研究内容

臨床薬剤学分野では、研究室の最終目標を「患者様の心身ともに健全な生活の確保」とし、創造力豊かで、コミュニケーション能力を併せ持った人材の育成に主眼をおいて、日々研究に励んでいます。

研究内容は精神疾患(治療抵抗性うつ病)の病態機序の解明研究、意欲・動機付けの発現機構研究、抗がん剤投与による精神機能変化の解明研究、炎症時の精神機能変化の解明といった精神神経薬理研究ならびに医薬品による有害作用の発現機序解明研究、診療科と共同で免疫抑制剤、抗がん剤の血中濃度解析からの医薬品適正使用研究等を行っています。

1. 精神疾患発症の病態解明および次世代の医薬品創薬研究

  1. 治療抵抗性うつ病の病態解明および次世代の抗うつ薬創薬研究
  2. 脳内自己刺激行動を用いた意欲・動機付けの脳内発現機構研究
  3. 抗がん剤投与による精神機能変化に関する研究
  4. 炎症による精神機能変化に関する研究
  5. 神経変性疾患におけるグリア細胞機能変化に関する研究

2.医薬品による有害作用の発現機序解明と予防対策の確立

  1. 重合開始剤による有害事象の機序解明研究
  2. 分子標的治療薬の血中濃度解析と有害事象に関する研究

3. がんに対する分子標的薬の耐性とその克服研究

  1. がんに対する分子標的薬の耐性とその克服

4. 医薬品の適正使用研究

  1. 抗がん剤と既存医薬品との併用投与による抗がん作用増強効果に関する研究
  2. 医薬品関連インシデントに関する発生要因および予防対応策確立

5. Pharmaceutical care実践のための基盤研究

  1. 抗がん剤投与患者の精神機能変化に関する研究
  2. 術後せん妄の発症要因に関する研究

臨床薬学研究

薬剤師が「チーム医療」に加わることで患者さんの病態改善に貢献できる

薬剤師法第1条では薬剤師の任務が書かれています。「薬剤師は、調剤、医薬品の供給その他薬事衛生をつかさどることによって、公衆衛生の向上及び増進に寄与し、もって国民の健康な生活を確保するものとする」。つまり、薬剤師の任務は「調剤」、「医薬品の供給」「その他薬事衛生」となります。

現在、薬剤師の基本的任務には変わりがないものの、様々な関与および貢献が求められるようになってきました。その例として、「がん」「感染制御」「精神科」「妊婦・授乳婦」「HIV感染症」等の専門薬剤師制度が導入され、薬剤師の疾患に対する専門性も必要となってきました。平成22年4月には厚生労働省医政局長より、医療スタッフの「協働・連携によるチーム医療の推進について」が通知されました。その中で薬剤師は「近年、医療技術の進展とともに薬物療法が高度化しているため、医療の質の向上及び医療安全の確保の観点から、チーム医療において薬剤の専門家である薬剤師が主体的に薬物療法に参加することが非常に有益である。」と明記されています。具体的には、1.薬剤選択、投与量、投与方法、投与期間等について、医師に対して積極的な処方の提案、2.薬物療法を受けている患者(在宅の患者を含む。)に対し、薬学的管理(患者の副作用の状況の把握、服薬指導等)を行う、3.薬物の血中濃度や副作用のモニタリング等に基づき、副作用の発現状況や有効性の確認を行うとともに、医師に対し、必要に応じて薬剤変更等の提案、4.薬物療法の経過等を確認した上で、医師に対し、前回の処方内容と同一の内容の処方の提案等が明記されています。つまり、薬剤師はこれまでの「調剤」「医薬品の供給」「薬事衛生」のみならず、「その他薬事衛生」の「その他」の部分の充実が必要となっています。

そこで、薬剤師がチーム医療に積極的に参画することで、患者の病態改善に寄与できた私たちの研究を展開しています。

 

Our research interest lies in the pharmacological and clinical analysis of the central nervous system, and the elucidation of adverse events with the goal of understanding the theory establishment of Pharmaceutical care.

Current topics include,

  1. Development of animal models of treatment-resistant depression for hyperactivity in the HPA axis of rats or mice.
    Psychoendocrinology studies of depressed patients focus on the disregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Abnormalities in the HPA axis have been noted in depressed patients. Numerous data have demonstrated the existence of reciprocal interactions between the central serotonin (5-HT) system and HPA axis. These interactions are of particular relevance when considering pathological conditions, such as depression, in which modifications of both the 5-HT system and HPA axis have been evidenced. In our laboratory, we examined the effects of adrenocorticotropic hormone (ACTH) on the immobilization of rats in the forced swim test and on wet-dog shakes induced by DOI, a 5-HT2 receptor agonist with the administration of imipramine and lithium. The reduction of immobility, induced by the chronic administration of imipramine for 15 days, was blocked by treatment with ACTH for 14 days, a chronic ACTH treatment for 14 days increased the wet-dog shake response. This effect of ACTH was not inhibited by 14-day administration of imipramine. Accordingly, the chronic treatment of rats with ACTH may prove to be an effective model for antidepressant-treatment-resistant depression. We believe that behavioral pharmacological and molecular biological research into the interaction between 5-HT and the HPA axis will elucidate the pathogenesis of depression or antidepressant-treatment-resistant depression and the mechanism of antidepressant action.
  2. Mechanisms of neurogenesis in the hippocampus in relation to antidepressive effects.
    Chronic treatment with antidepressants may increase cell proliferation and cell survival and reverse stress-induced decreases in hippocampal cell proliferation and neurogenesis. The ability to promote hippocampal neurogenesis is a feature of both classical antidepressants, such as tricyclic drugs, and selective serotonin re-uptake inhibitors. Moreover, hippocampal cell proliferation and neurogenesis might be key factors in the actions of antidepressant drugs. We previously reported that the chronic administration of ACTH significantly decreased the number of 5-bromo-2’-deoxyuridine (BrdU) and Ki-67 (an endogenous marker of cell proliferation)-positive cells compared with the control value in the subgranular zone (SGZ) of the hippocampal dentate gyrus. This effect was not influenced by the chronic administration of imipramine or lithium, but was reversed by the coadministration of imipramine and lithium for 14 days in ACTH-treated rats. These results support the notion that imipramine and lithium would improve the efficacy of treatment for resistant depression by triggering cell proliferation.
  3. Cytotoxicity of the Polymerization Agent, 2-Methyl-4’-(methylthio)- 2- morpholinopropiophenone (MTMP) and 1-Hydroxycyclohexyl Phenyl Ketone (Irgacure 184) on Human Monocytes.
    Recently, there has been a transition from glass to polyethylene (PE) injection containers in Japan, because plastic ampoules are less breakable as well as being readily disposable. While PE containers are mainly composed of polyethylene, they also include antioxidants, slip agent, and anti-blocking agent. Because of the frequent, widespread use of plastic products, chemicals such as bisphenol A, nonylphenol and phthalate esters, which are used in the production of plastics as raw materials to be polymerized or as plasticizers, are a major concern. In previous studies, many research groups have analyzed the toxicity of endocrine-disrupting chemicals. Plasticizers have been shown to elute at a constant rate from plastic products into the environment, and certain members of this chemical class, such as di-(2-ethylhexyl)-phthalate (DEHP), have been shown to cause reproductive and developmental toxicity and are suspected of being endocrine disruptors. In our current study, 2-methyl-4’-(methylthio)-2-morpholinopropiophenone (MTMP) and 1-Hydroxycyclohexyl Phenyl Ketone (1-HCHPK) were detected in the injection solution from intravenous (i.v.) fluid bags. Additionally, we found that MTMP and 1-HCHPK were cytotoxic to human monocytes. Although mechanisms for the cytotoxicity of photoinitiators were not elucidated in this study, our data support the hypothesis that the cellular proliferation rate plays a role in the observed cellular toxicity. In future studies, we will clarify the possible health risks of photoinitiator accumulation in human cells.
  4. Pharmaceutical care of patients treated with antidepressants.
    The incidence of depressed patients is increasing worldwide, and depression has become the most common cause of suicide. Approximately 30,000 people have
    committed suicide each year from 1998 to the present, in Japan, this is a very important issue.Against this background, it is hoped that the clinical activities of pharmacists will enhance the quality of drug therapy. Antidepressant drugs, such as selective serotonin re-uptake inhibitors, serotonin noradrenaline re-uptake inhibitors, noradrenergic and specific serotonergic antidepressants, and tricyclic antidepressants have been used for many years. These drugs require long-term treatment. Depression causes mood impairment and influences the quality of life (QOL); thus, treatment with antidepressants is inseparably linked to the patient’s QOL, including the maintenance and improvement of drug compliance. We are now focusing on the pharmacists’ actions improve subjective QOL in depressed patients.