サイエンス オ キバン トスル リンショウ ヤクザイ ギョウム ノ ジッセン

In the rapidly changing healthcare environment in recent years, appropriate and flexible response is required for health professionals including physicians, nurse and pharmacists. At Tokushima University Hospital, dedicated ward pharmacists have been allocated to every ward,providing instruction on the use of drugs, medication support, and counseling on medication, which has contributed to improved outcome of patients. In addition to their tasks such as drug dispensing,drug information management, and measurement and analyses of blood drug concentration,the pharmacists also positively collaborate as part of a nutrition support team, an infection control team, and other activities in the hospital. Rational pharmacy practice requires the ability to organize and apply evidence on a scientific basis to logically design drug therapy. In our department,we promote both clinical and basic research focused on the management of adverse effects and drug repositioning to achieve science-based pharmacy practice. Both pharmacy service and research require similar abilities research ability, such as capacity to think logically and problem resolution skill, is considered to be a basis for clinical competence. Pharmacists are expected to continuously deal flexibly with ever changing and expanding pharmacy services, and to contribute to team-based health care, by putting science-based clinical pharmacy services into practice

Drug-Repositioning Approaches Based on Database

Drug repositioning is a drug discovery strategy in which an existing drug is utilized as a therapeutic agent for a different disease. As information regarding the safety, pharmacokinetics, and formulation of existing drugs is already available, the cost and time required for drug development is reduced. Conventional drug repositioning has been dominated by a method involving the search for candidate drugs that act on the target molecules of an organism in a diseased state through basic research. However, recently, information hosted on medical information and life science databases have been used in translational research to bridge the gap between basic research in drug repositioning and clinical application. Here, we review an example of drug repositioning wherein candidate drugs were found and their mechanisms of action against a novel therapeutic target were identified via a basic research method that combines the findings retrieved from various medical and life science databases

ヤクリ サヨウ カラ ミタ ケンコウ ショクヒン

The several biologically active substances in foods were isolated as chemical compounds and each isolated chemical compound has been used as a drug in clinic. It is very difficult to make as harp distinction between drug and a chemical compound in functional food. At present, many functional food products with health claims are available in the local market. Since there is no distinct regulatory framework for functional foods, they are regulated as foods.However, some of these may have potentially disastrous side-effects and evaluation system of so-called health food is not established. We proposed that an isolated chemical compound in functional food, which has a pharmacological active effects, must handle as a drug and should be evaluated carefully in terms of its effectiveness and toxicity

Evaluation of potential complication of interstitial lung disease with abemaciclib and palbociclib treatments

Background: Various cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have demonstrated promising anti-tumor effects. The Japanese Ministry of Health, Labour and Welfare has issued a warning about interstitial lung diseases as an adverse effect of CDK4/6 inhibitors. However, a large-scale evaluation of potential complications has not been conducted to date, and the occurrence of these adverse effects is unclear. Aim: The aim of this study was to evaluate the clinical incidence of interstitial lung disease caused by two CDK4/6 inhibitors, abemaciclib and palbociclib, and assess the relationship between each drug and interstitial lung disease. Methods and results: We evaluated the relationship between the CDK4/6 inhibitors (abemaciclib and palbociclib) and interstitial lung disease in clinical practice using data from the Japanese Adverse Drug Event Report (JADER) database and FDA Adverse Event Reporting System (FAERS) to detect adverse event signals with reported odds ratios (RORs). Furthermore, we performed an adverse event-time analysis for each drug using data from the JADER database to examine the time of onset of the adverse events. The analysis of the reports in the JADER database showed that the lower limit of the 95% confidence interval (CI) of ROR for abemaciclib was >1 regardless of age, and a signal was detected. Interstitial lung disease associated with abemaciclib and palbociclib use has been reported, with an average onset period from treatment initiation [median (25th-75th quartile)] of 65.1 [56.0 days (25.3-98.3 days)] and 53.1 days [38.0 days (10.8-76.0 days)], respectively. The analysis of the reports in the FAERS showed that the lower limit of the 95% CI of the ROR for the two drugs was >1, and a signal was detected. Conclusion: Treatment with abemaciclib and palbociclib is associated with a potential complication of interstitial lung disease, regardless of age

Evaluation of Potential Complications of Interstitial Lung Disease Associated With Antiandrogens Using Data From Databases Reporting Spontaneous Adverse Effects

From 2002 to 2018, the number of patients with prostate cancer significantly increased from 679,023 to 1276,106 worldwide. Total prostatectomy (including robot-assisted prostatectomy), radiation therapy, and pharmacological treatment are commonly used to treat prostate cancer. The Chief of the Pharmaceutical Safety Division, that is, the Federation of Pharmaceutical Manufacturers’ Associations of Japan (FPMAJ), recently called for the revision of package inserts for ethical drugs. However, the pathogenesis of interstitial lung disease (ILD), a serious drug-induced adverse effect, remains unclear. Moreover, there have been no large-scale evaluations of potential complications associated with currently used antiandrogens, which are commonly employed to treat prostate cancer. Hence, ILD, as an adverse event, remains poorly understood. Therefore, we conducted a survey of reports in the Japanese Adverse Drug Event Report (JADER) database to investigate the potential association between the reporting of ILD and antiandrogen drug use in clinical practice. The occurrence of ILD was investigated by evaluating the relationship between antiandrogen drug use and ILD. Adverse event signals were detected with reporting odds ratios (RORs), using data from the JADER and FDA Adverse Event Reporting System (FAERS) databases, for the analysis of post-marketing adverse event reports. The JADER was used to examine the time profile of adverse event occurrence for each drug, whereas the FAERS was used to screen cases of unknown adverse events and analyze their trends of occurrence. The analysis of data from both databases revealed the 95% confidence interval lower limits of ROR for bicalutamide and flutamide to be > 1, and adverse event signals were detected following the use of either drug. While caution should be exercised for drugs that are new to the market, we conclude that drugs with similar therapeutic effects that have been in use for a long period should also be re-examined for potential adverse events

Pharmacological approach for drug repositioning against cardiorenal diseases

New applications of approved clinically used drugs are being discovered. Drug repositioning is a proposed strategy for developing these drugs as therapeutic agents for different diseases. Currently, approximately 2000 drugs are used in Japan. However, the compound targets and pathways involved in the pharmacological actions of 70-80% of these drugs have not been adequately clarified. Pharmacological examination of approved drugs is an important task in drug repositioning and vital for improving drug development efficiency. This review reports that angiotensin II type 1 receptor blockers show receptor-independent effects against reactive oxygen species generation in renal cells. Additionally, nitrosonifedipine has an antioxidative effect and protects endothelial cells against oxidative stress, and pioglitazone has multiple effects that improve dysfunctions in vascular control regulated by adrenergic and calcitonin gene-related peptide-containing nerves in animal models of diabetes. These data suggest that some approved drugs could be useful for treating cardiorenal diseases. Since cardiorenal diseases are likely to have chronic pathological conditions and require chronic drug administration, highly safe drugs are needed. Compared to newly developed drugs, drug repositioning of approved drugs with safety information is considered a particularly useful technique for searching new treatments for cardiorenal diseases

Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice

Purpose: Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear. Methods: C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into 3 groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups. Results: Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 (DMT1) and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 (BMP6) and CCAAT/enhancer binding protein alpha (C/EBPα), which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by administration of an ARB. Conclusions: ANG II altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution

Effect of Deferoxamine on Renal Fibrosis

Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases (CKD). Although several mechanisms underlying renal fibrosis and candidate drugs for its treatment have been identified, the effect of iron chelator on renal fibrosis remains unclear. In the present study, we examined the effect of an iron chelator, deferoxamine (DFO), on renal fibrosis in mice with surgically induced unilateral ureter obstruction (UUO). Mice were divided into 4 groups: UUO with vehicle, UUO with DFO, sham with vehicle, and sham with DFO. One week after surgery, augmented renal tubulointerstitial fibrosis and the expression of collagen I, III, and IV increased in mice with UUO; these changes were suppressed by DFO treatment. Similarly, UUO-induced macrophage infiltration of renal interstitial tubules was reduced in UUO mice treated with DFO. UUO-induced expression of inflammatory cytokines and extracellular matrix proteins was abrogated by DFO treatment. DFO inhibited the activation of the transforming growth factor-β1 (TGF-β1)-Smad3 pathway in UUO mice. UUO-induced NADPH oxidase activity and p22phox expression were attenuated by DFO. In the kidneys of UUO mice, divalent metal transporter 1, ferroportin, and ferritin expression was higher and transferrin receptor expression was lower than in sham-operated mice. Increased renal iron content was observed in UUO mice, which was reduced by DFO treatment. These results suggest that iron reduction by DFO prevents renal tubulointerstitial fibrosis by regulating TGF-β-Smad signaling, oxidative stress, and inflammatory responses

Rho-associated protein kinase and cyclophilin a are involved in inorganic phosphate-induced calcification signaling in vascular smooth muscle cells

Arterial calcification, a risk factor of cardiovascular events, develops with differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Cyclophilin A (CypA) is a peptidyl-prolyl isomerase involved in cardiovascular diseases such as atherosclerosis and aortic aneurysms, and rho-associated protein kinase (ROCK) is involved in the pathogenesis of vascular calcification. CypA is secreted in a ROCK activity-dependent manner and works as a mitogen via autocrine or paracrine mechanisms in VSMCs. We examined the involvement of the ROCK-CypA axis in VSMC calcification induced by inorganic phosphate (Pi), a potent cell mineralization initiator. We found that Pi stimulated ROCK activity, CypA secretion, extracellular signal-regulated protein kinase (ERK) 1/2 phosphorylation, and runt-related transcription factor 2 expression, resulting in calcium accumulation in rat aortic smooth muscle cells (RASMCs). The ROCK inhibitor Y-27632 significantly suppressed Pi-induced CypA secretion, ERK1/2 phosphorylation, and calcium accumulation. Recombinant CypA was found to be associated with increased calcium accumulation in RASMCs. Based on these results, we suggest that autocrine CypA is mediated by ROCK activity and is involved in Pi-induced ERK1/2 phosphorylation following calcification signaling in RASMCs