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研究生:張容維
研究生(外文):Jung-Wei Chang
論文名稱:Haloperidol和risperidone的血漿濃度與精神分裂症注意力之研究
論文名稱(外文):The Correlation between Attention Performance and Plasma Concentration of Schizophrenic Patients Treated with Haloperidol or Risperidone
指導教授:楊延光楊延光引用關係蘇聖芳蘇聖芳引用關係
指導教授(外文):Yen-Kang YangSheng-Fang Su
學位類別:碩士
校院名稱:國立成功大學
系所名稱:臨床藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:138
中文關鍵詞:注意力
外文關鍵詞:risperidonehaloperidolattentioncontinuous performance test
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研究背景 認知缺陷為精神分裂症疾病核心之一,且其嚴重度也和病人的預後有關。本研究以持續性注意力為指標。比較典型抗精神病藥haloperidol,及其結構類似的非典型抗精神病藥物risperidone在使用長達一年以上者,兩個精神分裂症之病人的持續性注意力是否有差異,及兩種藥物的血漿濃度與持續性注意力的關係。
研究方法 收入使用haloperidol或risperidone一年以上,在穩定門診的病患。第一部份用continuous performance test (CPT)測量兩組的持續性注意力。第二部分,以高能液相層析法分析兩種藥物的血中濃度與CPT得分的相關性。
結果 第一部份中haloperidol與risperidone兩組持續性注意力,無統計差異。第二部分中,haloperidol組並未發現血漿濃度與CPT測量值間有顯著相關,但在risperidone,發現遮蔽部分CPT的測量結果與risperidone血漿濃度呈現負相關(P<0.05),與9-hydroxyrisperidone/risperidone比值呈現正相關。
結論 由於haloperidol組和risperidone組的持續性注意力並沒有差異,且CPT所測得的持續性注意力和risperidone血漿濃度呈現負相關,與9-hydroxyrisperidone/risperidone呈現正相關。始能推論可能有二,一為:risperidone血漿濃度的升高,可能會使持續性注意力降低。對於少數CYP 2D6表型為poor metabolizer (PM)的患者,體內risperidone較易累積,可能會因血漿中risperidone的高濃度而影響其注意力,建議此少數患者使用時更需小心。二為:由於risperidone對CPT的療效尚未完全確定,若risperidone對CPT不影響的情況下,則可能影響9-hydroxyrisperidone/risperidone比例的基因,可能與控制持續性注意力有關。
Background In this study, cognitive deficits were compared between schizophrenics treated with haloperidol and risperidone. The association of cognitive deficits and blood concentration was also investigated.
Objective This naturalistic trial aimed to investigate the association between plasma concentration of haloperidol and risperidone on the cognitive function of patients with schizophrenia.
Methods The subjects were diagnosed schizophrenia according to the DSM-IV. The study consisted of two separate parts. Firstly, by conducting continuous performance test(CPT), the sustained attention of the two groups was observed. The second part was to analyze the relationships between plasma concentration of risperidone or haloperidol and the CPT results.
Results First part: There were no significant differences between the sustained attention results of both groups. Second part:There was no significant correlation between sustained attention and plasma concentration of haloperidol, either. However, negative correlation between the degraded part of CPT survey results and plasma concentration of risperidone was significant (g= -0.81, p=0.005), and positive correlation between the degraded part of CPT survey results and 9-hydroxyrisperidone/ risperidone was significant as well (g=-0.78, p=0.008).
Conclusion Based on the findings of this study, we can conclude these results in two ways. Firstly, since CYP 2D6 is less effective in converting risperidone into 9-hydroxyrisperidone, it may be valuable for poor metabolizers influenced by the higher dose of risperidone. Secondly, if risperidone didn’t influence the performance of CPT, then the genes controlling the ratio of 9-OH risperidone/risperidone may greatly influence sustained attention, too.
目 錄
中文摘要………………………………………………………………I
英文摘要………………………………………………………………II
誌謝……………………………………………………………………III
目錄……………………………………………………………………IV
縮寫表…………………………………………………………………VII
表目錄…………………………………………………………………VIII
圖目錄…………………………………………………………………X

第一章 緒論…………………………………………………………1
  第一節 研究背景………………………………………………1
  第二節 研究目的………………………………………………3
第二章 文獻回顧……………………………………………………4
  第一節 精神分裂症(Schizophrenia)……………………………4
    一、精神分裂症(Schizophrenia)……………………………4
    二、疾病症狀………………………………………………5
    三、診斷及預後……………………………………………7
    四、由神經化學系統來看精神分裂症……………………9
    五、精神分裂症的治療……………………………………12
  第二節 認知功能………………………………………………16
    一、認知功能(cognitive function)與精神分裂症…………16
    二、認知分述………………………………………………18
  第三節 抗精神分裂症藥物與認知功能的關係………………23
    一、抗精神分裂症藥物和認知功能的關係………………23
    二、Haloperidol, risperidone和注意力間的研究…………34
    三、研究中的共服藥物影響………………………………35
  第四節 Haloperidol及risperidone簡介…………………………36
    一、Haloperidol ……………………………………………36
      1.化學結構與安定性…………………………………36
      2.藥物動力學方面……………………………………37
      3.臨床適應症…………………………………………41
      4.一般使用原則………………………………………41
      5.不良反應及處理……………………………………42
    二、Risperidone ……………………………………………44
      1.化學結構與安定性…………………………………44
      2.藥物動力學…………………………………………44
      3.臨床適應症…………………………………………51
      4.對有危險性病人的建議……………………………53
      5.使用前安全注意事項………………………………54
      6.在懷孕以及哺乳婦女身上的使用…………………54
      7.對駕駛能力以及機械操作能力的影響……………55
      8.藥物使用過量………………………………………55
  第五節 血漿濃度與藥物副作用之間的關係…………………56
    一、分析方法和抽血時間點………………………………56
    二、藥物血漿濃度應用分述………………………………57
      1.Haloperidol …………………………………………57
      2.Risperidone …………………………………………61
第三章 研究方法……………………………………………………64
  第一節 研究設計………………………………………………64
    一、研究地點………………………………………………64
    二、病人選擇………………………………………………64
    三、研究用藥………………………………………………65
    四、研究流程………………………………………………65
  第二節 評估方式………………………………………………67
    一、評估工具簡介…………………………………………67
    二、血漿濃度測量方法……………………………………69
第四章 研究結果……………………………………………………72
  一、第一部分:Haloperidol及risperidone的比較………………72
  二、第二部分:藥物血漿濃度的測定…………………………75
第五章 討論…………………………………………………………98
第六章 結論與建議…………………………………………………106
參考文獻………………………………………………………………108
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