2008年第1季度门诊不合理抗菌药物处方点评

目的开展门诊抗菌药物处方点评，促进医院合理用药。方法随机抽查四川省内江市第二人民医院2008年1～3月的门诊处方3000张，对不合格处方进行统计、点评。结果3000张被抽查处方中应用抗菌药物的处方有840张（占28．0％），其中不合理处方189张，不合格率为22．5％，占所抽查处方的6．3％，主要表现在抗菌药物超范围使用、联合用药不正确、用药档次高等。结论应加强门诊抗菌药物处方的审核力度，提高医院特殊管理抗菌药物的合理用药水平     

我院皮肤科门诊抗菌药物不合理应用分析

目的：分析医院皮肤科门诊抗菌药物不合理用药原因,为进一步规范本院抗菌药物的使用管理提供参考。方法：随机抽取我院2008年度每月11—20日皮肤科门诊处方（18岁以上患者）共计19905张,对使用抗菌药物处方的抗菌药物DDDs、DUI、处方的诊断与用药相符性、联合用药不合理性及单张处方不合理项进行统计分析。结果：使用抗菌药物处方为5034张,占总抽查处方的25．29％。其中,不合理处方1449张,占使用抗菌药物处方的28．78％。结论：医院门诊抗菌药物不合理应用情况表现形式多样,应加强干预和管理。     

门诊抗菌药物不合理应用分析

目的：通过对本院2011年1—6月门诊处方抗菌药物的应用分析,了解不合理用药情况,提高门诊医生用药水平。方法：抽查门诊西药房2011年1—6月全部处方,对抗菌药物不合理应用情况进行回顾性分析。结果：共抽查处方43200张,其中使用抗菌药物处方11547张,占26．73％;不合理处方878张,占7．6％,主要表现在用药指征不明、配伍不合理、给药方法不当、剂量不正确、用药档次偏高等方面。结论：本院门诊抗菌药物使用基本合理,但与卫生部抗菌药物专项整治活动要求有一定差距,有待进一步提高。     

我院门诊抗菌药物应用监测实践与干预

目的 掌握门诊抗菌药物应用动态,促进合理用药。方法 通过对门诊处方定期随机抽查,结合我国卫生部规定的抗生素使用率,对不合理应用抗菌药物的处方进行分析和干预。结果2007年1月至12月共抽查处方77923张,其中抗菌药物处方有45306张（占58．14％）。实行第1次干预方案后,2008年1月至7月抽查处方54266张,其中抗菌药物处方30287张（占55．81％）;实行第2次干预方案后．2008年7月至10月共查处方22661张,其中抗菌药物处方11400张（占50．31％）;实行第3次干预方案后,联合用药以一联为主,二联为辅。三联、四联明显减少。结论实行干预方案后,抗菌药物合理使用率明显提高。     

濮阳市油田总医院门诊抗菌药物应用分析

目的：了解我院门诊抗菌药物使用情况,并按卫生部标准时其合理性进行评价,为临床用药提供参考。方法：逐月抽查2011年我院门诊处方共13888张,统计抗菌药物的使用情况,并对其使用合理性进行评价。结果：2011年我院累计抽查13888张门诊处方,使用抗茵药物的处方有3222张,抗菌药物使用率为23．20％。使用的抗菌药物共9大类39个品种66个规格,主要以头孢菌素类为主,其次为大环内酯类和氟喹诺酮类。销售金额排序前10位抗菌药物的销售金额为404．78万元．占抗菌药物总销售金额的65．94％（404．78／613．82）。不合理使用抗菌药物处方有237张,占使用抗茵药物处方的7．36％（237／3222）,占不合理用药处方总数的63．88％（237／371）。结论：我院门诊处方抗菌药物使用基本合理,但也存在抗菌药物选用较为集中、起点较高等问题,应继续加强用药监管。     

2004年1～6月门诊抗菌药物使用的调查分析

目的：了解本院门诊抗菌药物的使用情况，以便更好地合理应用抗菌药物。方法：随机抽查统计分析本院2004年1娟月门诊处方11175张。结果：11175张处方中使用抗菌药物有8103张，占处方总数的72．51％。其中口服抗菌药物占33．95％；注射用抗菌药物占51．67％；外用抗菌药物占10．75％；2种抗菌药物联用的有702张，占抗菌药物处方数的8．66％；3种抗菌药物联用的有78张，占抗菌药物处方数的0．96％。结论：定期统计分析本院门诊抗菌药物的使用情况，可进一步了解其使用抗菌药物是否合理、安全．有效。     

2013年息烽县人民医院门诊抗菌药物处方分析

目的 调查分析2013年息烽县人民医院门诊处方抗菌药物合理使用情况.方法 对息烽县人民医院2013年门诊处方采用HS系统统计,并随机抽取抗菌药物应用处方,对其品种、使用频率、联合用药、存在的不合理问题等情况进行分析.结果 共抽取息烽县人民医院门诊处方138859张,其中抗菌药物处方25058张,占总处方的18.05％.抽查的2646张抗菌药物处方中使用注射剂抗菌药物的处方1385张,占抽查抗菌药物处方的53.24％;口服抗菌药物处方1261张,占抽查抗菌药物处方的46.76％;二联及二联以上抗菌药物处方56张,占抽查抗菌药物处方的2.12％.罗红霉素胶囊应用频率最高,占16.44％.儿科应用抗菌药物频次较高,占49.44％.结论 息烽县人民医院门诊抗菌药物使用基本合理,但也存在一些不足,需加强对医务人员合理应用抗菌药物的培训.     

我院门诊杭菌药物处方点评与分析

目的提高医疗质量,促进合理使用抗菌药物。方法随机抽查医院2012年7月至12月门诊处方12000张,对抗菌药物不合理应用情况进行回顾性分析。结果门诊抗茵药物的使用率为26．80％,其中不合理使用抗菌药物处方256张,占抗菌药物处方的7．96％。结论医院门诊抗菌药物的使用率偏高且存在不合理使用,应加强用药监督和指导。     

儿科门诊抗菌药物不合理处方分析

为了减少药源性疾病的发生，指导医生正确选择和应用药物治疗，确保病人用药安全和合理，我们进行了儿科门诊抗菌用药情况调查，现报道如下。1一般资料1．1资料来源本次调查是抽查我院儿科1998年1月～6月共6个月的门诊处方4960张，采取随机抽取法共取1000张，其中含有抗菌药物处方958张（95．8％），其中不合理抗菌药物处方63张，占抗菌用药处方的6．58％。1．2结果本次所抽查的不合理抗菌药物处方共63张，主要表现在联合用药的不合理、用法不当及抗菌药与婴幼儿的相互影响三个方面。其中两种药物合用后产生相互作用的处方sl张，包括作用于…     

门诊抗菌药物处方调查分析

目的调查分析医院门诊抗菌药物使用情况,促进抗菌药物的合理应用。方法随机抽查8700张门诊处方,其中抗菌药物处方2138张,并依据《抗菌药物临床应用指导原则》等相关文献资料,对不合理的抗菌药物处方进行归类统计分析。结果抽查的抗菌药物处方中,不合理处方298张(占13.94%),其中皮试要求不明确不合理处方26张(占1.22%),用法用量不合理处方78张(占3.65%),用药频次不合理处方52张(占2.43%),重复用药不合理处方43张(占2.01%),配伍不合理处方99张(占4.63%)。结论门诊抗菌药物的不合理使用现象普遍存在,其处方管理和规范合理使用的意识亟待加强,以提高抗菌药物的疗效,最大限度地减少其毒副作用和耐药性的产生。     

鹿瓜多肽注射制剂致过敏性休克39例分析

目的探讨鹿瓜多肽注射液致过敏性休克的特点与规律,为临床合理用药提供参考。方法在线检索国内有关医药数据库,下载病例报告原文,统计患者年龄、性别、原患疾病、药物和食物过敏史、给药途径与剂量、发生过敏性休克的时间及临床表现与转归等。结果共检索到鹿瓜多肽注射液致过敏性休克39例。其致过敏性休克的特点与规律是：男性患者占比较高（25例,占64．10％）,20～60岁患者占比较高（34例,占87．18％）,静脉滴注给药者占比较高（38例,97．44％）,首次用药占比较高（36例,占92．31％）,静滴开始后30min内发生者占比较高（35例,占89．74％）,过敏性休克的临床症状以呼吸系统（呼吸困难、胸闷）和心血管系统（血压骤降、大汗淋漓）为主。结论鹿瓜多肽注射液引起过敏性休克与性别、原患疾病和给药途径等有关,临床用药须重视过敏史询问、用药过程中不良反应的观察,以及为应对可能出现的过敏性休克先兆症状积极做好抢救准备。     

Natural products as promising drug candidates for the treatment of hepatitis B and C

Hepatitis B virus （HBV） or hepatitis C virus （HCV） infections are a major threat worldwide. Combination therapy of interferon-α and ribavirin is currently the treatment of choice for HCV-infected patients. However, this regimen is only effective in approximately 50% of patients and provokes severe side-effects. Numerous natural alternatives for treating HCV have been suggested. Deoxynojirimycin and its derivatives are iminosugars which exert anti-HCV activity by inhibiting α-glucosidases. A non-immunosuppressive derivate of cyclosporine A, NIM811, exerts anti-HCV activity by binding to cyclophilin. Other natural products with promising anti-HCV activity are 2-arylbenzofuran derivatives, Mellein, and pseudoguaianolides. For HBV treatment, several drugs are available, specifically targeting the virus polymerase （lamivudine, entecavir, telbivudine, and adefovir dipivoxil）. The efficacy of these drugs is hampered by the development of resistance due to point mutations in the HBV polymerase. Due to drug resistance and adverse side-effects, the search for novel drugs is mandatory. Wogonin, ellagic acid, artemisinin and artesunate, chrysophanol 8-O-β-D-glucoside, saikosaponin C, and protostane triterpenes are active against HBV. Natural products need to be investigated in more detail to explore their potential as novel adjuncts to established HBV or HCV therapy.     

Composite glycidyl methacrylated dextran （Dex-GMA）/gelatin nanoparticles for localized protein delivery

Aim： Localized delivery of growth factors has significant potential as a future therapeutic strategy in tissue engineering and regenerative medicine. A nanoparticle vehicle was created and evaluated in this study with the intent to deliver growth factors for periodontal regeneration.
Methods： Novel composite nanoparticles based on glycidyl methacrylate derivatized dextrans （Dex-GMA） and gelatin were fabricated by a facile method without using any organic solvents. The configurations of the resultant nanoparticles were evaluated by transmission electron microscopy, scanning electron microscopy, and atomic force microscope. Their surfaces were characterized by zeta-potential measurements, after which their properties including swelling, degradation, drug release, and cytotoxicity were also investigated using in vitro models. Results： The particle size of Dex-GMA/gelatin nanoparticles （DG-NPs） ranged from 20 to 100 nm and showed a mono-dis- perse size distribution （mean diameter 53.7 nm） and a strongly negative surface zeta potential （-20 mV）. The DG-NPs were characterized by good swelling and degradation properties in media including dextranase. The in vitro drug release studies showed that the efficient bone morphogenetic protein （BMP） release from DG-NPs was maintained for more than 12 d under degradation conditions, where more than 90% of the loaded BMP was released. No any relevant cell damage caused by DG-NPs was found in the cytotoxicity tests for a period of 24 h.
Conclusion： These combined results demonstrate that DG-NPs fulfill the basic prerequisites for growth factor delivery. With further in vivo studies, those nanoparticles may offer a promising vehicle for the delivery of active drugs to the perio- dontium.     

The expression of efflux and uptake transporters are regulated by statins in Caco-2 and HepG2 cells

Aim： Statin disposition and response are greatly determined by the activities of drug metabolizing enzymes and efflux/uptake transporters. There is little information on the regulation of these proteins in human cells after statin therapy. In this study, the effects of atorvastatin and simvastatin on mRNA expression of efflux （ABCB1, ABCG2 and ABCC2） and uptake （SLCO1B1, SLCO2B1 and SLC22A1） drug transporters in Caco-2 and HepG2 cells were investigated.
Methods： Quantitative real-time PCR was used to measure mRNA levels after exposure of HepG2 and Caco-2 cells to statins. Results： Differences in mRNA basal levels of the transporters were as follows： ABCC2〉ABCG2〉ABCB1〉SLCO1B1〉〉〉SLC22A1〉SLCO2B1 for HepG2 ceils, and SLCO2B1〉〉ABCC2〉ABCB1〉ABCG2〉〉〉SLC22A1 for Caco-2 cells. While for HepG2 cells, ABCC2, ABOG2 and SLCO2B1 mRNA levels were significantly up-regulated at 1, 10 and 20 pmol/L after 12 or 24 h treatment, in Caco-2 cells, only the efflux transporter ABCB1 was significantly down-regulated by two-fold following a 12 h treatment with atorvastatin. Interestingly, whereas treatment with simvastatin had no effect on mRNA levels of the transporters in HepG2 cells, in Caco-2 cells the statin significantly down-regulated ABCB1, ABCC2, SLC22A1, and SLCO2B1 mRNA levels after 12 or 24 h treatment.
Conclusion： These findings reveal that statins exhibits differential effects on mRNA expression of drug transporters, and this effect depends on the cell type. Furthermore, alterations in the expression levels of drug transporters in the liver and/or intestine may con- tribute to the variability in oral disposition of statins.     

Addictive evaluation of cholic acid-verticinone ester,a potential cough therapeutic agent with agonist action of opioid receptor

Aim： The purpose of this work was to search for potential drugs with potent antitussive and expectorant activities as well as a low toxicity, but without addictive properties. Cholic acid-verticinone ester （CA-Ver） was synthesized based on the clearly elucidated antitussive and expectorant activities of verticinone in bulbs of Fritillaria and different bile acids in Snake Bile. In our previous study, CA-Ver showed a much more potent activity than codeine phosphate. This study was carried out to investigate the central antitussive mechanism and the addictive evaluation of CA-Ver. Methods： Testing on a capsaicin-induced cough model of mice pretreated with naloxone, a non-selective opioid receptor antagonist, was performed for the observation of CA-Ver＇s central antitussive mechanism. We then took naloxone-induced withdrawal tests of mice for the judgment of CA-Ver＇s addiction. Lastly, we determined the opioid dependence of CA-Ver in the guinea pig ileum. Results： The test on the capsaicin-induced cough model showed that naloxone could block the antitussive effect of CA-Ver, suggesting the antitussive mechanism of CA-Ver was related to the central opioid receptors. The naloxone-urged withdrawal tests of the mice showed that CA-Ver was not addictive, and the test of the opioid dependence in the guinea pig ileum showed that CA-Ver had no withdrawal response. Conclusion： These findings suggested that CA-Ver deserved attention for its potent antitussive effects related to the central opioid receptors, but without addiction, and had a good development perspective.     

Allosteric activation mechanism of the cys-loop receptors

Binding of a neurotransmitter to its ionotropic receptor opens a distantly located ion channel, a process termed allosteric activation. Here we review recent advances in the molecular mechanism by which the cys-loop receptors are activated with emphasis on the best studied nicotinic acetylcholine receptors （nAChRs）. With a combination of affinity labeling, mutagenesis, electrophysiology, kinetic modeling, electron microscopy （EM）, and crystal structure analysis, the allosteric activation mechanism is emerging. Specifically, the binding domain and gating domain are interconnected by an allosteric activation network. Agonist binding induces conformational changes, resulting in the rotation of a β sheet of aminoterminal domain and outward movement of loop 2, loop F, and cys-loop, which are coupled to the M2-M3 linker to pull the channel to open. However, there are still some controversies about the movement of the channel-lining domain M2. Nine angstrom resolution EM structure of a nAChR imaged in the open state suggests that channel opening is the result of rotation of the M2 domain. In contrast, recent crystal structures of bacterial homologues of the cys-loop receptor family in apparently open state have implied an M2 tilting model with pore dilation and quaternary twist of the whole pentameric receptor. An elegant study of the nAChR using protonation scanning of M2 domain supports a similar pore dilation activation mechanism with minimal rotation of M2. This remains to be validated with other approaches including high resolution structure determination of the mammalian cys-loop receptors in the open state.     

Harm reduction for injecting opiate users： an update and implications in China

The harm associated with high-risk injected opiate use and the threat of the HIV epidemic among injecting drug users has become a worldwide problem. Twenty years ago, in the face of a rapid increase in mortality rates among injecting drug users and the upcoming threat of HIV, the first harm-reduction programs were implemented in the Western world. This paper is a literature review describing four forms of harm reduction currently in use in Europe, North America, and Australia. Each represents a reasonable counterapproach to the threat of increased prevalence of HIV among injecting drug users in transitional and developing countries. The paper attempts to explain the concepts behind the most commonly used types of harm reduction and provides a brief overview of the advantages and disadvantages of each and the reasons for their implementation. The main focus of the review is on the definition and the practical aspects of harm reduction; it includes a brief introduction of Chinese harm-reduction efforts and their implications.     

我国患者使用盐酸替扎尼定的不良反应分析

目的分析我国患者使用盐酸替扎尼定不良反应的数量、类型及与剂量的相关性,为该药的临床合理应用提供参考。方法以“替扎尼定”为主题词检索1988年1月至2014年2月间的文献报道,制定严格的文献纳入和排除标准,提取涉及替扎尼定上市后的不良反应信息进行分析。结果替扎尼定的不良反应发生率为32．19％,主要表现为神经系统损害,包括嗜睡、头痛、眩晕,尤其以嗜睡最为多见;循环系统、皮肤损害、胃肠道反应发生较少。中枢性肌强直的患者应用盐酸替扎尼定时,主要不良反应的发生率要高于疼痛性肌痉挛患者。结论我国患者使用替扎尼定的不良反应大多较轻微,适度嗜睡对患者可能有一定帮助。通过降低药物剂量或减慢递增药物剂量的速度可减少严重不良反应的发生。     

Central cholinergic regulation of respiration： nicotinic receptors

Nicotinic acetylcholine receptors （nAChRs） are expressed in brainstem and spinal cord regions involved in the control of breathing. These receptors mediate central cholinergic regulation of respiration and effects of the exogenous ligand nicotine on respiratory pattern. Activation of α4＊ nAChRs in the preBotzinger Complex （preBotC）, an essential site for normal respiratory rhythm generation in mammals, modulates excitatory glutamatergic neurotransmission and depolarizes preBotC inspiratory neurons, leading to increases in respiratory frequency, nAChRs are also present in motor nuclei innervating respiratory muscles. Activation of post- and/or extra-synaptic α4＊ nAChRs on hypoglossal （XII） motoneurons depolarizes these neurons, potentiating tonic and respiratory-related rhythmic activity. As perinatal nicotine exposure may contribute to the pathogenesis of sudden infant death syndrome （SIDS）, we discuss the effects of perinatal nicotine exposure on development of the cholinergic and other neurotransmitter systems involved in control of breathing. Advances in understanding of the mechanisms underlying central cholinergic/nicotinic modulation of respiration provide a pharmacological basis for exploiting nAChRs as therapeutic targets for neurological disorders related to neural control of breathing such as sleep apnea and SIDS.     

Pivotal effects of phosphodiesterase inhibitors on myocyte contractility and viability in normal and ischemic hearts

Phosphodiesterases （PDEs） are enzymes that degrade cellular cAMP and cGMP and are thus essential for regulating the cyclic nucleotides. At least 11 families of PDEs have been identified, each with a distinctive structure, activity, expression, and tissue distribution. The PDE type-3, -4, and -5 （PDE3, PDE4, PDE5） are localized to specific regions of the cardiomyocyte, such as the sarcoplasmic reticulum and Z-disc, where they are likely to influence cAMP/cGMP signaling to the end effectors of contractility. Several PDE inhibitors exhibit remarkable hemodynamic and inotropic properties that may be valuable to clinical practice. In particular, PDE3 inhibitors have potent cardiotonic effects that can be used for short-term inotropic support, especially in situations where adrenergic stimulation is insufficient. Most relevant to this review, PDE inhibitors have also been found to have cytoprotective effects in the heart. For example, PDE3 inhibitors have been shown to be cardioprotective when given before ischemic attack, whereas PDE5 inhibitors, which include three widely used erectile dysfunction drugs （sildenafil, vardenafil and tadalafil）, can induce remarkable cardioprotection when administered either prior to ischemia or upon reperfusion. This article provides an overview of the current laboratory and clinical evidence, as well as the cellular mechanisms by which the inhibitors of PDE3, PDE4 and PDE5 exert their beneficial effects on normal and ischemic hearts. It seems that PDE inhibitors hold great promise as clinically applicable agents that can improve cardiac performance and cell survival under critical situations, such as ischemic heart attack, cardiopulmonary bypass surgery, and heart failure.