In Japan, a national countermeasure has been forwarded since the enactment of the Basic Act on Suicide Countermeasures in 2006 and the Comprehensive Suicide Prevention Initiative in 2007. The distinctive policy of the Japanese countermeasure is expressed as the word, “comprehensive,” which means that suicide prevention may not only be carried out only by mental health measures but also by comprehensive measures including chance of administrative practices. This policy is proper, although mental health measures appear to be too simple inclining to psychiatric treatments for the classic type of “depression” by a pharmacotherapy. The authors have insisted that mental health measures including psychiatric treatments are also required to be more comprehensive. This paper describes that benzodiazepine (BZ)-abuse problems including overdosing by suicidal intents have got worse recently as psychiatric clinics have increased and most of BZ abusers obtain the abused drugs form psychiatrists. This current situation indicates that pharmacists need to monitor psychiatrists' prescribing behavior and qualities of psychiatric treatment is required to be refined, suggesting pharmacists may be one of the “Gate Keeper,” as supporting resources for suicide prevention. Additionally, this paper explained that basic attitudes and responses acquired by pharmacists as a supporter for suicide prevention.
The nonmedical use of medications, including psychotropic drugs, is a growing health problem in Japan. According to a nationwide survey of mental hospitals, the proportion of patients with sedative (mainly benzodiazepine)-related disorders has more than doubled over the last decade. An association between psychotropic drug overdose and suicide risk has also been reported. Furthermore, over-the-counter drug abuse is still a serious problem in Japan. In recent years, pharmacists have been expected to act as gatekeepers, making timely identifications of suicide risk or substance abuse and directing these individuals to appropriate medical care facilities. In August 2012, the revised Comprehensive Suicide Measures Act identified pharmacists as one professional group that should act as gatekeepers. This article begins by reviewing the fundamental terms involved in understanding the nonmedical use of medications, including abuse, dependence, and intoxication. The current situation of substance abuse and dependence is then introduced through a summary of several epidemiological surveys conducted in Japan. Finally, the role of pharmacists as gatekeepers in preventing substance abuse and dependence on medications is discussed.
Pharmacists work in places where they often get in contact with people who may have trouble with their illness, patients and patients' family with prescription, and customers who purchase over-the-counter (OTC) drugs and/or daily goods. Pharmacists can also identify excessive or unsuitable use of OTC drugs resulting from a psychiatric disorder. Moreover, they are in a position in which they can also find the normal-dose addictions and fatigued patient's family resulting from their daily patient's care. Since the consultation to a pharmacist is free of charge, many people often go to the pharmacist to talk about their health concerns. If pharmacists can get in contact with persons who are not aware of their mental illness and send them to the primary care physician, the pharmacists may contribute to prevent suicide and find the unrecognized psychiatric disorder. However, since pharmacists have little knowledge regarding to the psychiatric disorder, they cannot actively contact with this type of people. This article will argue about the methodology and education for pharmacists to connect undiagnosed patients to the appropriate medical care. It is proposed that the pharmacists should encourage the undiagnosed psychiatric patients to contact with the primary care physician. In addition, pharmacists should recommend the change of prescription to the medical doctors who examine the patients expected the addiction to the prescribed drug.
Interleukin 1 (IL-1) was initially defined as a factor which is produced by macrophages and exhibits proliferative activity on thymocytes and fibroblasts, B cell activation and endogenous pyrogen activity. Now IL-1 is known to exhibit pleiotropic activities on various cell types and play important roles in the regulation of immune, nervous and endocrine systems, progression of tumor cells, hematopoietic cell proliferation/differentiation and especially in inflammatory diseases. In 1985 I found that IL-1 exhibits cytocidal activity against human melanoma cells. Since then I have been engaged in the research of various aspects of IL-1. This review summarizes current knowledge of IL-1, including our research and beneficial effect of IL-1 blocking on inflammatory diseases.
The Nobel Prize in Chemistry for 2002 was shared by John B. Fenn and Koichi Tanaka “for their development of soft desorption methods for mass spectrometric analyses of biological macromolecules”. Indeed, electrospray ionization and soft laser desorption ionization have proved to be of great value in “omics”, such as metabolomics, transcriptomics and proteomics in providing a systematic and quantitative approach to the study of biological systems and networks. Moreover, these techniques have made great contributions to metabolic studies that are used for development of new drugs, as well as to the diagnosis of diseases including cancer based on the specific and sensitive detection of molecular biomarkers. In this article, we describe our recent results on characterization of bile acid metabolism in hepatobiliary disease as well as measurement of conjugated urinary tetrahydrocorticosteroids for assessment of altered corticoid metabolism in endocrine disease and the metabolic syndrome.
The pharmaceutical effects of non-steroidal anti-inflammatory drugs (NSAIDs) occur through the inhibition of prostaglandin H synthase (PGHS). Prostaglandin H2 is produced from arachidonic acid via peroxidase and cyclooxygenase cycles in PGHS. NSAIDs exhibit different levels of reactivity in these reaction cycles. To prevent the development of side effect while maintaining the beneficial effects of drugs, a therapeutic strategy should be used. A new classification of NSAIDs has been proposed based on reactivity to peroxidase. Class 1 includes the majority of NSAIDs, which react with horseradish peroxidase (HRP) compounds I and II. Also, their drugs exhibit spectral changes induced by PGHS peroxidase and diminished ESR signals of the tyrosyl radical of metmyoglobin. They reduce compounds I and II of HRP and scavenge tyrosyl radicals. The branched chain mechanism by which the porphyrin radical is transferred to the tyrosine residue of the protein might be blocked by these NSAIDs. Class 2 includes salicylic acid derivatives that react only with the porphyrin radical and do not react with HRP compound II (oxoferryl species). Class 3 includes aspirin, nimesulide, tolmetin, and arylpropionic acid derivatives, including ibuprofen and the coxibs such as celecoxib and rofecoxib, which are not substrates for HRP or PGHS peroxidase. It seems that the selectivity of NSAIDs to PGHS1 and PGHS2 depends on their reactivity with cyclooxygenase rather than with the peroxidase of PGHS. The best drug for each inflammatory disease should therefore be selected for therapy.
The text mining and full-text searching function were used to analyze the digitalized daily reports of the practical training in pharmacology submitted to the web system in Fukuyama University. Collocations connected to the word “inspection” were searched in the daily reports using the text mining and the full-text search functions of the system. Many collocation groups connected to “inspection” were found in the daily reports and the greatest number of collocations was associated with “preparation of drugs”. Practical training in narcotic dispensing has two different aspects: inspection and experience training. The number of people who reported a relation between “inspection” and “narcotics dispensing” in the daily reports was very similar to those who reported a connection between “experience” and “narcotics”. Practical training to handle narcotic dispensing is the most fundamental training that the pharmacist must undertake. The progression of team-based medical care has caused medical personnel to recognize the practical training in pharmacology, and the number of the people who reported a relation between “inspection” and “team medical care” in 2011 increased in comparison to 2010. Moreover, the progression of cooperation among hospitals, pharmacies, and local blanches of the Japan Pharmaceutical Association is beneficial to practical training. Practical training in pharmacology is based on the core curriculum, but undergoes periodic modification due to societal circumstances. Therefore, these results suggest that the construction of web system for submitting daily reports is useful for analyzing the daily reports.
We retrospectively evaluated clinical data before therapy to determine the risk factors for severe neutropenia in advanced non-small-cell lung cancer (NSCLC) patients treated with third-generation agents. We analyzed 100 patients who received such agents (paclitaxel, docetaxel, gemcitabine, irinotecan, or vinorelbine) for advanced NSCLC. The endpoint of the survey was the occurrence of severe neutropenia (grade 4). Risk factors significantly related to severe neutropenia were identified using logistic regression analysis. Of the 100 patients studied, the median age was 62.0 (32-81 years), and 77 (77.0%) were male. CEA 6.6 (0-2220) ng/dL and cytokeratin 19 fragment 21-1 (CYFRA) 4.8 (0.2-173.8) ng/dL before chemotherapy were higher than normal range. Severe neutropenia occurred in 36.0%, the incidence being highest in the first cycle (61.1%). In the univariate analysis, variables associated with severe neutropenia were sex, chest pain, absolute neutrophil count (ANC), Cr, CRP, and CYFRA. In the multivariate analysis, low CYFRA level was identified as a significant risk factor that contributed independently to chemotherapy-induced severe neutropenia (p<0.05). Our analysis suggests that low CYFRA level is the most important risk factor for severe neutropenia in advanced NSCLC patients after the first course of chemotherapy with third-generation agents.
Variation in protein binding ratio (PBR) of teicoplanin (TEIC) was investigated in continuous hemodiafiltration (CHDF) patients. TEIC is classified as a high PBR drug (≧90%), and it was reported that the PBR of TEIC decreased with an decrease in the serum albumin level in hypoalbuminemia patients. However, few reports can be found about the variation of PBR of TEIC for CHDF patient. An antibiotic activity is directly determined by the level of unbound antibiotics species (Cfree) in the target site, namely, an increase in the Cfree enhances the risks of TEIC as well as the therapeutic effect against Methicillin-resistant Staphylococcus aureus (MRSA). In this study, both the total concentration (Ctotal) and Cfree of TEIC were determined and the PBRs were compared between a patient with normal albumin level, hypoalbuminemia patients and CHDF patients. Similarly to the previous report, the lowering of PBR of TEIC was demonstrated in the hypoalbuminemia patients. On the other hand, the CHDF patients showed lower value of PBR suggesting some change in the protein binding ability, although showed higher values of serum albumin level in comparison with the hypoalbuminemia patients. It was not necessary to measure the Cfree value for the hypoalbuminemia patient routinely, but the monitoring of Cfree as well as Ctotal for the CHDF patients can be important for the proper TEIC use because of the potential specialty of PBR.
Heating a methylcellulose solution forms a thermal-reversible hydrogel. After the hydrogel forms, its properties change according to its temperature. However, the effects of heating this solution during storage and then cooling it are unclear. We investigated the effects of this heating and cooling on rheological and drug release characteristics. We prepared samples of methylcellulose solution (2% methylcellulose and 20% D-sorbitol) and examined them under two conditions: 1) storage for 24 hours at 4 to 30℃, 2) storage for 24 hours at 4 to 50℃, then cooling to 4℃ and maintained for 4 hours. We performed rheological investigations of viscosity, gelation temperature and gel strength, and examined the drug release characteristics by using a diffusion cell method with acetaminophen as the model drug. It was found that as the storage temperature rose, the methylcellulose solution increased in viscosity and the gelation temperature and gel strength changed. During storage at 30℃, the amount of drug released by the solution increased and the diffusion coefficient was high. When cooled to 4℃, the solution recovered its viscosity, gelation temperature, gel strength and drug release characteristics, regardless of the previous storage temperature. These results clarify that although the rheological and drug release characteristics of methylcellulose solution change with changes in storage temperature, the original characteristics are recovered after the solution is cooled to 4℃ and maintained at that temperature for four hours.
Although progesterone vaginal suppositories (hospital-formulated) are used for the treatment of infertility, their half-life is so short that multiple doses are required. In this study, we aimed to develop sustained-release vaginal suppositories suitable for clinical use which maintain an effective blood concentration by once-a-day treatment, and prepared 7 types of suppository containing the sustained-release progesterone tablets to characterize their sustained-release performance. We selected one candidate suppository among them, taking recovery rate, reproducibility, and hardness, as well as the sustained-release performance into consideration. The shell of the selected suppository is composed of VOSCO S-55 and progesterone for rapid release. The molded progesterone tablets for sustained release were embedded inside. The distribution of the weight and content of the suppository was limited, and the release rate of progesterone was significantly slower than that of a conventional progesterone suppository prepared in our hospital. The single-dose administration of the selected suppository to five healthy volunteers led to significant extension of the blood concentration. We also confirmed the rise of the basic value by multiple administration. The simulation comparison suggested that the blood progesterone concentration is controlled by once-a-day administration of the selected suppository better than twice-a-day administration of the conventional suppository. In conclusion, the sustained-release vaginal suppository prepared in this study was considered to be useful for clinical treatment.
This study sought to determine the effect of pharmacists wearing a mask on the consultation intention of patients who do not have a trusting relationship with the pharmacists. We conducted a questionnaire survey of customers at a Tokyo drugstore in August 2012. Subjects answered a questionnaire after watching two medical teaching videos, one in which the pharmacist was wearing a mask and the other in which the pharmacist was not wearing a mask. Data analysis was performed using a paired t-test and multiple logistic regression. The paired t-test revealed a significant difference in ‘Maintenance Problem’ between the two pharmacist situations. After excluding factors not associated with wearing a mask, multiple logistic regression analysis identified three independent variables with a significant effect on participants not wanting to consult with a pharmacist wearing a mask. Positive factors were ‘active-inactive’ and ‘frequency mask use’, a negative factor was ‘age’. Our study has shown that pharmacists wearing a mask may be a factor that prevents patients from consulting with pharmacist. Those patients whose intention to consult might be affected by the pharmacists wearing a mask tended to be younger, to have no habit of wearing masks preventively themselves, and to form a negative opinion of such pharmacists. Therefore, it was estimated that pharmacists who wear masks need to provide medical education by asking questions more positively than when they do not wear a mask in order to prevent the patient worrying about oneself.