价国产盐酸安非他酮缓释片治疗抑郁症的有效性和安全性。方法:采用随机、双盲、双模拟、阳性药平行对照研究。48例抑郁症患者随机分为试验组24例与对照组24例,分别口服盐酸安非他酮缓释片300mg·d~(-1)或氟西汀20mg·d~(-1),疗程42d,观察汉密尔顿抑郁量表与临床总体印象量表总分变化及药物不良反应等。结果:两组汉密尔顿抑郁量表评分在治疗结束时较基线均显著减少(P＜0．01);试验组与对照组有效率分别为86．4%与73．9%,差异无显著性(P＞0．05)。试验组常见的不良反应为:恶心呕吐、头昏、口干、食欲减退。结论:盐酸安非他酮缓释片治疗抑郁症安全而有效。     

口服治疗肥胖药物——纳曲酮/安非他酮缓释片

纳曲酮/安非他酮缓释片(naltrexone-bupropion,Contrave)缓释片是由Orexigen Therapeutic公司研发的肥胖治疗药物,它由纳曲酮与安非他酮组成,在2014年9月10日经FDA批准上市。纳曲酮/安非他酮缓释片用于治疗体质指数为30或更大(肥胖)的成人患者,以及体质指数为27或更大(超重)并且患有至少一种体重相关疾病的成人患者,如高血压、2型糖尿病或血脂异常。同时纳曲酮/安非他酮缓释片作为一种结合低热量饮食及体育锻炼治疗肥胖的辅助药物。笔者就纳曲酮/安非他酮缓释片的基本信息、作用机理、药代动力学、药物相互作用、临床研究、药物不良反应以及药物过量、安全警告和警示等研发动态作一概述,以期为医院临床用药起到指导作用。     

盐酸安非他酮缓释片人体药代动力学研究

目的:研究国产盐酸安非他酮缓释片在中国健康人体内的药代动力学特征.方法:19名健康男性志愿者单剂量口服300mg盐酸安非他酮缓释片,采用HPLC法测定血浆中盐酸安非他酮浓度,并用3P97软件统计处理.结果:盐酸安非他酮供试缓释片药-时曲线符合二室模型,其Cmax为(221.08±64.42)μg·L-1;tmax为(2.95±0.78)h,t1/2为(16.78±5.26)h;AUC0-48为(1758.4±323.7)μg·L-1·h;AUC0-∞为(1969.2±351.4)μg·L-1·h.结论:为临床合理用药提供了参考资料.     

安非他酮应用于抑郁症和戒除烟瘾

目的:对安非他酮的作用机制和临床应用现状进行介绍,以供临床用药参考。方法:查阅国内外相关文献,进行评价。结果及结论:安非他酮作为一种5-羟色胺和多巴胺再摄取的双重抑制剂,不仅可以用于抑郁症的治疗,对于戒除烟瘾也有一定的疗效。常见不良反应为口干、头痛、恶心、失眠等。     

盐酸安非他酮缓释片治疗焦虑症的临床观察

目的观察盐酸安非他酮缓释片用于焦虑症临床治疗的疗效及不良反应,探讨安非他酮作为新型抗焦虑药物的应用价值。方法选取59例焦虑症患者,按照分段随机法分为安非他酮组(治疗组)30例及氟西汀组(对照组)29例,两组患者分别口服安非他酮片300mg/d及氟西汀片20mg/d,疗程均为6周。分别于治疗前后采用汉密尔顿焦虑量表(HAMA)及临床总体印象量表(CGI)评价两组疗效,并进行统计学分析及安全性分析。结果疗程结束后,治疗组及对照组的临床有效率分别为66.7%、65.6%(P>0.05),HAMA减分值分别为(8.80±5.59)、(8.79±5.31)(P>0.05),临床总体印象降低值分别为(2.60±0.86)、(2.93±1.03)(P>0.05),不良事件发生率分别为63.3%,48.3%(P>0.05),未发生严重不良事件,各项指标差异均无统计学意义。结论盐酸安非他酮用于焦虑症的治疗具有与氟西汀相近的疗效及安全性,可作为一种新型抗焦虑药物用于临床治疗。     

HPLC法测定盐酸安非他酮缓释片的释放度

目的:建立测定盐酸安非他酮缓释片释放度的方法.方法:采用HPLC法,色谱柱为Kromasil C18(150 mm×4.6 mm,5μn);流动相为磷酸盐缓冲液(pH 5.8)-乙腈(60:40),检测波长251 nm.结果:线性范围为0.061～0.548μg(r=1.000 0),平均回收率为100.3%,RSD%=0.18%(n=9).结论:所用方法简便、快速,专属性强,灵敏度高,准确性好.     

A Workshop on Smoking Cessation for Pharmacy Students

Objective. To develop, implement, and evaluate a targeted educational intervention focusing on smoking cessation with final-year undergraduate pharmacy students.Design. A smoking-cessation educational workshop entitled Smoking Cessation in Pharmacy (SCIP) was designed on the principles of adult learning and implemented with a full cohort of final-year undergraduate pharmacy students at the University of Sydney. A previously validated questionnaire testing the knowledge and attitudes of respondents was administered both before and after implementation of the designed workshop to evaluate changes resulting from the intervention. Informal feedback was obtained from students.Assessment. Pre-course mean total knowledge and attitude scores calculated were 65.8±9.1 and 86.4±12.1, respectively. The post-course mean total knowledge score was 74.9±8.1, and the attitude score was 88.8±9.1 Improvement in knowledge and attitudes was significant (p<0.05).Conclusion. Educational interventions for pharmacy students designed with careful attention to pedagogic principles can improve knowledge about evidence-based smoking-cessation strategies and enhance positive attitudes to pharmacist roles in smoking cessation.     

Current and Emerging Pharmacotherapies for Cessation of Tobacco Smoking

Tobacco use disorder is a chronic illness. With its high comorbidity rate, it is a major cause of years of life lost or years lived with disability; however, it is also considered the most preventable cause of death in developed countries. Since the development of nicotine replacement therapy (NRT) in 1978, treatment options have continued to evolve and expand. Despite this, currently available treatments remain insufficient, with less than 25% of smokers remaining abstinent 1 year after treatment. In this article, we review existing and emerging smoking cessation pharmacotherapies, with a special emphasis on the most promising agents that are currently being investigated. A search of the Cochrane Database of Systematic Reviews and the PubMed, Ovid, and ClinicalTrials.gov databases (August 2 to September 1, 2017) was undertaken for articles on smoking cessation pharmacotherapies, applying no language restrictions. More than 40 pharmacotherapies were reviewed including conventional pharmacotherapies—NRT, bupropion, and varenicline (all approved by the U.S. Food and Drug Administration as first‐line treatment of smoking cessation)—and novel therapies: cytisine, N‐acetylcysteine, cycloserine, memantine, baclofen, topiramate, galantamine, and bromocriptine. Studies of combination NRT and varenicline showed the greatest smoking cessation rates. Clonidine and nortriptyline are second‐line treatments used when first‐line treatments fail or are contraindicated, or by patient preference. Some novel therapies, especially acetylcholinesterase inhibitors, cytisine, and N‐acetylcysteine, display promising results. Because the results of randomized clinical trials were reported using varied end points and outcome measures, direct comparisons between different pharmacotherapies cannot easily be evaluated. Additional high‐quality randomized double‐blind placebo‐controlled trials with long‐term follow‐up, using validated sustained abstinence measures, are needed to find more effective smoking cessation aids.     

Distress Tolerance and Perceived Barriers to Smoking Cessation

ABSTRACT. Background: The present study examined the role of emotional distress tolerance (DT) in predicting barriers to smoking cessation and number of quit attempts. Methods: The sample consisted of regular daily smokers (N = 126; 37 females; M _age = 36.51, SD = 13.05) who completed self-report measures on affect and smoking. Results: After controlling for daily smoking rate and anxiety sensitivity, emotional DT significantly predicted internal barriers to cessation (6.9% unique variance) but not external or addiction-related barriers to cessation. Inconsistent with prediction, emotional DT did not significantly predict number of quit attempts. Conclusions: These results suggest that individuals who are low in emotional DT believe that quitting smoking will be difficult because it takes away an important affect regulation strategy, and there may be utility in targeting emotional DT in smoking cessation interventions.     

Adolescent Attributes and Young Adult Smoking Cessation Behavior

This study collected data five times between 1983 and 2002 from 400 participants who originally came from upstate New York. These participants completed structured interviews as did their mothers three times. LISREL analysis generally supported the hypothesized model. The results indicated that having parents who smoked and having low educational aspirations and expectations were associated with being unconventional, which, in turn, was related to having low emotional control and reporting more internalizing behaviors. Internalizing behaviors were directly associated with a lower likelihood of smoking cessation, as was parental smoking. Research and clinical implications are discussed and the limitations noted.     

Racial and Ethnic Differences in Predictors of Smoking Cessation

Racial/ethnic differences in the determinants of smoking cessation could have important treatment implications. The current study examined racial/ethnic differences in smoking cessation, prospective predictors of cessation, and whether the predictive ability of these factors differed by race/ethnicity. Participants were 709 employed adults recruited through the National Rural Electric Co-op Association or through natural gas pipeline corporations. Data were collected in 1990 and 1994. Although race/ethnicity was not predictive of abstinence, Hispanic, African American, and White smokers displayed differential on tobacco-, alcohol-, and work-related variables. These racial/ethnic differences highlight the specific factors that should be considered when providing smoking cessation treatment to specific populations. Limitations are noted.     

Smoking Cessation Pharmacogenetics: Analysis of Varenicline and Bupropion in Placebo-Controlled Clinical Trials

Despite effective therapies for smoking cessation, most smokers find quitting difficult and most successful quitters relapse. Considerable evidence supports a genetic risk for nicotine dependence; however, less is known about the pharmacogenetics of smoking cessation. In the first pharmacogenetic investigation of the efficacy of varenicline and bupropion, we examined whether genes important in the pharmacodynamics and pharmacokinetics of these drugs and nicotine predict medication efficacy and adverse events. Subjects participated in randomized, double-blind, placebo-controlled smoking cessation clinical trials, comparing varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist, with bupropion, a norepinephrine/dopamine reuptake inhibitor, and placebo. Primary analysis included 1175 smokers of European ancestry, and 785 single nucleotide polymorphisms from 24 genes, representing 254 linkage disequilibrium (LD) bins (genes included nAChR subunits, additional varenicline-specific genes, and genes involved in nicotine or bupropion metabolism). For varenicline, continuous abstinence (weeks 9–12) was associated with multiple nAChR subunit genes (including CHRNB2, CHRNA5, and CHRNA4) (OR=1.76; 95% CI: 1.23–2.52) (p<0.005); for bupropion, abstinence was associated with CYP2B6 (OR=1.78; 95% CI: 1.27–2.50) (p<0.001). Incidence of nausea was associated with several nAChR subunit genes (OR=0.50; 95% CI: 0.36–0.70) (p<0.0001) and time to relapse after quitting was associated with HTR3B (HR=1.97; 95% CI: 1.45–2.68) (p<0.0001). These data provide evidence for multiple genetic loci contributing to smoking cessation and therapeutic response. Different loci are associated with varenicline vs bupropion response, suggesting that additional research may identify clinically useful markers to guide treatment decisions.     

Better Late Than Never: The Perceived Benefits of Smoking Cessation Among Women in Late Midlife

The current study examined the association of smoking cessation (≥1 year without relapse) and self-reported psychosocial and physical outcomes among a community sample of women (N = 195; mean age = 63.7 years, SD = 5.7 years). Data were collected in 1985–1986 and 2009. Successful smoking cessation for ≥1 year was significantly associated with each of the outcome measures (e.g., less financial stress [adjusted odds ratio (AOR) = 0.50; 95% confidence interval (CI) = 0.25–1.00, P< 0.05), less life dissatisfaction (AOR = 0.51, 95% CI = 0.24–1.09, P< 0.05). Findings suggest that older women should be included in smoking cessation programs, and the important benefits of quitting should be used to encourage cessation.     

Common and Unique Biological Pathways Associated with Smoking Initiation/Progression, Nicotine Dependence, and Smoking Cessation

Twin and family studies reveal a significant genetic contribution to the risk of smoking initiation and progression (SI/P), nicotine dependence (ND), and smoking cessation (SC). Further, numerous genes have been implicated in these smoking-related behaviors, especially for ND. However, no study has presented a comprehensive and systematic view of the genetic factors associated with these important smoking-related phenotypes. By reviewing the literature on these behaviors, we identified 16, 99, and 75 genes that have been associated with SI/P, ND, and SC, respectively. We then determined whether these genes were enriched in pathways important in the neuronal and brain functions underlying addiction. We identified 9, 21, and 13 pathways enriched in the genes associated with SI/P, ND, and SC, respectively. Among these pathways, four were common to all of the three phenotypes, that is, calcium signaling, cAMP-mediated signaling, dopamine receptor signaling, and G-protein-coupled receptor signaling. Further, we found that serotonin receptor signaling and tryptophan metabolism pathways were shared by SI/P and ND, tight junction signaling pathway was shared by SI/P and SC, and gap junction, neurotrophin/TRK signaling, synaptic long-term potentiation, and tyrosine metabolism were shared between ND and SC. Together, these findings show significant genetic overlap among these three related phenotypes. Although identification of susceptibility genes for smoking-related behaviors is still in an early stage, the approach used in this study has the potential to overcome the hurdles caused by factors such as genetic heterogeneity and small sample size, and thus should yield greater insights into the genetic mechanisms underlying these complex phenotypes.