慢性气道疾病患者吸入气雾剂使用调查及药学监护

目的:了解患者使用吸入气雾剂的情况,提高药师药学监护水平。方法:调查呼吸内科住院部132例慢性气道疾病患者使用吸入气雾剂的基本情况、既往用药信息和使用吸入气雾剂的操作等,并对数据进行统计和对比分析。结果:所有初次使用吸入气雾剂的93例患者中,23例完全掌握吸入方法(24.73%),36例有1～2项操作错误(38.71%),34例患者有3或3项以上操作错误(36.56%)。93例患者中,低、高学历组吸入方法总掌握率分别为40.00%、81.13%(P<0.01),既往使用过吸入气雾剂的39例患者,曾接受过指导和未经过指导者吸入方法的总掌握率分别为100.00%、44.44%(P<0.01)。所有初次使用压力定量气雾吸入器和干粉吸入器的患者方法掌握率分别为60.71%、67.57%(P>0.05)。结论:经过药师的用药指导,患者能够更加熟练地掌握吸入气雾剂使用方法,药学监护对患者合理用药有重要意义。     

临床药师对干粉吸入剂用药患者实施全程药学监护的效果研究

目的 通过吸入步骤评分表对干粉(DPI)吸入剂用药依从性的调查,评价临床药师对患者实施全程药学监护的效果.方法 本研究选取我院2019年1月～2020年1月收治的60例吸入用药患者,由临床药师实施全程药学监护.采用吸入步骤评分表和吸入剂用药依从性调查问卷表分别对用药监护前后患者的吸入步骤用药依从性进行评分,评价患者对吸...     

药学干预对患者正确使用沙美特罗替卡松粉吸入剂的影响

<正>沙美特罗替卡松粉吸入剂是长效β2受体激动剂沙美特罗(SM)和新型吸入型糖皮质激素丙酸氟替卡松的混合干粉吸入剂,是目前治疗哮喘的唯一双效合一的药物,也成为治疗慢性阻塞性肺疾病(COPD)的一线药物。临床药师在工作中发现许多患者对疾病的认识不足,对沙美特罗替卡松干粉吸入剂的使用方法掌握不当,直接影响了临床疗效。因此自2012年1月临床药师对我院接受沙美特罗替卡松粉吸入剂治疗的患者进行了药学干预,取得了较好的临床效果与社     

药剂师主导的改善COPD患者用药依从性的干预研究（英文）

慢性阻塞性肺疾病(COPD)治疗的用药依从性与疾病控制相关。本文通过调查药剂师对干粉吸入剂(DPI)的使用进行干预后COPD患者吸入技术、满意度和依从性的改善情况,探讨使用干粉吸入剂患者的吸入技术、满意度与用药依从性之间的关系。研究对象为至少使用2个月DPIs的COPD患者,DPIs包括都宝(Turbohaler),准纳器(Discus)和吸乐(Handihaler)。当患者第一次进入研究时,吸入器技术、满意度和依从性等由训练有素的药剂师进行评估。第一次评估后,药剂师通过指导患者吸入剂使用,并针对患者用药满意度调查结果中不满意问题进行解答和干预,并对其进行1个月、3个月进行随访,6个月评估患者干预后吸入技术、满意度和依从性。共有135名患者完成本研究,患者吸入装置使用时间越长错误率越低,依从性越好,而CAT分越高及过去1年内病情加重次数越多,依从性越差。在干预前吸入技术中至少有一个错误的患者比例:都宝86.44%,准纳器76.60%,吸乐54.17%。药师干预后至少有一个错误的患者比例:都宝32.20%,准纳器29.79%,吸乐22.92%。干预后PASAPQ满意度平均分由基线时的74...     

“红围巾关爱行动“对使用干粉吸入剂的COPD患者的健康教育效果

目的 探讨"红围巾关爱行动"对使用干粉吸入剂的COPD患者的健康教育效果。方法 对2014年1月至2016年2月入住安徽医科大学第一附属医院呼吸内科的97例使用干粉吸入剂（DPI）,的COPD患者按随机数字法分为对照组41例与研究组56例,对照组采用常规健康宣教,研究组在此基础上接受"红围巾关爱行动"干预。连续干预2个月后评价两组患者DPI知识知晓率及操作正确率,统计不良反应发生率。结果 研究组DPI知识知晓率及操作正确率分别为70.9%、90.9%,均高于对照组的47.5%、65%,不良反应发生率低于对照组,差异均有统计学意义（P < 0.05）。结论 "红围巾关爱行动"提高了COPD患者DPI知识知晓率、操作正确率及降低了不良反应的发生率。     

慢性阻塞性肺疾病患者吸入用药的药学监护要点

目的:对慢性阻塞性肺疾病患者使用吸入药物进行药学监护,提高患者用药依从性及治疗效果。方法:结合治疗方案,指导慢性阻塞性肺疾病患者正确使用吸入药物,从选择药物到评价疗效进行全程药学监护。结果:通过药学监护,患者能够熟练地掌握吸入药物使用技巧,提高了依从性和治疗效果。结论:慢性阻塞性肺疾病患者吸入用药的技巧掌握率低,专业人员的指导对提高疗效和生活质量十分重要,药学监护应成为治疗过程中的一个重要环节。     

成人支气管哮喘患者氧气驱动雾化吸入的药学监护

目的调查成人支气管哮喘患者氧气驱动雾化吸入的使用情况与药学监护现状。方法对我院呼吸内科进行氧气驱动雾化吸入的成人支气管哮喘患者的基本情况、操作方法进行调查,并对数据进行统计、分析。结果未经过药学教育初次使用雾化吸入的63例患者,仅10例（15.87%）能基本掌握雾化吸入操作,经过药学教育后有43例（68.25%）能基本掌握,经过药学教育的初次使用雾化吸入的68例患者中有53例（77.94%）能基本掌握操作方法,二次教育后仅余3例（4.41%）患者未掌握操作方法。经药师三次教育后大部分患者都能掌握操作方法。结论经过药学教育后大部分患者都能基本掌握雾化吸入操作方法,药师的药学教育对于患者掌握雾化吸入的操作方法十分重要。     

布地奈德福莫特罗干粉吸入剂联合督导方法治疗哮喘28例

目的 观察布地奈德福莫特罗干粉吸入剂联合督导方法治疗支气管哮喘的疗效。方法 选取2012年2月至2013年8月间医院就诊的轻中度持续发作、未曾使用过干粉吸入剂哮喘患者63例,随机分成试验组28例(督导方法吸入布地奈德福莫特罗粉吸入剂160μg/4.5μg,1吸/次、2次/日)与对照组35例(非督导方法吸入布地奈德福莫特罗粉吸入剂160μg/4.5μg,1吸/次、2次/日),比较两组患者治疗前后哮喘控制测试(ACT)评分,声音嘶哑、骨骼肌震颤、口腔真菌感染发生率,规律吸入药物、规律吸入后漱口的比例。结果 第1个月复诊时,试验组ACT评分高于对照组,规律吸入药物及规律吸入后漱口比例均高于对照组(P<0.05);第2,3个月复诊时两组间ACT问卷评分、规律吸入药物及规律吸入后漱口比例,无统计学差异(P>0.05);第1,2,3个月复诊时声音嘶哑、骨骼肌震颤、口腔真菌感染发生率组间比较,均无统计学差异(P>0.05)。结论 干粉吸入督导治疗有助于哮喘患者在短期内得到较好的治疗效果,能规范患者应用吸入药物的方法,减少潜在的药品不良反应。     

咳喘药学门诊的构建及实践

目的 探讨浙江大学医学院附属杭州市第一人民医院咳喘药学门诊的实践模式。方法 开设咳喘药学门诊,配备相应的软硬件设施,建立咳喘药学服务模式。收集2020年12月1日—2022年8月31日在医院咳喘药学门诊就诊的患者2 357例,分析其一般资料,患者根据吸入剂视频自我学习后再由药师进行指导,评估药师干预前后的患者吸入剂使用技能差异。收集2020年12月1日—2021年7月31日在医院咳喘药学门诊就诊的慢性阻塞性肺疾病患者345例,依据盲抽法分为每30 d随访组(n=173),每15 d随访组(n=172),比较随访第1,3,6,12个月的Morisky用药依从性量表(MMAS-8)评分差异。结果 2 357例就诊患者中,男性1 213例(占51.46%),女性1 144例(占48.54%);年龄≥60岁1 309例(占55.54%),年龄40~59岁563例(占23.89%),年龄20~39岁402例(占17.06%),年龄14~20岁32例(占1.36%),年龄＜14岁51例(占2.16%);患者主要疾病类型为慢性阻塞性肺疾病(占55.38%)、哮喘(占20.73%);用药频率较高的为布地奈德福莫特罗吸入粉雾剂(占37.08%)、布地格福吸入气雾剂(占25.84%)。药师在患者视频教学的基础上进行干预后患者的吸入剂使用技能掌握情况优于患者通过视频自我学习的掌握情况,干预前评分为5.360±1.208,干预后评分为7.890± 0.356,两者存在显著性差异(P＜0.05)。随访1个月时,15 d随访组的MMAS-8评分为6.310±1.079,30 d随访组的MMAS-8评分为5.250±0.977,两者存在显著性差异(P＜0.05),随访3,6,12个月的2组患者的MMAS-8评分无显著性差异。结论 咳喘药学门诊的建立推进了药学与呼吸临床学科的融合,提高了患者用药依从性。     

吸入剂新型二维码视频药学教育模式应用效果及影响因素分析

目的 探讨吸入剂新型二维码视频药学教育模式在临床的应用效果.方法 选取2018年7月至12月医院呼吸科门诊使用布地奈德福莫特罗粉吸入剂的慢性气道疾病患者360例,按奇偶数法分为观察组和对照组,各180例.观察组患者予二维码视频药学教育后用药,对照组患者自行阅读药品说明书用药.结果 观察组平均药学教育时间为(4.44±2...     

Comparison of the lung absorption of FK224 inhaled from a pressurized metered dose inhaler and a dry powder inhaler by healthy volunteers.

FK224 is a cyclopeptide drug with poor oral absorption due to proteolysis in the gastrointestinal tract. The objectives of this study were to investigate the absorption of FK224 from the lung in healthy volunteers, and compare the pharmacokinetic profiles of FK224 after inhalation from a pressurized metered dose inhaler (pMDI) and dry powder inhaler (DPI). The pMDI (Suspension type, 1 mg as FK224/puff) and DPI (4 mg and 10 mg as FK224/capsule, using Spinhaler as the device) were developed by formulating the same micronized particles of FK224 which were premixed with beta-cyclodextrin (beta-CyD) to improve the solubility of FK224. In the case of pMDI, 1, 4 or 8 mg was inhaled by the corresponding number of puffs with the pMDI. In addition, the in vitro drug delivery characteristics of the inhalers were evaluated using a multistage liquid impinger. In both inhalers, it was observed that FK224 could be absorbed into the systemic circulation from the lungs of the healthy volunteers, and the AUC and C(max) were proportionally increased depending on the emitted dose after inhalation. However, the pharmacokinetic (PK) parameters for DPI were significantly higher than that of pMDI, in spite of usage of the same fine particles for the formulations in both inhalers. Based on the distribution from the in vitro examination, the fine particle dose, which is defined as the dose region delivered as particles <3.8 microm, was calculated from the emitted dose inhaled by the healthy volunteers. It was found that the PK parameters for both inhalers were proportionally increased depending on the predicted fine particle dose regardless of the type of inhaler. This suggests that the absorption from the lung is influenced by the fine particle dose. We concluded that DPI is a suitable inhaler for FK224, and the alveolus, which is generally known as the site of action of the fine particles, is a possible absorptive site for FK224.     

Agonistic actions of DPI (2-(3,4-dihydroxyphenylimino)-imidazolidine) on alpha-adrenoceptors and dopamine receptors

Some of the pharmacological actions of 2-(3,4-dihydroxyphenylimino)-imidazolidine (DPI) were studied in vivo and vitro. DPI (1 nM-100 micro M) had a similar affinity but a lower intrinsic activity on alpha-adrenoceptors in rabbit aortic strips to noradrenaline (1 nM-10 micro M). DPI did not affect the uptake of [3H]noradrenaline in guinea-pig isolated atria. The effects of DPI on dopamine receptors were examined in the dog coronary and renal vasculature and in the rat isolated, perfused kidney. In the dog coronary vasculature DPI (0.005-10 micrograms, i.a.), like dopamine (5-50 micrograms, i.a.), caused an increase in coronary blood flow which was antagonized by the dopamine receptor antagonist, ergometrine. In the renal vasculature of both the rat and the dog, dopamine (5-50 micrograms, i.a.) caused vasodilatation but there was no evidence of an effect of DPI on dopamine receptors. It appears that DPI is a selective agonist for dopamine receptors in the coronary vasculature.     

Drug delivery characteristics of Bricanyl TurbohalerTM dry powder inhalers

The Turbohaler^TM is the one multidose reservoir type dry powder inhaler (DPI) with significant clinical usage but there is little information on the precision of its single dose delivery characteristics. The single dose delivery efficiency of terbutaline sulphate (nominally 500 μg) from two batches of Bricanyl Turbohalers^TM (11 and 59 devices) has therefore been studied at air flow rates of 28–30 and 60 1 min ⁻¹ which are clinically relevant test conditions for this DPI. At 60 1 min⁻¹ statistically significant differences both within and between batches were obtained for emitted dose (± SD, n = 110, 130), 421 ± 73, 387 ± 58μg and fine particle dose (0.5–6.4 μm MMAD), 249 ± 41, 214 ± 44μg. These data imply an emitted dose range of ± 50% and a fine particle dose range of ± 70% from this DPI system. Through-life total dose emission in terms of the average values remain consistent. Reducing air flow rates to approx. 30 1 min⁻¹ lowered the mean emitted dose by about one third with the clinically important fine particle dose being reduced 3-fold to 59 ± 25 μg; this underlines the likely sensitivity of effective delivery, to patients' lung function. These results reinforce the need to provide single dose data at clinically relevant flow rates in the assessment of DPI performance. Expressing data as mean performance for a cumulative series of dose units smooths down this single dose variability by a factor of two.     

Effects of DPI (2-(3,4-Dihydroxyphenylimino)-imidazolidine) on prejunctional α-adrenoceptors and prejunctional dopamine receptors in the rabbit ear artery

The effects of DPI on transmitter noradrenaline release were examined in rabbit isolated ear arteries previously incubated in [ 3H ]noradrenaline. DPI (0.1 mumol/l) reduced transmitter release with periarterial electrical stimulation at 1 Hz (1 ms pulses, supramaximal voltage for 30 s), which is consistent with an agonistic effect of DPI on prejunctional alpha-adrenoceptors. At stimulation frequencies of 2 or 5 Hz DPI alone did not affect release, however in the presence of phentolamine (3 mumol/l, which increased release per se) DPI again significantly reduced release; this effect was blocked by metoclopramide (1 mumol/l) indicating an agonistic effect of DPI on prejunctional dopamine receptors.     

The action of microelectrophoretically applied (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI) on single cortical neurones.

1. The technique of microelectrophoresis was used in order to compare the actions of the imidazoline derivative, (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI), with those of dopamine and phenylephrine on single neurones in the cerebral cortex of the rat anaesthetized with halothane. 2. DPI and phenylephrine were almost exclusively excitatory, whereas dopamine could evoke both excitatory and depressant responses. 3. In the case of excitatory responses, DPI appeared to be more potent than dopamine, and was approximately equipotent with phenylephrine. 4. The dopamine antagonist, haloperidol, could discriminate between excitatory responses to DPI and dopamine: responses to dopamine were abolished, whereas responses to DPI, and to a control agonist, acetylcholine, were unaffected. 5. The alpha-adrenoceptor antagonist, phenoxybenzamine, antagonized equally excitatory responses to DPI and phenylephrine. Responses to acetylcholine were not affected. 6. It is concluded that DPI does not stimulate dopamine receptors on cortical neurones; the excitatory responses of these cells to DPI may be mediated by alpha-adrenoceptors.     

Induction of apoptosis and modulation of production of reactive oxygen species in human endothelial cells by diphenyleneiodonium

Diphenyleneiodonium (DPI) inhibits activity of flavoenzymes like NADPH oxidase, the major source of superoxide anion in cardiovascular system, but affects also other oxidoreductases. Contradictory data have been published concerning the effect of diphenyleneiodonium on the production of reactive oxygen species in cells, both inhibitory and stimulatory action of DPI being reported. We have examined the effect of DPI on the cellular production of reactive oxygen and nitrogen species (ROS/RNS) and on the proliferation and apoptosis of human vascular endothelial cells. We found increased oxidation of ROS-sensitive probes (dihydrorhodamine 123 and 2',7'-dichlorodihydrofluorescein diacetate) when DPI (20 microM-100 microM) was present in the treated cells. However, oxidation of the fluorogenic probes was inhibited if DPI (20 microM-100 microM) was removed from the reaction medium after cell preincubation. These results suggest an artifactual oxidation of the fluorogenic probes by DPI or its metabolites. A similar pattern of influence of DPI on the production of NO (measured with 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate) was observed. Modulation of generation of reactive oxygen and nitrogen species in DPI-treated cells influenced the nitration of tyrosine residues of cellular proteins, estimated by Western blotting. Decreased level of nitration generally paralleled the lowered production of ROS. A decreased 3-(4,5-dimethylthiazolyl)-3-3(4-sulphophenyl) tetrazolium (MTT) reducing activity of cells for was observed immediately after 1h treatment of human endothelial cells with DPI (1 microM-100 microM), in spite of lack of changes in cell viability estimated by other methods. These results point to a next limitation of MTT in estimation of viability of cells treated with oxidoreductase inhibitors. DPI inhibited the proliferation of HUVECs as well as immortalized cell line HUVEC-ST, as assessed by acid phosphatase activity test and measurement of total nucleic acid content. Proapoptotic action of DPI was observed 12 h after incubation with this compound.     

THE INHIBITION OF NITRIC OXIDE-MEDIATED RELAXATIONS IN RAT AORTA AND ANOCOCCYGEUS MUSCLE BY DIPHENYLENE IODONIUM

1. The effects of diphenylene iodonium (DPI), an inhibitor of reduced nicotinamide adenine dinucleotide phosphate-dependent oxidases (which generate superoxide anions), were studied on nitric oxide (NO)-mediated responses in isolated preparations of the rat aorta and anococcygeus muscle. 2. In aortic rings, the endothelium-dependent relaxant action of acetylcholine was reduced by DPI (0.3–10 μmol/L) in a concentration-dependent manner and abolished by the NO synthase (NOS) inhibitor L-nitro-N^G-arginine methylester (l-NAME; 100 μmol/L). Relaxations induced by sodium nitroprusside (SNP) or NO were not affected by DPI or l-NAME. 3. In anococcygeus muscles, DPI (0.3–10 μmol/ L) as well as l-NAME (5–100 μmol/L) produced concentration-dependent reductions of relaxations produced by nitrergic nerve stimulation. Relaxations induced by NO and SNP were not affected by either DPI or l-NAME. l-Arginine (1 mmol/L) prevented the reduction of nitrergic relaxations by l-NAME but not by DPI. 4. Contractions of anococcygeus muscles elicited by exogenous noradrenaline (1 μmol/ L) were not affected or were inhibited by DPI (0.3–10 μmol/L), but the contractions elicited by noradrenergic nerve stimulation were significantly enhanced by DPI and l-NAME. When noradrenergic contractions had already been maximally enhanced by l-NAME (100 μmol/L), DPI produced no further enhancement. l-Arginine (1 mmol/L) prevented the enhancement of noradrenergic contractions by l-NAME but not by DPI. 5. The efflux of radioactivity induced by field stimulation from anococcygeus muscles previously incubated with [³H]-noradrenaline was not affected by either DPI or l-NAME. 6. Superoxide dismutase (SOD, 100 U/mL) had no significant effects on noradrenergic contractions, nitrergic relaxations, relaxations induced by NO or the actions of DPI in the rat anococcygeus muscle. 7. The results suggest that the effects of DPI in reducing the NO-mediated relaxations produced by acetylcholine in rat aortic rings and stimulation of nitrergic nerves in the rat anococcygeus muscle are due to the inhibition of NOS in these tissues. The effects of DPI were not sensitive to l-arginine, and thus the mechanism of inhibition of NOS differs from that of l-NAME.     

Evidence that the purported dopaminergic agonist (3,4-dihydroxyphenylimino)-2-imidazolidine (DPI) may reduce rat striatal dopamine turnover by an alpha 2-adrenergic mechanism

The potent alpha-adrenergic agonist DPI, which has also been claimed to be a selective dopaminergic agonist, was shown to reduce rat striatal dopamine (DA) synthesis, DA utilization and DA metabolism following intraperitoneal administration (25 mumol/kg). An analytical procedure for the determination of DPI was developed and its application showed that DPI did not penetrate into the brain in substantial amounts. The possibility of a direct stimulatory action upon striatal presynaptic DA receptors was excluded by the demonstration that DPI lacked effectiveness both in the gamma-butyrolactone model and following intrastriatal administration. The selective alpha-adrenergic agonists phenylephrine (alpha 1) and tramazoline (alpha 2) decreased and increased DA metabolism, respectively, the yohimbine-induced increase being antagonized by DPI. The carbon-bridge analogue (3,4-dihydroxybenzyl)-2-imidazoline (DHBI) had about the same activity as DPI, whereas the potential DPI metabolite (4-hydroxy-3-methoxyphenylimino)-2-imidazolidine (HMPI) was without effect upon striatal DA metabolism. The results are discussed in relation to the remarkable resemblance with the literature data concerning clonidine. It is concluded that the DPI-elicited attenuation of striatal DA turnover is, in all likelihood, the result of a stimulation of alpha 2-adrenoceptors possibly located within the central nervous system. The results cast some doubt on the designation of DPI as a selective DA-inhibitory receptor agonist.     

Cardiac electrophysiologic effects of orally administered DPI 201-106 in conscious canines: effects of pharmacologic autonomic blockade or cardiac transplantation

This study assessed the cardiac electrophysiologic effects of DPI 201-106 (DPI), a novel orally absorbable positive inotropic agent, the administration of which has been associated with electrocardiographic (ECG) QT and T-wave changes. In the intact conscious dog, oral administration of both 8 and 16 mg/kg DPI produced marked sinus cycle length prolongation (8 mg/kg, + 11%; 16 mg/kg, + 9%) within 60 min of DPI administration (p less than 0.05 vs. baseline). DPI also tended to prolong right atrial refractory periods, and increase sinus node recovery time. In addition, DPI exhibited a negative dromotropic effect on the atrioventricular (AV) node, prolonging both AV node effective and functional refractory periods and tending to increase the minimum atrial paced cycle length at which AV conduction of 1:1 was maintained. DPI also significantly increased right ventricular effective refractory period (ERP) at both doses studied and increased ventricular functional refractory period (FRP) at the 16-mg/kg dose. Finally, although DPI administration was associated with QT interval prolongation, this effect was slight when corrected for sinus cycle length (SCL) (QTc, +3%). When administered concomitantly with propranolol and atropine or after surgical cardiac denervation, DPI-induced electrophysiologic changes were largely attenuated or abolished. Thus, findings in this study indicate that the apparent cardiac electrophysiologic effects of DPI are predominantly of neurally mediated origin in this animal model.     

The comprehensive influence of firm-level factors on drug product internationalization of Chinese pharmaceutical firms

Drug product internationalization (DPI) can be affected by multiple firm-level factors. However, existing studies mainly focus on a single or several factors and the deviation generated by the factors’ effects on each other has been neglected. We aimed to study the comprehensive influences of firm-level factors on Chinese pharmaceutical firms that chose the DPI mode. Student’s t tests and Chi Square tests were used to explore the differences between firms with or without DPI modes. Then, logistic regression analysis was used to explore the comprehensive impacts of these 16 variables.Through empirical research, we found the factors influencing the DPI mode of Chinese pharmaceutical enterprises and the firm-level factors that influenced DPI mode selection. This study showed that the capacity of enterprise’s innovation and knowledge absorption were related to the mode selection. Moreover, the education of the top management team significantly contributed to the DPI mode selection of pharmaceutical firms. This study also provided theoretical and empirical evidence for pharmaceutical enterprises when choosing their DPI mode.The internationalization of Chinese pharmaceutical firms remained at the early stage. However, the internationalization of drug products from China would affect the international pharmaceutical supply in the long term.