YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
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Symposium Reviews
  • Masayoshi Hirohara, Kazushige Ijuin
    2020 Volume 140 Issue 7 Pages 839-840
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS
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  • Masahiko Kimura
    2020 Volume 140 Issue 7 Pages 841-850
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    In October 2015, the Ministry of Health, Labour and Welfare of Japan newly included “health support functions” and “advanced pharmaceutical control functions” as part of “primary-care pharmacy” in the pharmacy vision for patients. “Health support functions” were defined as recommending that patients seek medical consultations, introducing them to relevant medical institutions, and contributing to disease prevention and health support among local residents, apart from health counseling and the consolidation of a framework for the appropriate selection and supply of and advice on pharmacist-only over-the-counter medications, etc. On the other hand, the term “advanced pharmaceutical control functions” is presumed to imply meeting the needs for advanced pharmaceutical control, e.g., cooperation with specialized medical institutions in addressing adverse reactions caused by anticancer drugs and support of the selection of anti-HIV drugs. However, the details remain unknown. Since the opening of the Akebono pharmacy group 22 years ago, our staff members have visited home-care patients, controlled and guided the use of pharmaceuticals, and supported all types of home-care patients including those with end-stage cancer and amyotrophic lateral sclerosis, undergoing home parenteral nutrition, and pediatric home-care patients. We have experienced many cases requiring sophisticated pharmaceutical control, e.g., pain control with opioids, sterile preparation of transfusions, and supply of special medical devices. We would like to consider the requirements for pharmacy-provided home healthcare that depends heavily on medical treatment as one advanced pharmaceutical control function.

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  • Takeya Shiraishi
    2020 Volume 140 Issue 7 Pages 851-858
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    In preparation for the advent of a super-aged society in 2025, it is urgent to establish local comprehensive care systems appropriate to the characteristics of the area, so that people can live out their lives as they choose in their own homes. As we move toward a society in which many people are aging and dying at the same time, it is clear that pharmacists will increasingly attend home-care patients during their final days. Our pharmacy had 295 approved home-care patients over the 10 years from 2007 to 2017, of whom 64% (189) had cancer and 36% (106) had other illnesses. Many patient requests were for intravenous nourishment and pain management injections, and the period of home care for 51.7% of end-stage cancer patients was 30 d or less. In this situation, in cases where medical dependence, including at-home palliative care is high, it is essential to begin preparing an environment suited to the patient's personality, medical and nursing needs, and financial situation by asking them how they want to live their lives while they are still in hospital. In order to provide constant at-home palliative care to patients, it is critical for pharmacists to encourage interprofessional relations, including healthcare, nursing care, and welfare. We report the current situation and challenges with respect to interprofessional work and the roles of community pharmacists in a home-care setting.

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  • Michiyo Kawana
    2020 Volume 140 Issue 7 Pages 859-867
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    Our pharmacy is a support center for home-care dispensing with a sterile dispensary, actively participating in a regional collaboration among medical treatment, nursing, and social care. We have supported hundreds of home-care patients, most of whom were elderly people living at home but a dozen or so were pediatric patients. Although the primary diseases of the children varied, what they had in common was a high degree of medical dependence and it was difficult to move them. At the same time, a caregiver had to be in constant attendance because medical care was intermittent. At the pharmacy, they faced long waiting times and received so many medications that they needed platform carts to carry them. By providing pharmacist-led home guidance on medications, we supported the pharmacotherapy of children with extreme symptoms who remained under the supervision of a physician from an advanced medical institution even after returning home. Through my experience of visiting both elderly people and children, it is clear that the home medical care system for the elderly, which assumes that the patients' physicians will visit their homes, is badly suited to pediatric patients who must visit advanced medical institutions for examinations.

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  • Eri Sakuma, Junya Kawauchi, Yasuaki Gyoda, Yukie Oikawa, Junko Watanab ...
    2020 Volume 140 Issue 7 Pages 869-875
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    In recent years, home medical care has been strongly promoted. As a consequence, the conditions managed in home medical care have become increasingly diverse. Heart failure is one of the most common disorders after malignant diseases. Patients with chronic heart failure (CHF) are often forced into hospitalization because of the inability to control symptoms with oral medications, even though they hope to stay at home. Recently, we have experienced a case where the patient required continuous administration of dobutamine at home. In order to carry out CHF care at home successfully, it is necessary to adjust the doses of catecholamine and furosemide swiftly in response to changes in patients' conditions. In this case, the patient was able to spend four months at home thanks to the cooperation of a team of a physician, nurses, and pharmacists. Catecholamine-dependent patients with terminal CHF require expensive medical infusion pumps for precise administration. However, the economic assistance to such patients remains insufficient. Furthermore, dobutamine and furosemide injections are not dispensed extramurally, and therefore might become an impediment to the cooperation of the team. In this symposium, I consider and discuss the role of pharmacists in a home medical care team for patients with terminal CHF.

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  • Kazuki Kushida, Masayoshi Hirohara
    2020 Volume 140 Issue 7 Pages 877-884
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    In 1994, community pharmacists first started patient-visiting services under health insurance coverage. There are a wide variety of home-care patients for whom pharmacists provide care. They include elderly patients with chronic disease, pediatric home-care patients with or without special needs, patients with dementia, cancer patients receiving palliative care, and others. Pharmacies engaging in home pharmaceutical care should establish an adequate system in terms of the following aspects: 1) number of pharmacists; 2) availability of a sterile dispensing room; 3) stock of medical narcotics; and 4) stock of medical supplies. Nevertheless, it is impossible for every pharmacy to provide home pharmaceutical care in the same fashion, since many factors, such as the vision of the pharmacy proprietor, business size, experience and expertise of pharmacists, and regional characteristics vary. A survey of 149 pharmacies authorized to dispense injection drugs in Tokyo clarified the profile of pharmacies specializing in home pharmaceutical care based on the number of patients served, number of patients receiving at-home end-of-life care, amount of medical narcotics in stock, etc. The results revealed that specialized pharmacies were required by home-care patients who were highly dependent on medical treatment. In the future, as the number of home-care patients with high medical treatment dependence is expected to continue rising, an evaluation of pharmacies meeting the needs of these patients should be undertaken from the viewpoint of advanced pharmaceutical management functions.

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  • Teruo Kuroda, Atsushi Matsuzawa, Shusuke Kuge
    2020 Volume 140 Issue 7 Pages 885
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS
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  • Kiyoshi Kita
    2020 Volume 140 Issue 7 Pages 887-894
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    In developed countries, it is said that “threats of infectious diseases are already thought as things of the past”. However, as you can see in the case of Ebola hemorrhagic fever that occurred in West Africa, this is a big mistake. Among infectious diseases, only smallpox has been successfully eradicated worldwide. In addition to the three major infectious diseases of HIV/AIDS, tuberculosis, and malaria, there is another group called emerging and reemerging infectious diseases. Recently, neglected tropical diseases (NTDs) have been listed as threats by the WHO, as have drug-resistant bacteria. The spread of these pathogens is increasing due to an increase in global travel. Malaria and more than half of the NTDs are parasitic diseases, such as trypanosomiasis and soil-borne helminthiasis. These are caused by parasites, with eukaryotes similar to their host mammals. In the case of these NTDs, protective immune responses induced by differences between a pathogen and host do not work well, and there is no vaccine against parasites. As for drugs developed to treat these diseases, because the properties of enzymes and target receptors are very similar, and effective drugs simultaneously show efficacy against both the disease and the host, severe side effects often occur. Therefore, the search for targets specifically present in parasites, and screening for drugs that inhibit their physiological functions, is extremely important. Here, as an example of the development of antiparasitic drugs, I will introduce a study on malaria.

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  • Masayuki Saijo
    2020 Volume 140 Issue 7 Pages 895-899
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    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.

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  • Kazunori Oishi, Hiroshi Satoh, Keiko Tanaka-Taya
    2020 Volume 140 Issue 7 Pages 901-904
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    Although rubella is usually a mild, febrile illness, and up to 50% of rubella infections are asymptomatic, congenital rubella syndrome (CRS) can occur in the developing fetus of a pregnant woman infected with rubella virus (RV) in early pregnancy. After a rubella outbreak from early 2012 to late 2013 in Japan, another outbreak re-emerged from mid-2018 in the Tokyo metropolitan area and other large cities. In 2018, and up to epidemiological week (EW) 25 in 2019, more than 4000 rubella cases had been reported. Three CRS cases were also reported up to EW 24. Seroepidemiological surveys among Japanese residents indicated that the susceptible pocket to RV in male adults aged 30-50 years, as determined in 2013, remained unchanged in 2018. To reduce the number of male adults sensitive to RV, in early 2019, Japan's Ministry of Health, Labour and Welfare decided to implement routine immunization of male adults aged 40-57 years between 2019 and 2021. These male adults have been determined to have low anti-RV antibodies, and were therefore designated as the target population for this routine immunization (as category A). Although one-third of male patients with rubella reported in 2018 were in their 20 s and 30 s, these younger generations were not included in the target population for routine immunization against rubella, because they had already received a routine vaccination. Rubella vaccination is also required for male adults aged 20-40 years to diminish the susceptible pocket.

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  • Hajime Nakai
    2020 Volume 140 Issue 7 Pages 905-908
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    The rate of detection of various resistant bacteria has recently increased, though the development of antimicrobial agents has been delayed. In the hospital setting, an antimicrobial stewardship team (AST) works to assure that resistant bacteria do not appear, while an infection control team (ICT) works to assure these resistant bacteria do not spread. Additionally, ICT and AST work together on the appropriate use of antimicrobial agents. In order to combat infectious diseases regionally, it will be important for hospitals and pharmacies to share such information as infection control, consumption trends of each antimicrobial agent, and the susceptibility rate of antimicrobial agents. In addition, cooperation between hospitals and community pharmacies is important to assure patients can receive appropriate medical treatment after leaving the hospital. It is essential to have a common understanding of the prevalent infectious disease in order to continuously provide safe and effective drug treatment in the region. Therefore, we propose educating health care professionals about the proper use of antimicrobial drugs through cooperation between hospitals and community pharmacies. In this symposium, we will introduce those infectious control activities a pharmacist will focus on, as well as the proper use of antimicrobial agents, and regional cooperation activities.

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  • Shigeru Fujimura
    2020 Volume 140 Issue 7 Pages 909-912
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    In medical care, qualified physicians, nurses, and pharmacists have come to be recognized as a team integral to a patient's success, and this team approach to medical care has become popular. In the infectious disease field, more hospitals are practicing antimicrobial stewardship as a team, in addition to the conventional infection control team (ICT). As a result, infectious disease chemotherapy pharmacists are in demand. However, this specific qualification is hard to acquire for pharmacists working in a primary care pharmacy. The problem of multidrug-resistant bacteria is of vital interest today. The National Action Plan on Antimicrobial Resistance 2016-2020, published in Japan, includes an aim to largely reduce the consumption of each oral antimicrobial agent, in order to control the emergence of resistant bacteria. Hospitals and primary care pharmacies will achieve this aim differently. For infection control by primary care pharmacies, the emergence control of a resistant bacteria is important, as is the control of outbreak in a region.

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Regular Articles
  • Toshiaki Hatanaka, Yasuo Yoshihashi, Masataka Ito, Katsuhide Terada, E ...
    2020 Volume 140 Issue 7 Pages 913-921
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS
    Supplementary material

    Controlling the physicochemical properties of a drug formulation is important for proper drug efficacy, since in the gastrointestinal tract many drugs undergo dissolution, limiting their efficacy. Factors affecting a drug's physicochemical properties include its crystal habit. Therefore, we predicted the crystal habit by molecular simulation for the purpose of controlling crystal morphology. In this study, we used aspirin as a model compound. By performing simulations based on known crystal structure data, we trained the simulation algorithm to produce the cubic and plate-like morphologies of crystals actually obtained. By these methods, we showed that the crystal plane of the crystal form actually obtained coincides with the characteristic crystal plane obtained by simulation. Furthermore, to consider the influence of the crystallization solvent on crystal growth, we simulated adsorption of solvent molecules on characteristic crystal planes. The difference in adsorption energy of the solvent molecules prevents the aspirin molecules from attaching to the crystal plane. As a result, we concluded that the crystal habit was caused by the difference in growth rate of the crystal plane. By applying the methods developed in this research, the growth of crystal planes can be predicted by molecular simulation, making it possible to efficiently obtain crystal forms with optimal physical properties for drug development. We believe that further development of this approach will lead to dramatic decreases in the cost and duration of drug development.

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  • Chihiro Kawano, Yurika Isozaki, Ayumi Nakagawa, Takeshi Hirayama, Kazu ...
    2020 Volume 140 Issue 7 Pages 923-928
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    Riluzole, a drug used in the management of amyotrophic lateral sclerosis (ALS), is associated with a high incidence of liver failure. It is imperative to determine risk factors and severity of liver injury in patients taking riluzole to devise an appropriate treatment regimen. We, therefore, studied risk factors for liver injury in ALS patients who were prescribed riluzole at Kitasato University East Hospital from 1999 to 2015. Of the 222 patients enrolled in this study, 113 and 109 patients were diagnosed with mild to moderate (grade 1 or 2) and without (grade 0) liver injury, respectively. Prediction of risk factors was determined using binary logistical regression analyses. The results showed that 50.9% (n=113) of ALS patients developed mild to moderate liver injury; 71.7% and 53.1% of patients were concurrently using CYP1A2 inhibitors (p=0.005) and diclofenac (p=0.032), respectively; 55.8% of patients with liver injury had a history of smoking (p=0.011). Multivariate analyses revealed that the concurrent use of CYP1A2 inhibitors [odds ratio (OR) 2.152, 95% confidence interval (CI) 1.225-3.780, p=0.008] and history of smoking (OR 1.938, 95% CI 1.125-3.340, p=0.017) were independent risk factors for liver injury in patients receiving riluzole. In conclusion, treatment of ALS patients with riluzole, smoking habits, and concurrent use of CYP1A2 inhibitors are independent liver injury risk factors. Further studies on liver injury are warranted in ALS patients treated with riluzole to comprehensively understand the underlying mechanisms of riluzole-associated liver toxicity.

    Editor’s picks

    Riluzole is a drug used to manage amyotrophic lateral sclerosis (ALS). Previous reports indicate a high incidence of liver injury in patients taking riluzole. Therefore, this study aimed to determine the risk factors for liver injury among patients who were prescribed riluzole from 1999 to 2015. As a result, concurrent use of CYP1A2 inhibitors, and history of smoking are independent risk factors associated with the development of liver injury in ALS patients who are prescribed riluzole.

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Notes
  • Takenori Ichimura, Shuichi Nawata, Daisuke Ichikura, Kaoru Murakami, M ...
    2020 Volume 140 Issue 7 Pages 929-936
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    Cisplatin therapy induces kidney injury as a side effect. Thus, replacement fluid must be administered to prevent kidney injury. In our hospital, we use a Gemcitabine and Cisplatin combination chemotherapy (GC) at a total volume of approximately 500 mL for biliary tract cancer. We investigated the safety of GC with a small amount of replacement fluid. As a result, no serious adverse events and renal injury occurred that required discontinuation of treatment. The median overall survival time was 260 d (95% confidence interval, 154-367 d). This study suggests that GC with a small amount of replacement fluid could be performed tolerability. But we need to be careful about choosing patients such as patients who can drink 1 L orally and patients who can be treated as outpatients.

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  • Junji Sakurai, Shinsuke Satoh, Miori Hase, Tomoko Takahashi, Fumiyoshi ...
    2020 Volume 140 Issue 7 Pages 937-941
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    Studies on the drug saxagliptin (marketed in Japan since 2013) suggest favorable efficacy in hemodialysis patients, but included small sample sizes. Noting that some hemodialysis patients at our medical institution had been switched to saxagliptin 2.5 mg from treatment with other dipeptidyl peptidase-4 inhibitors, we decided to evaluate the effects of switching to saxagliptin on blood glucose control in these patients. The study included 11 patients. Before switching drugs, six of the patients used teneligliptin 20 mg and five used linagliptin 5 mg. Mean glycated albumin (GA) from before to 4 months after switching tended to increase in the previous users of teneligliptin 20 mg (18.4±3.0% to 19.5±2.7%) and tended to decrease in the previous users of linagliptin 5 mg (18.8±3.3% to 17.7±1.4%). Lack of a substantial change in GA when the previous users of teneligliptin 20 mg and linagliptin 5 mg were switched to saxagliptin 2.5 mg indicates that these three agents might have comparable antihyperglycemic profiles when used in patients on hemodialysis. Future research following from this pilot study must evaluate the risk of cardiac failure and incidences of adverse events in a larger population, to investigate the long-term efficacy and safety of switching to saxagliptin.

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  • Satoru Mitsuboshi, Hitoshi Yamada, Shuji Yamazaki, Mariko Kobayashi, K ...
    2020 Volume 140 Issue 7 Pages 943-947
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    Concomitant therapy with acetaminophen (APAP) and low-dose aspirin is often used in clinical settings; however, it is unclear whether this combination is involved in the progression of chronic kidney disease (CKD). We hypothesized that concomitant therapy with APAP and low-dose aspirin may cause CKD progression. We carried out a retrospective 6-year cohort study that included all patients who received low-dose aspirin from January 2011 to December 2016 at Kaetsu Hospital. Primary outcome was defined as CKD progression at the end of the study compared with baseline. Among the 441 patients treated during the study period, we identified 89 cases of CKD progression. Multivariate regression analysis showed that exposure to APAP>50 g [odds ratio (OR), 2.68, 95% confidence interval (CI), 1.08-6.70], age increase by 1 year (OR, 1.05, 95% CI, 1.02-1.08), and diabetes mellitus (OR, 2.40, 95% CI, 1.41-4.08) had positive associations with CKD progression. Our findings suggested that concomitant therapy with APAP and low-dose aspirin increased the risk of CKD progression. Therefore, we recommend more thorough monitoring of serum creatinine when patients are on such concomitant therapy. Moreover, it is important to advise users of low-dose aspirin to avoid unnecessary use of APAP, in order to reduce the risk of CKD progression.

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Case Report
  • Daisuke Yamamoto, Tomoo Itoh, Junko Suzuki
    2020 Volume 140 Issue 7 Pages 949-953
    Published: July 01, 2020
    Released: July 01, 2020
    JOURNALS FREE ACCESS

    To contribute to research on the effective practice of pharmaceutical law, we analyzed the learner characteristics that influence learning outcomes in this field at Kitasato University School of Pharmacy. Specifically, we conducted a forced entry multiple regression analysis. The explanatory variables were the learner's gender, course, university entrance examination format, course year progression, completion of related subjects, and submission of class quizzes, while examination performance in pharmaceutical law was the response variable. The learners' course of study and submission of class quizzes were found to have a significant influence on the examination results. The examination performance of students enrolled in a four-year course was 14.4% lower than students enrolled in a six-year course, while students with records of not submitting the class quizzes scored 8.4% lower than those who submitted all the quizzes. It is probable that there was a fundamental difference between the academic ability of the students enrolled in the two courses that affected the examination results. The fact that the submission of class quizzes had an effect on the examination results may be useful in developing a learning guide for the students. To further enhance the evidence of the analysis of learner characteristics in this field, obtaining the results of joint research with other universities is necessary.

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