著者

篠崎 幸喜

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.132, no.2, pp.237-241, 2012 (Released:2012-02-01)

参考文献数

31

被引用文献数

2 6

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We used a mobile electrocardiograph to manage the adverse effects and interactions of drugs, especially QT-prolonging drugs, in a community pharmacy setting. We report the case of a patient in whom the risk of drug-induced torsades de pointes (TdP) was lowered, after monitoring by community pharmacists. Case: An 80-year-old woman was under donepezil (5 mg/d) therapy for Alzheimer's disease and also taking other drugs that interact with donepezil, namely, benidipine (8 mg/d) and atorvastatin (10 mg/d). The patient was visited almost every month, and an electrocardiogram was usually obtained. QTc prolongation (avg. 470±9 ms) was observed in the first to third tests. Her doctor was informed about these results and the risk factors (advanced age, gender, and drugs interactions (benidipine and atorvastatin)) associated with TdP and asked to respond promptly since several cases of donepezil-induced TdP have been reported. As a result, benidipine was replaced with amlodipine, while the remaining drugs were continued. After the change, a significant decrease in QTc values were observed in the fourth to seventh tests (avg. 441±9 ms, p=0.010), thereby indicating a decrease in TdP risk. The Drug Interaction Probability Scale (object drug, donepezil; precipitant drug, benidipine) score was +6 (probable). Thus, QTc shortening was a result of differences in donepezil-benidipine and donepezil-amlodipine interactions.

著者

秋田 英万 濱 進 水口 裕之 原島 秀吉

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.126, no.11, pp.1047-1057, 2006-11-01 (Released:2006-11-01)

参考文献数

53

被引用文献数

1 1

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For the development of efficient gene vector, intracellular processes such as cellular uptake, endosomal release and nuclear delivery must be overcome. Viruses have also evolved and have developed sophisticated mechanisms for controlling intracellular trafficking for the efficient delivery of their genomes to nuclei in host cells for symbiosis. In the light of these mechanisms, various kinds of artificial devices have been developed to overcome the intracellular barriers. However, in the majority of studies, variation of the transfection activity before and after the modification of devices was evaluated, and intracellular trafficking remained unclear. Therefore, it is understand to recognize which of the intracellular barrier should be intensively improved to enhance the transfection activity. To clarify the rate-limited process in the current non-viral vector, we compared the intracellular trafficking between adenovirus and LipofectAMINE PLUS. As a result, we found that difference of the transfection efficiency between adenovirus and LipofectAMINE PLUS was dominantly derived from the differences on transcription activity. Therefore it is essential to consider the regulation of the intranuclear events to improve the transfection activity of artificial vector.

著者

吉田 和佳奈 齋藤 栄 酒向 孫市 野田 政充 川口 諭 新井 一也 安齋 沙織 久保田 聡 渋谷 清 町田 充 堀野 忠夫 青木 学一 尾鳥 勝也

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.142, no.8, pp.893-900, 2022-08-01 (Released:2022-08-01)

参考文献数

12

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“Leukerin® powder 10%” containing mercaptopurine (6-MP) is an oral anticancer drug that requires careful handling. As a powder formulation, there are risks of exposure due to scattering during dispensing and possible 6-MP contamination to other drugs due to adhesion to the packaging machine. We previously reported that wiping with an alcohol-containing towel is useful for removing scattered powder after dispensing. However, it is recommended to wipe disk-type powder-packaging machines with water instead of cleaning with the alcohol-containing towel. Hence, we scattered 6-MP powder 100 mg (total amount of 6-MP: 10 mg), and then wiped with water three times using different types of cloth each time. We confirmed that third time wiping cloth did not have any 6-MP. Furthermore, we confirmed that the adhering 6-MP could be removed by wipe-cleaning (water-wiping twice and dry-wiping once) after dispensing 6-MP powder at two pharmacies that routinely dispensed 6-MP powder using a disk-type powder-packaging machine. In addition, we confirmed the adhesion of 6-MP in parts of the machine not cleaned by wipe-cleaning and also in parts that were washed only with water, in both the pharmacies. Based on the above observations, we recommend the following steps for cleaning disk-type powder-packaging machines after dispensing 6-MP powder: (1) wipe-cleaning that includes water-wiping twice and then dry-wiping once, (2) cleaning all areas of the packaging machine, and (3) wipe-cleaning with water before washing with water.

著者

清水 雅之

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.142, no.2, pp.115-121, 2022-02-01 (Released:2022-02-01)

参考文献数

6

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Anti-doping (AD) education for athletes is mainly one-way and through passively attended lectures. As such, learning about prohibited substances and highly technical doping rules is often difficult for athletes. Therefore, having athletes passively attending lectures is not enough to prevent unintentional doping violations caused by medicines and supplements. Therefore, it is important for athletes to acquire knowledge about individual prohibited substances as well as active learning and practical knowledge about AD measures. “Doping Guardian” is an educational card game that has been developed to help prevent unintentional doping violations. Participants (pharmacists) of this game can learn how to use medicines and supplements from an AD perspective while simulating the life of an athlete. This presentation will provide an overview of this card game and how it has been used to date.

著者

熊谷 岳文 木平 孝高 藤村 よしの 宮後 憲 片山 千亜季 松谷 望 井上 裕文 鶴田 泰人 吉富 博則 佐藤 英治

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.140, no.4, pp.577-584, 2020-04-01 (Released:2020-04-01)

参考文献数

12

被引用文献数

1 2

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Elneopa NF No. 1 and No. 2 infusions are complete parenteral nutrition solutions packaged as four-chambered bags. They have been used for home parenteral nutrition, with insulin injected into the bags for patients whose blood glucose becomes elevated. In this study, the stability of insulin in No. 1 and No. 2 bags was investigated. The quantity of insulin in Elneopa NF No. 2 was significantly lower than that in Elneopa NF No. 1. When insulin was injected into the upper chamber of either product, decreases in insulin levels were not observed. In contrast, the levels of insulin injected into the lower chamber of both products significantly decreased, with a larger difference in Elneopa NF No. 2. As the amino acid content is different between No. 1 and No. 2, amino acids may be considered a potential cause for the degradation of insulin in the bags. In addition, decreases in insulin levels were observed as the solutions passed through infusion sets just after flushing began, with both Elneopa NF No. 1 and No. 2. In conclusion, the concentration of insulin injected into the Elneopa infusion bags decreases, especially in No. 2 bags, and insulin is absorbed by the infusion sets.

著者

石井 勇太 中川 直人 小原 拓 大原 宏司 栗田 幸代 村井 ユリ子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.140, no.9, pp.1195-1198, 2020-09-01 (Released:2020-09-01)

参考文献数

10

被引用文献数

2

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The purpose of this study is to understand the reading habits of Japanese pharmacists regarding clinical trial literature in 2014. Questionnaires were mailed to 1997 pharmacists in Miyagi Prefecture. Six hundreds and five [342 (56.5%) hospital pharmacists and 254 (42.0%) community pharmacists] responded to questionnaires (Response rate: 30.3%). Regarding the question, “Do you habitually read clinical trial literature?”, 19.5% of hospital and 8.3% community pharmacists responded “yes”, respectively, which showed both pharmacists are not habitual readers of clinical trial literature. That would be because they did not study critical reading of clinical trial literature at pharmacy schools as well as their work environments to access and retrieve clinical trial literature were limited.

著者

稲田 健

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.1, pp.73-77, 2016 (Released:2016-01-01)

参考文献数

22

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Benzodiazepines (BZs) work by agonising gamma-aminobutyric acid (GABA)-BZ-receptor complex and thereby produce sedation and anti-anxiety effects. BZs are commonly used in several clinical areas as hypnotics or anti-anxiety drugs. However, these drugs once supplied by medical institutions often lead to abuse and dependence. Thus it is important for institutions to supply and manage BZs properly. At Tokyo Women's Medical University Hospital educational activities about proper use of BZs are performed by not only medical doctors but also pharmacists. We coordinate distribution of leaflets and run an educational workshop. As a result of these activities, the number of patients receiving BZ prescriptions was reduced. Performing these activities, pharmacists were required to work for patients, doctors, and nurses; they acquired knowledge about BZs such as action mechanisms, efficacy, adverse effects, problems about co-prescription, and methods of discontinuing BZs, as well as information on coping techniques other than medication. The most important point to attend the patients is to answer their anxieties.

著者

瀬戸 康雄

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.129, no.1, pp.53-69, 2009-01-01 (Released:2009-01-01)

参考文献数

80

被引用文献数

12 17

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Chemical and biological warfare agents (CBWA's) are diverse in nature; volatile acute low-molecular-weight toxic compounds, chemical warfare agents (CWA's, gaseous choking and blood agents, volatile nerve gases and blister agents, nonvolatile vomit agents and lacrymators), biological toxins (nonvolatile low-molecular-weight toxins, proteinous toxins) and microbes (bacteria, viruses, rickettsiae). In the consequence management against chemical and biological terrorism, speedy decontamination of victims, facilities and equipment is required for the minimization of the damage. In the present situation, washing victims and contaminated materials with large volumes of water is the basic way, and additionally hypochlorite salt solution is used for decomposition of CWA's. However, it still remains unsolved how to dispose large volumes of waste water, and the decontamination reagents have serious limitation of high toxicity, despoiling nature against the environments, long finishing time and non-durability in effective decontamination. Namely, the existing decontamination system is not effective, nonspecifically affecting the surrounding non-target materials. Therefore, it is the urgent matter to build up the usable decontamination system surpassing the present technologies. The symposiast presents the on-going joint project of research and development of the novel decontamination system against CBWA's, in the purpose of realizing nontoxic, fast, specific, effective and economical terrorism on-site decontamination. The projects consists of (1) establishment of the decontamination evaluation methods and verification of the existing technologies and adaptation of bacterial organophosphorus hydrolase, (2) development of adsorptive elimination technologies using molecular recognition tools, and (4) development of deactivation technologies using photocatalysis.

著者

炭 昌樹 長谷川 千晶 森井 博朗 星野 伸夫 奥貫 裕美 金本 賢枝 堀江 美弥 岡本 陽香 藪田 直希 松田 雅史 神谷 貴樹 須藤 正朝 増田 恭子 岩下 由梨 松田 佳織 本岡 芳子 平 大樹 森田 真也 寺田 智祐

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.5, pp.715-722, 2018 (Released:2018-05-01)

参考文献数

10

被引用文献数

1

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The importance of community-based care systems has increased due to the highly aging population and diversity of disease. To enhance the cooperation among healthcare professionals in community-based care systems, a two-day on-site training program for community pharmacists based on a multidisciplinary team approach was conducted at the Medical Science Hospital of Shiga University from April 2015 to March 2017. There were two professional courses in this training program: the palliative care course and nutrition support course. Both courses consisted of common pharmaceutical care training as follows: regional cooperation among healthcare professionals, pharmacist's clinical activities in the ward, pressure ulcer care, infection control, and aseptic technique for parenteral solutions. Each course was limited to 2 participants. A questionnaire was given to participants in the training program. Seventy-five pharmacists participated in the training and all of them answered the questionnaire. According to the questionnaire, 86% of participants felt that 2 days was an appropriate term for the training program. Positive answers regarding the content of each program and overall satisfaction were given by 100% and 99% of the participants, respectively. In the categorical classification of free comments regarding the expected change in pharmacy practice after the training, both “support for patients under nutritional treatment” and “cooperation with other medical staff” were answered by 24 participants. These results suggested that the 2-day on-site training for community pharmacists facilitated cooperation among healthcare professionals in the community.

著者

清水 忠 上田 昌宏 豊山 美琴 大森 志保 高垣 伸匡

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.5, pp.655-666, 2018-05-01 (Released:2018-05-01)

参考文献数

30

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Practicing evidence-based medicine (EBM) is likely to gain importance for clinical pharmacists in the relatively near future in Japan. An educational program including research and the critical appraisal of literature was required for pharmacy students as of 2015. We organized a six-month practical EBM course for pharmacy students at Hyogo University of Health Sciences. To evaluate its effectiveness, students took a 10-question test after completing the course. The mean score of six students was 8.33±1.79 points. We also conducted a 1-day practical EBM workshop for pharmacists. Changes in knowledge and skills related to EBM were evaluated based on the responses to 10 questions. Knowledge and skills related to several variables improved significantly after the workshop (6.36 points before versus 9.09 points after the workshop; p=0.023). The results suggested that our EBM educational course is effective in improving EBM-related knowledge and skills of pharmacists and pharmacy students.

著者

大山 勝宏 井上 みち子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.7, pp.1065-1071, 2016 (Released:2016-07-01)

参考文献数

35

被引用文献数

5

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Selective beta-adrenergic drugs are used clinically to treat various diseases. Because of imperfect receptor selectivity, beta-adrenergic drugs cause some adverse drug events by stimulating other adrenergic receptors. To examine the association between selective beta-adrenergic drugs and blood pressure elevation, we reviewed the Japanese Adverse Drug Event Reports (JADERs) submitted to the Japan Pharmaceuticals and Medical Devices Agency. We used the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms extracted from Standardized MedDRA queries for hypertension to identify events related to blood pressure elevation. Spontaneous adverse event reports from April 2004 through May 2015 in JADERs, a data mining algorithm, and the reporting odds ratio (ROR) were used for quantitative signal detection, and assessed by the case/non-case method. Safety signals are considered significant if the ROR estimates and lower bound of the 95% confidence interval (CI) exceed 1. A total of 2021 reports were included in this study. Among the nine drugs examined, significant signals were found, based on the 95%CI for salbutamol (ROR: 9.94, 95%CI: 3.09-31.93) and mirabegron (ROR: 7.52, 95%CI: 4.89-11.55). The results of this study indicate that some selective beta-adrenergic drugs are associated with blood pressure elevation. Considering the frequency of their indications, attention should be paid to their use in elderly patients to avoid adverse events.

著者

恩田 光子 今井 博久 七海 陽子 平野 章光 藤井 真吾 荒川 行生

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.3, pp.519-527, 2015 (Released:2015-03-01)

参考文献数

18

被引用文献数

2 8

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A nationwide survey was conducted to verify relations between the workload of home-visiting service by community pharmacists and outcomes. Data were collected on 5447 patients from 1890 pharmacies. Most (61.9%) pharmacists visited patients' homes twice monthly, spending there a net average of 20.6 work minutes. At the time of the survey, 29.8% of the patients had improvement of adherence compared with at start of home visits; 65.5% had no change, and 1.4% had gotten worse. Similarly, 41.6% had decreased unused medications, 54.4% had no change, and 2.3% had increased. Home-visiting pharmacists found adverse drug events (ADEs) caused by drug administration in 14.4% of their patients. They dealt with 44.2% of these cases by discontinuing administration of the responsible drug, 24.5% by reducing the dosage, and 18.3% by changing drugs, with a total of 88.1% having been improved. Prescription changes intended to correct problems occurred in 37.1% of the patients. In patients whom the pharmacists visited more often, a higher percent had ADEs, had their prescription changed to correct problems, and had improved adherence and unused medications. The average actual work time was longer in patients whose outcomes improved than in those whose outcomes did not. A higher involvement in homecare by pharmacists was found to improve outcomes of drug treatment.

著者

相原 傳 鈴木 猛

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.71, no.11, pp.1323-1324, 1951-11-25 (Released:2010-02-19)

参考文献数

10

被引用文献数

1 2

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The insecticidal action of the pungent principles of Xanthoxylum piperitum DC., sanshoöl-I (N-isobutyl-2, 4, 8-dodecatrieneamide) and sanshoöl-II (N-isobutyl-2, 4, 8, 10-dodecatetraeneamide), was studied under a comparison with that of spilanthol (N-isobutyl-4, 6-decadieneamide), pungent principle of Spilanthes oleraceae Jacq., using Culex pipiens Pallens as the test insect. The results obtained (Table I) showed that all of them were active as insecticides.

著者

本多 玲 松原 佑樹 窪田 剛志 今野 裕史 桐野 豊 岸本 泰司

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

pp.22-00149, (Released:2022-12-27)

参考文献数

19

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Since the early 2000s, Japan has been frequently noted as being the only country among about 20 major countries where the publication of academic papers has stagnated. During this period, there have been major changes especially with regards to the Japanese pharmacy schools, such as the shift to a six-year schooling system and the rapid increase in the number of private pharmacy schools. However, few studies have focused on academic productivity specifically among pharmacy schools. Therefore, this study analyzed the outputs associated with the publication of peer-reviewed scholarly articles in Scopus search engine per faculty member in pharmacy schools nationwide in 2020. Professors, associate professors, and lecturers were considered as faculty members. The average number of papers published per the faculty member was 3.13 for national and public universities and 1.15 for private universities, with a significant difference between these universities. Dividing the pharmacy schools of private universities into schools established after 2003 and schools established before that, the production coefficient of the former was 0.98 and that of the latter was 1.33. Newly established pharmacy schools were thus found to be slightly less productive in terms of published papers than traditional schools. The paper productivity of private university pharmacy schools is stagnant; the increase in the number of private schools that have adopted a six-year schooling system has contributed to large extent to the creation of clinically competent pharmacists, but it has also brought to light concerns related to the decline in basic research capabilities of Japanese pharmaceutical academia.

著者

宇野 勝次

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.2, pp.151-167, 2018-02-01 (Released:2018-02-01)

参考文献数

88

被引用文献数

1

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Three stages of the pathogenic mechanism of drug allergies can be considered: antigen formation, immune reaction and inflammation/disorder reaction. Drugs are thought to form 4 types of antigens: drug only, polymers, drug-carrier conjugates, and metabolite-carrier complexes. Antigens are recognized by B cell receptors and T cell receptors. Helper T cells (Th) are differentiated into four subsets, namely, Th1, Th2, Th17 and regulatory T cells (Treg). Th1 produces interleukin (IL)-2 and interferon (IFN)-γ, and activates macrophages and cytotoxic T cells (Tc). Macrophages induce type IV allergies, and Tc lead to serious type IV allergies. On the other hand, Th2 produces IL-4, IL-5, and IL-6, etc., and activates B cells. B cells produce IgE antibodies, and the IgE antibody affects mast cells and induces type I allergies. Activated eosinophil leads to the chronic state of type I allergy. Diagnostic testing for allergenic drugs is necessary for patients with drug allergies. Because in vivo diagnostic tests for allergenic drugs are associated with a risk and burden to the patient, in vitro allergy tests are recommended to identify allergenic drugs. In allergy tests performed in vitro, cytological tests are more effective than serological tests, and the leukocyte migration test (LMT) presently has the highest efficacy. An LMT-chamber is better than LMT-agarose in terms of usability and sensitivity, and it can detect about 80% of allergenic drugs.

著者

西條 政幸

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.140, no.7, pp.895-899, 2020-07-01 (Released:2020-07-01)

参考文献数

12

被引用文献数

1

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A sporadic but autochthonous dengue fever outbreak occurred in Tokyo in 2014, although the dengue virus is not in general circulation in Japan. Another lethal infectious disease, known as severe fever with thrombocytopenia syndrome (SFTS), was discovered to be endemic to Japan in January 2013. More than 400 patients with SFTS have been reported so far. The fatality rate of SFTS is approximately 30%. Also in 2014, a large outbreak of mosquito-borne Zika virus infections occurred in the South and Central parts of the American continent. Transplacental infection of a fetus with Zika virus occurs when pregnant women are infected. We cannot escape the risk of being infected with these viruses. Thus, preparedness for these emerging and reemerging virus infections is required.

著者

今浦 将治 山谷 武司 上原 望 眞野 匠智 永瀬 怜司 木村 耕二 菅野 浩 山田 安彦

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.137, no.6, pp.767-774, 2017 (Released:2017-06-01)

参考文献数

15

被引用文献数

4

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We evaluated the effects of pharmacist intervention for adverse drug reaction detection and exacerbation avoidance, as well as the severity and outcome of reactions based on analyses of pharmacist involvement in a collaborative approach to medicine. Of 5436 cases with pharmacist involvement, adverse drug reaction prevention was seen in 440, accounting for 8.1%, and exacerbation avoidance in 213, accounting for 3.9%. We concluded that pharmacist involvement contributes to detect adverse drug reactions and avoid exacerbation, and improves pharmacotherapy safety. We also analyzed 131 cases in which the course after intervention was followed. When categorized by adverse drug reaction severity, Grade 1 and 2 were the same at 45.8%, Grade 3 at 8.4%, respectively. Those findings suggested that pharmacist intervention contributes to early detection of an adverse drug reaction. Also, the relationship between clues for detecting adverse drug reactions by a pharmacist and their severity showed that objective evaluations such as clinical laboratory test results, physical assessments and medication history were important for detecting reactions that became more serious. Patients recovered or recovering from an adverse reaction comprised 76.4%, indicating that pharmacist intervention contributed to exacerbation avoidance and improvement. Our findings revealed the effects of pharmacist intervention for adverse drug reaction detection and exacerbation avoidance, and for safety improvement of pharmacotherapy. Additionally, we considered it necessary for the future pharmacist intervention to improve skills of assessing an adverse drug reaction objectively.

著者

鈴木 潤三 日光 晴美 海保 房夫 山口 稽子 和田 浩 鈴木 政雄

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.124, no.8, pp.561-570, 2004 (Released:2004-08-01)

参考文献数

11

被引用文献数

3 2

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Multiple-chemical sensitivity (MCS) patients are presumed to be compelled to lead inconvenient and difficult lives, because unpleasant and multiorgan symptoms are caused by very small amounts of various chemicals in the living environment. Therefore we conducted a questionnaire survey of MCS patients who are members of support groups to elucidate the problems of MCS patients in using medicinal drugs. In this report, we selected 205 persons who stated that they had been “diagnosed with MCS by a physician” or “a physician suspected a diagnosis of MCS” on the questionnaire as the reason they judged themselves to have MCS. The questionnaire results showed that about 60% of MCS patients have difficulty in using medicinal drugs and that the difficulties are more likely to occur in women, in people 40—59 years old, and in patients who developed MCS in reaction to pesticides or medicinal drugs. The prescribed drugs and OTC drugs noted as usable or unusable by patients in the questionnaire were analyzed from the viewpoint of their medicinal constituents. The results indicated that lidocaine is likely to be unusable by MCS patients. In addition, caffeine, aspirin, chlorphenylamine maleate, minocycline hydrochloride, levofloxacin, etc. were also likely to be unusable by MCS patients. Many patients who recorded drugs containing the above-mentioned remedies as unusable had a past history of allergy, suggesting that allergy is involved in the difficulties of MCS patients in using medicinal drugs.

著者

大岡 伸通

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.9, pp.1135-1143, 2018-09-01 (Released:2018-09-01)

参考文献数

28

被引用文献数

6

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Protein knockdown technologies based on small molecules are attracting considerable attention in the pharmaceutical industry as a strategy for novel drug discovery. We and others have developed such compounds, designated as Specific and Nongenetic Inhibitor of Apoptosis Protein (IAP)-dependent Protein Erasers (SNIPERs), proteolysis-targeting chimeras (PROTACs), and Degronimids, which induce selective degradation of target proteins. These compounds contain two different ligands, specific for an ubiquitin E3 ligase and for a target protein, respectively, connected by a linker. SNIPERs, PROTACs, and Degronimids are designed to cross-link E3 ligase and the target protein to induce polyubiquitylation and proteasomal degradation of the target protein within cells. To recruit the von Hippel-Lindau (VHL) E3 ligase complex and the cereblon (CRBN) E3 ligase complex, a VHL inhibitor and a thalidomide derivative have been integrated into PROTAC and Degronimid constructs, respectively. Similarly, an IAP antagonist has been incorporated into SNIPERs to recruit cellular inhibitor of apoptosis protein 1 (cIAP1) or X-linked inhibitor of apoptosis protein (XIAP) E3 ligase. To date, a range of such compounds have been developed, allowing selective degradation of a variety of proteins, including estrogen receptor α (ERα), oncogenic kinase BCR-ABL, and epigenetic regulator bromodomain-containing protein 4 (BRD4). Some compounds have also demonstrated ability to degrade target proteins in vivo, suggesting that this technology is feasible for use in novel drug development.

著者

小野 秀樹 岡村 真彩 福島 章紘

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

pp.18-00022, (Released:2018-06-20)

参考文献数

82

被引用文献数

9

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The anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic system. These pharmacological actions highly overlap those of amantadine, another anti-influenza virus drug authorized in Japan, and ester-type local anesthetics. Moreover, oseltamivir and amantadine can clinically induce similar adverse neuropsychiatric reactions. In the present study, from the database of the Pharmaceuticals and Medical Devices Agency (PMDA), we surveyed 2,576 drugs for which neuropsychiatric side effects similar to those of oseltamivir, amantadine and local anesthetics (abnormal behavior, confusion, consciousness disturbance, convulsion, delirium, delusion, hallucination, myoclonus, tremor) are listed as “clinically significant adverse reactions”, and found 327 that had at least one of these adverse reactions. Other neuraminidase inhibitors (laninamivir, peramivir and zanamivir) did not elicit such adverse reactions. By discussing the pharmacological effects of drugs that elicit these adverse reactions, we propose that the similarity of adverse neuropsychiatric reactions between oseltamivir and amantadine is possibly attributable to their common pharmacological effects.