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Inhaled drug

Anthony G Messina, Michael Wang, Marshall J Ward, Chase C Wilker, Brett B Smith, Daniel P Vezina, Nathan Leon Pace
BACKGROUND: General anaesthesia is usually associated with unconsciousness. 'Awareness' is when patients have postoperative recall of events or experiences during surgery. 'Wakefulness' is when patients become conscious during surgery, but have no postoperative recollection of the period of consciousness. OBJECTIVES: To evaluate the efficacy of two types of anaesthetic interventions in reducing clinically significant awareness:- anaesthetic drug regimens; and- intraoperative anaesthetic depth monitors...
October 18, 2016: Cochrane Database of Systematic Reviews
Jason J Rose, Ling Wang, Qinzi Xu, Charles F McTiernan, Sruti Shiva, Jesus Tejero, Mark T Gladwin
Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1-3%. A significant number of patients who survive CO poisoning suffer from long term neurologic and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels, but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation and free radical generation, especially in the brain and heart...
October 18, 2016: American Journal of Respiratory and Critical Care Medicine
Stephen W Stein, Charles G Thiel
In 1956, Riker Laboratories, Inc., (now 3 M Drug Delivery Systems) introduced the first pressurized metered dose inhaler (MDI). In many respects, the introduction of the MDI marked the beginning of the modern pharmaceutical aerosol industry. The MDI was the first truly portable and convenient inhaler that effectively delivered drug to the lung and quickly gained widespread acceptance. Since 1956, the pharmaceutical aerosol industry has experienced dramatic growth. The signing of the Montreal Protocol in 1987 led to a surge in innovation that resulted in the diversification of inhaler technologies with significantly enhanced delivery efficiency, including modern MDIs, dry powder inhalers, and nebulizer systems...
October 17, 2016: Journal of Aerosol Medicine and Pulmonary Drug Delivery
Kenneth N Olivier, David E Griffith, Gina Eagle, John P McGinnis Ii, Liza Micioni, Keith Liu, Charles L Daley, Kevin L Winthrop, Stephen Ruoss, Doreen J Addrizzo-Harris, Patrick A Flume, Daniel Dorgan, Matthias Salathe, Barbara A Brown-Elliott, Renu Gupta, Richard J Wallace
Rationale Lengthy multi-drug, toxic, and low efficacy regimens limit management of pulmonary nontuberculous mycobacterial (PNTM) disease. Objective This phase 2 study investigated efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory PNTM (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease. Methods During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multi-drug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days...
October 17, 2016: American Journal of Respiratory and Critical Care Medicine
Keiji Ohata, Toyofumi F Chen-Yoshikawa, Toshi Menju, Ei Miyamoto, Satona Tanaka, Mamoru Takahashi, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date
BACKGROUND: Rho-kinase, an intracellular serine/threonine kinase, is a key regulator of cytoskeletal dynamics. Recent studies have demonstrated that Rho-kinase is involved in the ischemia-reperfusion injury (IRI) pathogenesis of many organs; however, its involvement with lung IRI remains unclear. This study assessed the association of Rho-kinase with lung IRI and evaluated the protective effect of inhaled Rho-kinase inhibitors in lung IRI. METHODS: The study included isolated rat lung perfusion models, divided into three groups: sham, Rho-kinase inhibitor, and warm ischemia (n = 6 each)...
October 12, 2016: Annals of Thoracic Surgery
Caroline Anne Mitchell, Alice Pitt, Joe Hulin, Rod Lawson, Fleur Ashby, Ivan Appelqvist, Brigitte Delaney
OBJECTIVES: Increased rates of illicit drug inhalation are thought to expose opiate misusers (OMUs) to an enhanced risk of respiratory health problems. This pilot study aimed to determine the feasibility of undertaking respiratory screening of OMUs in a community clinic. SETTING: Single-centre UK community substance misuse clinic. PARTICIPANTS: All clinic attendees receiving treatment for opiate misuse were eligible to participate. 36 participants (mean age=37) were recruited over a 5-week period...
October 14, 2016: BMJ Open
Alexandre Y Saito, Adriana A Marin Rodriguez, Danielle S Menchaca Vega, Rodrigo A C Sussmann, Emília A Kimura, Alejandro M Katzin
Malaria, an infectious disease that kills more than 438,000 people per year worldwide, is a major public health problem. The emergence of strains resistant to conventional therapeutic agents necessitates the discovery of new drugs. We previously demonstrated that various substances, including terpenes, have antimalarial activity in vitro and in vivo. Nerolidol is a sesquiterpene present as an essential oil in several plants that is used in scented products and has been approved by the US Food and Drug Administration as a food-flavouring agent...
September 30, 2016: International Journal of Antimicrobial Agents
Per Bäckman, Ulrika Tehler, Bo Olsson
BACKGROUND: Exposure following oral inhalation depends on the deposition pattern of the inhaled aerosol, the extent and rate of oral and pulmonary absorption, as well as systemic distribution and clearance. For lipophilic inhaled compounds with low water solubility and high permeability, the extent and rate of pulmonary absorption can be assumed dependent on deposition pattern as well as dissolution rate. MATERIALS AND METHODS: A mechanistic model of airway deposition, mucociliary clearance, dissolution, absorption, and dissipation was applied to simulate systemic exposure of the novel selective glucocorticoid receptor modulator, AZD5423, when dosed to healthy volunteers using two different nebulizers and two different dry powder inhalers in combination with two different primary particle size distributions...
October 14, 2016: Journal of Aerosol Medicine and Pulmonary Drug Delivery
Jeffry Weers, Andy Clark
Current marketed dry powder inhalers utilize the energy from patient inspiration to fluidize and disperse bulk powder agglomerates into respirable particles. Variations in patient inspiratory flow profiles can lead to marked differences in total lung dose (TLD), and ultimately patient outcomes for an inhaled therapeutic. The present review aims to quantitate the flow rate dependence in TLD observed for a number of drug/device combinations using a new metric termed the Q index. With this data in hand, the review explores key attributes in the design of the formulation and device that impact flow rate dependence...
October 13, 2016: Pharmaceutical Research
Vincent Levet, Rémi Rosière, Romain Merlos, Luca Fusaro, Gilles Berger, Karim Amighi, Nathalie Wauthoz
The present study focuses on the development of dry powders for inhalation as adjuvant chemotherapy in lung cancer treatment. Cisplatin was chosen as a potential candidate for a local treatment as it remains the main platinum component used in conventional chemotherapies, despite its high and cumulative systemic toxicities. Bulk cisplatin was reduced to submicron sizes using high-pressure homogenization, mixed with a solubilized lipid and/or PEGylated component and then spray-dried to produce controlled-release dry powder formulations...
October 11, 2016: International Journal of Pharmaceutics
Sylvia Natalie Kłodzińska, Petra Alexandra Priemel, Thomas Rades, Hanne Mørck Nielsen
Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused by Pseudomonas aeruginosa infections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combat P. aeruginosa infections in CF patients are focused mainly on the delivery of antimicrobials to the lower respiratory tract, disregarding the sinuses. However, the sinuses constitute a reservoir for P. aeruginosa growth, leading to re-infection of the lungs, even after clearing an initial lung infection...
October 9, 2016: International Journal of Molecular Sciences
Q Lv
OBJECTIVE: In order to seek an effective strategy for clinical treatment of acute lung injury (ALI), we are committed to explore the effect of combination therapy of glucocorticoid and hyaluronic acid on acute lung injury caused by an endotoxin (LPS) and its mechanism. MATERIALS AND METHODS: Adult male Sprague-Dawley (SD) rats were divided randomly into 5 groups: normal group (n=8); LPS group (n=8); dexamethasone +LPS group (DXMS group, n=8); hyaluronic acid+ LPS group (HA group, n=8); dexamethasone +hyaluronic acid +LPS group (DXMS+HA group, n=8)...
September 2016: European Review for Medical and Pharmacological Sciences
Jadwiga Nędza, Renata Polaniak, Rafał J Bułdak, Milena Majchrzak, Joanna Margasiń-Ska, Marcin Rojkiewicz, Rafał Celiński, Elżbieta Grochowska-Niedworok
Recently, there has been an increase in the consumption of designer drugs, substances aimed at producing psychoactive, energizing, euphoric or anesthetic effects. Designer drugs are substitutes of actual narcotics, whose possession is banned under Polish law according to the Act of 29 July 2005. The latest reports suggest that the number of synthetic psychoactive substances is increasing. In the span of 2012, a total of 28 new synthetic cannabinoids were discovered in member states of the European Union. Synthetic psychoactive substances appear in different forms on the market: tablets (often very colourful and interestingly-shaped), seeds, dried product (sprayed with synthetic substance and redried), crystals or powder...
July 29, 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
Kathirvel Gopalakrishnan, Amar S More, Gary D Hankins, Tatiana N Nanovskaya, Sathish Kumar
Approximately 20% of pregnant women smoke despite intentions to quit. Smoking cessation drugs, such as nicotine replacement therapy (NRT) and bupropion, are recommended treatments. Adverse cardiovascular outcomes in offspring have raised concerns about NRT's safety during pregnancy. However, the effect of bupropion is unknown. Using a rat model, we determined whether NRT and bupropion interventions during pregnancy are safer than continued smoking on offspring's cardiovascular function. Male offspring of controls and dams exposed to cigarette smoke (1...
October 12, 2016: Reproductive Sciences
Michael M Lipp, Richard Batycky, Jerome Moore, Mika Leinonen, Martin I Freed
Inhaled drugs offer advantages, such as rapid onset of action, but require formulations and delivery systems that reproducibly and conveniently administer the drug. CVT-301 is a powder formulation of levodopa delivered by a breath-actuated inhaler that has been developed for treating OFF episodes (motor fluctuations between doses of standard oral levodopa) in patients with Parkinson's disease (PD). We present preclinical, phase 1, and phase 2 results for CVT-301. In dogs insufflated with a levodopa powder, plasma levodopa peaked in all animals 2...
October 12, 2016: Science Translational Medicine
Yen Leong Chua, Ka Hang Liong, Chiung-Hui Huang, Hok Sum Wong, Qian Zhou, Say Siong Ler, Yafang Tang, Chin Pei Low, Hui Yu Koh, I-Chun Kuo, Yongliang Zhang, W S Fred Wong, Hong Yong Peh, Hwee Ying Lim, Moyar Qing Ge, Angela Haczku, Veronique Angeli, Paul A MacAry, Kaw Yan Chua, David M Kemeny
Previous studies have highlighted the importance of lung-draining lymph nodes in the respiratory allergic immune response, whereas the lung parenchymal immune system has been largely neglected. We describe a new in vivo model of respiratory sensitization to Blomia tropicalis, the principal asthma allergen in the tropics, in which the immune response is focused on the lung parenchyma by transfer of Th2 cells from a novel TCR transgenic mouse, specific for the major B. tropicalis allergen Blo t 5, that targets the lung rather than the draining lymph nodes...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Yang Quan-Jun, Zhang Jian-Ping, Zhang Jian-Hua, Han Yong-Long, Xin Bo, Zhang Jing-Xian, Dai Bona, Zhang Yuan, Guo Cheng
Inhaled budesonide and salbutamol represent the most important and frequently used drugs in asthmatic children during acute exacerbation. However, there is still no consensus about their resulting metabolic derangements; thus, the present study was conducted to determine the distinct metabolic profiles of these two drugs. A total of 69 children with asthma during acute exacerbation were included, and their serum and urine were investigated using high-resolution nuclear magnetic resonance (NMR). A metabolomics analysis was performed using a principal component analysis and orthogonal signal correction-partial least squares using SIMCA-P...
October 12, 2016: Basic & Clinical Pharmacology & Toxicology
Anna K Stalder, Dominik Lott, Daniel S Strasser, Hans G Cruz, Andreas Krause, Peter M A Groenen, Jasper Dingemanse
AIMS: The main objectives of these two Phase 1 studies were to investigate safety and tolerability as well as the pharmacokinetic/pharmacodynamic profile of the novel potent and selective FPR2/ALX agonist ACT-389949. A challenge model was used to assess the drug's anti-inflammatory potential with the aim of selecting a dosing regimen for future patient studies. METHODS: Two double-blind, randomized Phase 1 studies investigated safety, tolerability, pharmacokinetics, and pharmacodynamics of ACT-389949 at different doses and dosing regimens...
October 11, 2016: British Journal of Clinical Pharmacology
Haruko Yokoyama, Kanako Ito, Hirokazu Mihashi, Yasuyuki Shiraishi, Risa Takayanagi, Yasuhiko Yamada
The aim of this study was to establish an appropriate inhalation method with a mometasone furoate dry powder inhaler (MF-DPI). Utilizing a tone-based inhalation training device, we investigated the maximum peak inspiratory flow rate time (Tmax PIFR) and peak inspiratory flow rate (PIFR) to determine whether either had an influence on lung deposition with use of an MF-DPI. A low tone indicated a PIFR of 28 L/min and a high tone that of 40 L/min, while 60 L/min was considered to be the standard. We established an inhalation profile in consideration of a human inhalation pattern, in which Tmax PIFR was set at 0...
2016: Biological & Pharmaceutical Bulletin
Ronald Dahl, Alan Kaplan
BACKGROUND: In many countries worldwide, the long-acting anticholinergic drug tiotropium is available as a dry powder formulation delivered by means of the HandiHaler® inhalation device and as an aqueous solution delivered via the Respimat® Soft Mist™ Inhaler. Tiotropium HandiHaler® is a single-dose, dry powder, breath-actuated inhaler that provides delivered doses and lung deposition of tiotropium that are, over a wide range, not influenced by the severity of chronic obstructive pulmonary disease (COPD)...
October 11, 2016: BMC Pulmonary Medicine
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