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      The successful treatment of hypercapnic respiratory failure with oral modafinil

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          Abstract

          Hypercapnic respiratory failure is common in advanced chronic obstructive pulmonary disease and is usually treated by nasal ventilation. Not all patients requiring such ventilation can tolerate it, with anxiety and phobia influencing their reaction, along with treatment failure. We report the case histories of six patients with hypercapnic respiratory failure who were at risk of death due to refusal of nasal ventilation or its failure despite ongoing treatment. We report their improvement with oral modafinil 200 mg tablets used as a respiratory stimulant, which led to discharge, improved arterial blood gases, and offset further admissions with hypercapnic respiratory failure. This drug is licensed for narcolepsy and is said to stimulate the respiratory system via the central nervous system. Its use in respiratory failure is an unlicensed indication, and there are no case reports or studies of such use in the literature. Its respiratory stimulant effects appear better than those with protriptyline, which was a drug previously used until its production was discontinued. Our findings suggest that a study of modafinil in hypercapnic respiratory failure would be warranted, especially for patients with treatment failure or intolerance to nasal ventilation. This may offer a way of shortening hospital stay, improving outcome and quality of life, and reducing death and readmissions.

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          Most cited references 33

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          The NCGC pharmaceutical collection: a comprehensive resource of clinically approved drugs enabling repurposing and chemical genomics.

          Small-molecule compounds approved for use as drugs may be "repurposed" for new indications and studied to determine the mechanisms of their beneficial and adverse effects. A comprehensive collection of all small-molecule drugs approved for human use would be invaluable for systematic repurposing across human diseases, particularly for rare and neglected diseases, for which the cost and time required for development of a new chemical entity are often prohibitive. Previous efforts to build such a comprehensive collection have been limited by the complexities, redundancies, and semantic inconsistencies of drug naming within and among regulatory agencies worldwide; a lack of clear conceptualization of what constitutes a drug; and a lack of access to physical samples. We report here the creation of a definitive, complete, and nonredundant list of all approved molecular entities as a freely available electronic resource and a physical collection of small molecules amenable to high-throughput screening.
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            Thalidomide for treatment of multiple myeloma: 10 years later.

            Thalidomide, bortezomib, and lenalidomide have recently changed the treatment paradigm of myeloma. In young, newly diagnosed patients, the combination of thalidomide and dexamethasone has been widely used as induction treatment before autologous stem cell transplantation (ASCT). In 2 randomized studies, consolidation or maintenance with low-dose thalidomide has extended both progression-free and overall survival in patients who underwent ASCT at diagnosis. In elderly, newly diagnosed patients, 3 independent randomized studies have reported that the oral combination of melphalan and prednisone plus thalidomide (MPT) is better than the standard melphalan and prednisone (MP). These studies have shown better progression-free survival, and 2 have shown improved overall survival for patients assigned to MPT. In refractory-relapsed disease, combinations including thalidomide with dexamethasone, melphalan, doxorubicin, or cyclophosphamide have been extensively investigated. The risks of side effects are greater when thalidomide is used in combination with other drugs. Thromboembolism and peripheral neuropathy are the major concern. The introduction of anticoagulant prophylaxis has reduced the rate of thromboembolism to less than 10%. Immediate thalidomide dose reduction or discontinuation when paresthesia is complicated by pain or motor deficit has decreased the severity of neuropathy. Future studies will define the most effective or the best sequence of combinations which could improve life expectancy.
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              Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. US Modafinil in Narcolepsy Multicenter Study Group.

               M Khan (1997)
              Narcolepsy is a central nervous system disorder characterized by excessive daytime sleepiness and cataplexy. This placebo-controlled, double-blind, randomized, parallel-group, 18-center study assessed the efficacy and safety of modafinil, a new wake-promoting drug for treating sleepiness in narcolepsy. Subjects with narcolepsy (n = 283) received daily modafinil, 200 or 400 mg, or placebo, for 9 weeks, followed by an open-label treatment period. Subjective sleepiness was measured with the Epworth Sleepiness Scale. Objective sleepiness was assessed with the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. Level of illness was measured with the Clinical Global Impression of Change. Modafinil significantly reduced all measures of sleepiness and was associated with significant improvements in level of illness. Medication-related adverse experiences were few, dose-dependent, and mostly rated mild to moderate. Modafinil taken once daily was a very well tolerated and effective wake-promoting agent in the treatment of excessive daytime somnolence associated with narcolepsy. Modafinil demonstrated an excellent safety profile for up to 40 weeks of open-label treatment and efficacy was maintained, suggesting that tolerance will not develop with long-term use. Modafinil is a pharmacologically and clinically promising compound for the treatment of pathological daytime somnolence.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2014
                30 April 2014
                : 9
                : 413-419
                Affiliations
                [1 ]Respiratory Department, St Helier Hospital, Carshalton, Surrey, UK
                [2 ]Pharmacy Department, St Helier Hospital, Carshalton, Surrey, UK
                Author notes
                Correspondence: Veronica Varney, Respiratory Department, St Helier Hospital, Wrythe Lane, Carshalton, Surrey SM5 1AA, UK, Tel +44 208 296 2401, Fax +44 208 296 3163, Email veronica.varney@ 123456esth.nhs.uk
                Article
                copd-9-413
                10.2147/COPD.S54507
                4010627
                24812505
                © 2014 Parnell et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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