α-糜蛋白酶雾化吸入与氨溴索静脉给药配合抗菌药物对脑梗死患者伴肺部感染的疗效及其对症状改善的影响

目的:评价α-糜蛋白酶雾化吸入与氨溴索静脉给药配合抗菌药物对脑梗死患者伴肺部感染的疗效及其对症状改善的影响。方法:选取2016年7月—2017年9月期间诊治的脑梗死并发肺部感染患者102例资料,按治疗药物的不同将其分为对照组和观察组(每组51例);对照组患者给予相应敏感抗菌药物治疗,观察组患者在对照组基础上加用α-糜蛋白酶雾化吸入与氨溴索静脉注射联用治疗,比较两组患者治疗后肺部感染的总有效率、临床症状复常时间差异。结果:观察组患者治疗后肺部感染的总有效率为96.08%高于对照组为80.39%(P<0.05),临床症状复常时间早于对照组(P<0.05)。结论:采用α-糜蛋白酶雾化吸入与氨溴索静脉给药配合抗菌药物治疗脑梗死患者并发肺部感染的疗效较为确切,有效改善了症状,提高了临床疗效。     

雾化吸入治疗中应注意的几个问题

雾化吸入疗法是临床上较好的物理与化学治疗相结合的祛痰消炎手段，具有操作简单，药物直达病灶。局部病灶药物浓度高，安全性好，毒副作用小的优点。雾化吸入是治疗呼吸道及肺部感染性病变常用的给药途径，常用药物有消除气管及支气管内蛋白分泌物的糜蛋白酶，稀释痰液的药物，解除支气管痉挛的药物，预防和治疗哮喘而使用的激素类药物，以及抗生素和利尿剂。     

泛耐药铜绿假单胞菌感染的抗感染思路分析

目的 探讨泛耐药铜绿假单胞菌肺炎的药物治疗方案。方法 以临床药师参与一例大面积烧伤患者的泛耐药铜绿假单胞菌肺炎的抗感染方案为例，结合最新临床研究进展，探讨抗菌药物雾化吸入在治疗泛耐药细菌导致的肺部感染中的应用。 结果 泛耐药铜绿假单胞菌导致的肺部感染通常选择联合治疗，抗菌药物雾化吸入作为一种联合或补充治疗，可以提高肺部药物浓度，减少全身不良反应，但使用时仍需慎重选择临床适应症。 结论 临床药师应积极参与抗感染方案的制定，针对患者制定个体化的给药方案。     

呼吸系统疾病治疗用雾化吸入抗菌药物的研究进展

传统的抗菌药物给药方式(口服或静脉注射)由于药物的理化性质和宿主解剖学特点,感染部位往往达不到有效的抗菌浓度,导致了治疗的失败。雾化吸入疗法因药物直接作用于靶器官,具有起效迅速、疗效佳、全身不良反应少、不需要患者刻意配合等优势,成为治疗呼吸系统相关疾病较为理想的给药方法。目前抗菌药物吸入制剂只有妥布霉素、氨曲南和多黏菌素,正在研制的有环丙沙星、左氧氟沙星、阿米卡星、两性霉素B、万古霉素等。国外在20世纪40年代开始对吸入抗菌药物进行研究,相对国外的研究,国内的相关报道还较少,因此,为给呼吸系统疾病的防治带来临床新路径,对近年来国内外雾化吸入抗菌药物的药效/药动学研究进展进行综述。     

雾化吸入药物间配伍相容性的研究进展

雾化给药是指将药物直接递送到肺组织而发挥治疗作用,是治疗呼吸系统疾病的常用给药方式。2种或多种药物混合后同时雾化可缩短给药时间,但混合物的潜在不相容性会导致药物安全性降低并影响治疗疗效,明确雾化吸入药物间的配伍相容性,是保证临床安全用药的前提。该文对目前国内上市雾化吸入药物间配伍相容性的研究进展进行综述,以期为雾化吸入药物的临床安全使用和未来研究提供参考。     

雾化吸入给药临床研究及进展

雾化吸入给药是指通过雾化装置将药物分散成悬浮于气体中的细小雾滴或微粒,通过吸入的方式沉积于呼吸道和(或)肺部,从而达到呼吸道局部的治疗作用.与其他给药方式相比,雾化吸入给药具有起效快、局部药物浓度高、用药量少、应用方便及全身不良反应少等优点,已成为治疗呼吸系统疾病的主要给药方式之一.本文就雾化吸入治疗的应用、雾化器的种...     

405株肺部感染患者致病菌的分布及其对抗菌药物合理使用的影响

目的:探究细菌培养与药敏试验结果对呼吸内科肺部感染患者抗菌药物合理使用的影响。方法:选取2016年1月—2018年6月间呼吸内科肺部感染患者775例资料,统计其患者痰液标本中细菌培养、分离及其药敏实验结果,分析致病菌对不同抗菌药物的耐药性。结果:775例肺部感染患者中,分离出病原菌405株其检出率为52.26%,其中排前5位的致病菌如大肠埃希菌、铜绿假单胞菌、肺炎克雷伯菌、金黄色葡萄球菌和奇异变形杆菌的检出率依次为28.89%、12.84%、8.89%、7.16%和4.94%;大肠埃希菌、肺炎克雷伯菌、奇异变形杆菌对西林类、头孢类、沙星类抗菌药物的耐药性相对较高,而铜绿假单胞菌对替卡西林的耐药性较高,对所检测其他抗菌药物的耐药性较低。结论:肺部感染患者致病菌对多数抗菌药物均具有多重耐药性,临床应尽早检测明确致病菌及其对抗菌药物的耐药性,以确保抗菌药物的合理使用,提高其临床疗效。     

雾化吸入给药的临床应用现状及研究进展

吸入疗法已经成为治疗呼吸系统疾病的常用治疗方法,主要包括压力定量吸入、干粉吸入和雾化吸入给药等。其中雾化吸入给药由于具有明显的优势,近几年来其临床应用药物种类、治疗疾病类型等都有了进一步的发展。笔者就雾化吸入给药的原理、现状及相关临床应用进展等进行综述。     

氨溴索不同给药方式治疗婴幼儿下呼吸道感染疗效观察

目的观察氨溴索的不同给药方式治疗婴幼儿下呼吸道感染的疗效。方法选择婴幼儿下呼吸道感染患儿186例,随机分为雾化组64例,静脉滴注组62例,口服组60例,临床观察三组病例咳嗽、气促、肺部体征消失情况。结果雾化组患儿的咳嗽、气促、肺部体征消失时间明显少于静脉滴注组和口服组。经统计学检验,差异有统计学意义（P〈0.05）。静脉滴注组和口服组疗效差异无统计学意义。结论氨溴索雾化吸入治疗婴幼儿下呼吸道感染疗效显著,起效快,是首选给药方式。     

泛耐药铜绿假单胞菌感染的抗感染思路分析

目的 探讨泛耐药铜绿假单胞菌肺炎的药物治疗方案。方法 以临床药师参与一例大面积烧伤患者的泛耐药铜绿假单胞菌肺炎的抗感染方案为例,结合最新临床研究进展,探讨抗菌药物雾化吸入在治疗泛耐药细菌导致的肺部感染中的应用。 结果 泛耐药铜绿假单胞菌导致的肺部感染通常选择联合治疗,抗菌药物雾化吸入作为一种联合或补充治疗,可以提高肺部药物浓度,减少全身不良反应,但使用时仍需慎重选择临床适应症。 结论     

Aspects of pulmonary drug delivery strategies for infections in cystic fibrosis – where do we stand?

Introduction: Cystic fibrosis (CF) is the most common life-shortening hereditary disease among Caucasians and is associated with severe pulmonary damage because of decreased mucociliary clearance and subsequent chronic bacterial infections. Approximately 90% of CF patients die from lung destruction, promoted by pathogens such as Pseudomonas aeruginosa. Consequently, antibiotic treatment is a cornerstone of CF therapy, preventing chronic infection and reducing bacterial load, exacerbation rates and loss of pulmonary function. Many drugs are administered by inhalation to achieve high pulmonary concentration and to lower systemic side effects. However, pulmonary deposition of inhaled drugs is substantially limited by bronchial obstruction with viscous mucus and restrained by intrapulmonary bacterial biofilms.

Areas covered: This review describes challenges in the therapy of CF-associated infections by inhaled antibiotics and summarizes the current state of microtechnology and nanotechnology-based pulmonary antibiotic delivery strategies. Recent and ongoing clinical trials as well as experimental approaches for microparticle/nanoparticle-based antibiotics are presented and their advantages and disadvantages are discussed.

Expert opinion: Rapidly increasing antimicrobial resistance accompanied by the lack of novel antibiotics force targeted and more efficient use of the available drugs. Encapsulation of antimicrobials in nanoparticles or microparticles of organic polymers may have great potential for use in CF therapy.     

吸入型平喘药的人体血药浓度测定方法的研究进展

吸入型平喘药包括吸入型糖皮质激素、吸入β受体激动剂和吸入M受体阻断剂,是支气管哮喘与慢性阻塞性肺病首选和常用治疗药物。吸入型平喘药的原研药物大多价格昂贵,然而其仿制药市场份额与原研药物相比却极其微小,主要原因在于现有的吸入平喘药仿制药在疗效和安全性上难以与原研药物保持一致。为了保障吸入平喘药的临床疗效与安全性,有必要进行相应的生物等效性评价研究。这就需要体内药物分析方法提供支持。然而,吸入平喘药因给药剂量低、给药途径特殊等原因而具有血药浓度极低的特点,这使其定量检测具有一定困难。因此,开发和优化吸入型平喘药血药浓度测定方法具有重要意义。本文综述了国内外吸入平喘药血药浓度测定方法,为其临床药动学研究和生物等效性评价提供依据。     

Inhaled prostanoids in the therapy of pulmonary hypertension

Prostacyclin and prostacyclin analogues are potent vasodilators and possess antithrombotic, anti-inflammatory and antiproliferative properties. These properties qualify them as efficient drugs for the treatment of pulmonary hypertension, a life-threatening illness characterized by an increase in artery pressure and vascular resistance in the pulmonary circulation. Diseased pulmonary vessels show specific remodeling with intimal fibrosis, medial hypertrophy, and adventitial thickening, as well as functional changes characterized by vasoconstriction and in situ thrombosis. The intravenous administration of prostacyclin is a well-established therapy option in severe pulmonary hypertension. However, lack of pulmonary and intrapulmonary selectivity can lead to life-threatening pulmonary and systemic side effects. Therefore, the application of prostanoids by inhalation had been proposed. Several studies with inhaled iloprost, a stable prostacyclin analogue, demonstrated preferential and potent vasorelaxation in the pulmonary circulation. In a randomized, double-blind, placebo controlled, multicenter study in 203 patients with pulmonary hypertension inhaled iloprost showed significant improvement of exercise capacity and pulmonary hemodynamics with excellent tolerability and safety. Consequently, inhaled iloprost has been approved in many countries for treatment of severe pulmonary hypertension. A major drawback of inhaled iloprost, however, is the short half-life and hemodynamic effect (30 to 60 min) demanding multiple daily inhalation manoeuvres (up to nine times). Strategies for further improvement of inhaled prostanoid therapy include use of prostacyclin analogues with longer half-life (e.g., treprostinil), combinations with oral drugs (e.g., phosphodiesterase inhibitors or endothelin receptor antagonists) and development of aerosolized controlled release formulations such as liposomes and nanoparticles. The therapy with prostacyclin and its analogues is a main pillar in the treatment of pulmonary hypertension, giving new hope to many patients suffering from this terrible disease. With inhaled iloprost, a new drug has enlarged the scope of aerosol therapies for treatment of pulmonary and systemic diseases.     

Frontrunners in novel pharmacotherapy of COPD

The mainstay of current drug therapy is long-acting bronchodilators; several longer acting inhaled beta(2)-agonists and muscarinic antagonists (and combinations) are now in development. No treatments reduce the progression or suppress the inflammation of COPD. With better understanding of the inflammatory and destructive process, several new targets have been identified. Several mediator antagonists tested in COPD have been disappointing, but of CXCR2 antagonists that block pulmonary neutrophil and monocyte recruitment may be more promising. Broad spectrum anti-inflammatory drugs may be more effective, and include inhibitors of PDE4, p38 MAPK and NF-kappaB, but side effects will be a major limitation so that inhaled delivery will be necessary. Perhaps the most promising approach is reversal corticosteroid resistance through increasing HDAC2 activity. This may be achieved by theophylline-like drugs, more effective antioxidants and non-antibiotic macrolides.     

Effective inhaled drug administration to mechanically ventilated patients

Inhaled therapy is commonly employed in mechanically ventilated patients with chronic obstructive pulmonary disease or asthma. The efficacy of inhaled drugs is comparable to that achieved with systemic routes of administration, but the dose of drug required to achieve a therapeutic effect is generally much smaller. Moreover, limited systemic absorption of inhaled drugs minimises systemic side effects. Aerosol administration to ventilated patients differs from that in ambulatory patients in several respects. Optimal techniques for using pressurised metered-dose inhalers and nebulisers in ventilator circuits have been developed. With these techniques, the efficiency of inhaled drug delivery in mechanically ventilated patients is now comparable to that in ambulatory patients. Pressurised metered-dose inhalers are chiefly used to deliver bronchodilator and corticosteroid aerosols, and are more efficient and convenient to use than nebulisers for routine therapy in ventilated patients. However, nebulisers are more versatile and are employed to generate aerosols of bronchodilators, corticosteroids, antibiotics, prostaglandins, surfactant and mucolytic agents. Improvements in drug formulations and the design and efficiency of aerosol generating devices have led to increasing application of inhaled therapies in mechanically ventilated patients.     

Management of acute exacerbations of chronic obstructive pulmonary disease in the elderly : an appraisal of published evidence

Chronic obstructive pulmonary disease (COPD) is a debilitating disease with rising worldwide prevalence. Exacerbations of COPD cause significant morbidity and become more common with advancing age. Healthcare providers caring for elderly patients should therefore be familiar with effective treatments for exacerbations of COPD. An extensive body of literature has identified several effective drug therapies for exacerbations. These drugs include inhaled bronchodilators, systemic corticosteroids and antibacterials. The two main classes of inhaled bronchodilators are beta-adrenoceptor agonists and anticholinergics. These drugs optimise lung function during exacerbations, with neither class demonstrating clear superiority over the other. Systemic corticosteroids are effective when used either for inpatient or outpatient treatment of exacerbations. They hasten recovery from exacerbations and reduce relapse rates. Antibacterials decrease morbidity from exacerbations and may decrease mortality in the more severe exacerbations. Other effective therapies for the treatment of acute exacerbations of COPD include oxygen and non-invasive ventilation. Oxygen can be safely administered in acute exacerbations associated with hypoxaemia, with titration of oxygen delivery to a goal oxygen saturation of 90%. Non-invasive ventilation reduces the morbidity and mortality associated with acute exacerbations complicated by hypercapnic respiratory failure. Strategies to prevent COPD exacerbations include smoking cessation, long-acting inhaled beta-adrenoceptor agonists, inhaled long-acting anticholinergics, inhaled corticosteroids and vaccination. Mucolytic agents, pulmonary rehabilitation, and case management programmes may also reduce exacerbation risk, but the current evidence supporting these interventions is weaker.     

The effect of respiratory disorders on clinical pharmacokinetic variables

Respiratory disorders induce several pathophysiological changes involving gas exchange and acid-base balance, regional haemodynamics, and alterations of the alveolocapillary membrane. The consequences for the absorption, distribution and elimination of drugs are evaluated. Drug absorption after inhalation is not significantly impaired in patients. With drugs administered by this route, an average of 10% of the dose reaches the lungs. It is not completely clear whether changes in pulmonary endothelium in respiratory failure enhance lung absorption. The effects of changes in blood pH on plasma protein binding and volume of distribution are discussed, but relevant data are not available to explain the distribution changes observed in acutely ill patients. Lung diffusion of some antimicrobial agents is enhanced in patients with pulmonary infections. Decreased cardiac output and hepatic blood flow in patients under mechanical ventilation cause an increase in the plasma concentration of drugs with a high hepatic extraction ratio, such as lidocaine (lignocaine). On a theoretical basis, hypoxia should lead to decreased biotransformation of drugs with a low hepatic extraction ratio, but in vivo data with phenazone (antipyrine) or theophylline are conflicting. The effects of disease on the lung clearance of drugs are discussed but clinically relevant data are lacking. The pharmacokinetics of drugs in patients with asthma or chronic obstructive pulmonary disease are reviewed. Stable asthma and chronic obstructive pulmonary disease do not appear to affect the disposition of theophylline or beta 2-agonists such as salbutamol (albuterol) or terbutaline. Important variations in theophylline pharmacokinetics have been reported in critically ill patients, the causes of which are more likely to be linked to the poor condition of the patients than to a direct effect of hypoxia or hypercapnia. Little is known regarding the pharmacokinetics of cromoglycate, ipratropium, corticoids or antimicrobial agents in pulmonary disease. In patients under mechanical ventilation, the half-life of midazolam, a new benzodiazepine used as a sedative, has been found to be lengthened but the underlying mechanism is not well understood. Pulmonary absorption of pentamidine was found to be increased in patients under mechanical ventilation. Pharmacokinetic impairment does occur in patients with severe pulmonary disease but more work is needed to understand the exact mechanisms and to propose proper dosage regimens.     

Recent advances in pulmonary hypertension therapy

Cardiovascular anesthesiologists have traditionally resorted to using intravenous therapy in the operating room to manipulate hemodynamics and the determinants of cardiac output and systemic vascular resistance during cardiac surgery. General anesthesia involves the administration of both intravenous and inhaled drug therapy to achieve the desired goals, i.e. analgesia, amnesia, muscle relaxation and blockade of autonomic activity. Anesthesiologists are the experts in the use and titration of drugs that are administered through the inhaled route. However, this method of drug delivery presents many challenges, notably timing, dosage accuracy, rapid titratability and consistency of drug delivery. Arguably the most rapid method of treating acute reactive pulmonary vasculature would be by drugs that directly act upon the pulmonary endothelium. In the operating room, pulmonary hypertension and right ventricular failure are high predictors of morbidity and mortality and present significant challenges to the anesthesiologist. In this article, we will focus on advances in inhaled therapy of these conditions, including concerned recent patents. This review will focus on some of the advances in the pharmacology of inhaled drugs that are being used to treat pulmonary hypertension, right and left ventricular failure in the perioperative setting.     

Aerosolized vasodilators in pulmonary hypertension.

Pulmonary hypertension is a life-threatening disease characterized by an increase in artery pressure and vascular resistance in the pulmonary circulation. A primary form of pulmonary hypertension with unknown causes is to be distinguished from the far more frequent secondary forms based on known pulmonary and extrapulmonary disorders. An imbalance in the synthesis of vasoconstrictive and vasodilative agents seems to play an important role in the etiology of pulmonary hypertension. This pathophysiological background offers the possibility to develop treatment strategies, including application of vasodilative drugs. The intravenous administration of vasodilative agents, however, lacks pulmonary selectivity leading to systemic side effects. Therefore, the application of aerosol techniques for alveolar deposition of vasodilatory drugs was proposed and several studies with inhaled iloprost, a stable prostacyclin analogue, demonstrated preferential vasorelaxation in the pulmonary circulation, with the maximum pulmonary vasodilatory potency corresponding to that of intravenous prostacyclin. Clinical experiences with long-term inhaled iloprost are available showing sustained effects on exercise capacity and pulmonary hemodynamics in patients with pulmonary hypertension. Due to the necessary frequent inhalations (up to 12 times a day) and the potency of the prostaglandins, the choice of the nebulizer is critical, requiring physical characterization and device comparison studies under the right heart-catheter conditions. The concept of aerosolized vasodilators is meanwhile well established and offers a promising perspective in the treatment of pulmonary hypertension.     

Deposition Patterns of Aerosolized Drugs Within Human Lungs: Effects of Ventilatory Parameters

A mathematical model for inhaled aerosolized drugs is validated by comparisons of predicted particle deposition values with experimental data from adult subject inhalation exposure tests. The model is subsequently used to study the effects of ventilatory parameters on particle deposition patterns within the human lung. By altering breathing profiles, deposition values can be affected regarding quantity delivered and spatial location. Increased tidal volumes and breath-holding times increase deposition in the pulmonary region, while increased inspiratory flow rates increase deposition in the tracheobronchial region. Based upon fluid dynamics considerations (Reynolds numbers), an original method of partitioning the lung is also presented. The model has implications with regard to aerosol therapy, indicating that the efficacies of inhaled pharmacological drugs in the prophylaxis and treatment of airway diseases can be improved by regulating breathing profiles to deposit particles selectively at prescribed sites within the lung.