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系統識別號 U0026-0812200915191341
論文名稱(中文) 降血壓藥品對於老年人睡眠之影響
論文名稱(英文) The Impacts of Antihypertensive Drugs Causing Insomnia in the Elderly Hypertensive Patients
校院名稱 成功大學
系所名稱(中) 臨床藥學研究所
系所名稱(英) Institute of Clinical Pharmacy
學年度 97
學期 2
出版年 98
研究生(中文) 蘇俊中
研究生(英文) Jyun-jhong Su
電子信箱 s6696401@mail.ncku.edu.tw
學號 s6696401
學位類別 碩士
語文別 中文
論文頁數 148頁
口試委員 召集委員-林立人
指導教授-高雅慧
口試委員-林嘉音
口試委員-張志欽
中文關鍵字 安眠鎮靜劑  失眠  高血壓  乙型交感受體阻斷劑  老年族群 
英文關鍵字 insomnia  beta-blockers  hypertension  sedative hypnotics  older adults 
學科別分類
中文摘要 研究背景
約有43%的老年族群有難以入睡或維持睡眠困難的失眠情形發生,而失眠會造成憂鬱症或心血管疾病的問題產生。另外,因失眠的情況,被處方安眠鎮靜劑的情況相當普遍,而老年族群長期使用安眠鎮靜劑,已證實會提高跌倒、車禍或心智缺損的風險。然而,治療高血壓藥品之一的beta-blockers已證實與失眠的發生有其關聯性。但老年高血壓病患卻常使用beta-blockers治療其高血壓或其他併發症。因此,本研究目的為探討老年高血壓病患使用beta-blockers與造成失眠或處方安眠鎮靜劑之關聯性。

研究方法
利用2000~2004年全民健康保險資料庫,對象為2003年1月1日至2003年12月31日期間,年齡大於65歲(含),且第一次被登記高血壓相關診斷碼(401~405),且第一次被處方降血壓藥品之高血壓病患。以發生失眠或處方安眠鎮靜劑有無分成case候選組及control候選組,再以年齡、性別、追蹤時間及納入日期月份作1:6的配對,找到真正的case組及control組。利用條件式羅吉斯回歸法分析beta-blockers的使用與失眠或處方安眠鎮靜劑之關聯性。

研究結果
在配對年齡、性別、納入月份及追蹤時間後,case組共有5,325 人,control組共有31,950人,最終研究族群為37,275人。在影響睡眠因子方面,以慢性疼痛 (41.70%)為最多,以單一藥品治療高血壓 (67.27%)最多,並且以單一beta-blockers使用者 (97.07%)最多。正在使用beta-blockers (current use)顯著提高失眠或處方安眠鎮靜劑 (adjusted OR, 1.704 [95% CI, 1.576~1.842]),而propranolol (adjusted OR, 2.781 [95% CI, 2.335~3.310])、metoprolol (adjusted OR, 2.129 [95% CI, 1.310~3.460])、betaxolol (adjusted OR, 2.094 [95% CI, 1.262~3.472])、carteolol (adjusted OR, 2.997 [95% CI, 1.295~6.937])、acebutolol (adjusted OR, 1.808 [95% CI, 1.157~2.827])、atenolol (adjusted OR, 1.734 [95% CI, 1.540~1.953])、bisoprolol (adjusted OR, 1.468 [95% CI, 1.152~1.871])、carvedilol (adjusted OR, 1.643 [95% CI, 1.195~2.260])及labetalol (adjusted OR, 3.039 [95% CI, 2.152~4.292])也顯著提高其風險,而其他種類之beta-blockers則沒有增加其風險。若與atenolol 為基準,propranolol (adjusted OR, 1.711 [95% CI, 1.182~2.477])及metoprolol (adjusted OR, 2.291 [95% CI, 1.044~5.029])也顯著提高其風險。非選擇性beta-blockers 之使用 (adjusted OR, 1.591 [95% CI, 1.130~2.238])比具有β1-selective beta-blockers 顯著增加失眠或被處方安眠鎮靜劑之風險。另外,高親脂性beta-blockers 顯著增加其風險 (adjusted OR, 1.418 [95% CI, 1.034~1.944])。在累積劑量部份,使用高累積劑量的atenolol相較於低累積劑量沒有顯著提高安眠或被處方安眠鎮靜劑之風險。

研究結論
老年高血壓族群使用beta-blockers 30天內會顯著提高失眠或處方安眠鎮靜劑之風險。在不同種類之beta-blockers方面,propranolol、metoprolol、atenolol、betaxolol、carteolol、acebutolol、bisoprolol、carvedilol及labetalol會提高其風險,而其他種類之beta-blockers沒有顯著增加其風險。
英文摘要 Background
Approximately 43% of the elderly have the symptoms of insomnia such as difficulty in falling asleep or maintaining sleep. Insomnia may cause some adverse outcomes such as depression or cardiovascular disease according to previous studies. It has been proved that insomnia would increase the risk of fracture, vehicle accidents or cognitive impairment when the elderly took sedative hypnotics over a long period of time. Furthermore, beta blockers which are one type of antihypertensive drugs have been reported to cause insomnia. Furthermore, elderly hypertensive patients usually take beta-blockers for hypertension or other complications. Therefore, this study is aimed to investigate the association between beta-blockers and insomnia or sedative hypnotics prescribed in the elderly hypertensive patients.
Methods
We included hypertensive patients who were newly diagnosed with hypertension with ICD9-CM coded of ‘401-405’ in ambulatory department, the new prescription of antihypertensive drugs and older than 65 years-old in non-sampled National Health Insurance claims database from 1 Jan 2003 through 31 Dec 2003. Case candidates were defined as those who received the diagnosis of insomnia or sedative hypnotics prescribed and the other are control candidates. Cases were matched to control subjects for age (±3 years) at the cohort entry, gender, calendar month of admission date and duration of follow up. Moreover, we use conditional regression to analyze the association between beta-blockers and insomnia or sedative hypnotics prescribed in the elderly hypertensive patients.
Results
We identified 5,325 case patients and 31,950 control patients after matching factors. The common affecting sleep factors were chronic pain (41.70%). Mono-therapy (67.27%) is the most treatment for hypertension and mono-beta-blocker users (97.07%) is the major beta-blockers users. Current beta-blockers use was associated with an increasing risk of insomnia or being prescribed with sedative hypnotics (adjusted OR, 1.704 [95% CI, 1.576~1.842]). Uses of propranolol (adjusted OR, 2.781 [95% CI, 2.335~3.310]), metoprolol (adjusted OR, 2.129 [95% CI, 1.310~3.460]), betaxolol (adjusted OR, 2.094 [95% CI, 1.262~3.472]), carteolol (adjusted OR, 2.997 [95% CI, 1.295~6.937]), acebutolol (adjusted OR, 1.808 [95% CI, 1.157~2.827]), atenolol (adjusted OR, 1.734 [95% CI, 1.540~1.953]), bisoprolol (adjusted OR, 1.468 [95% CI, 1.152~1.871]), carvedilol (adjusted OR, 1.643 [95% CI, 1.195~2.260]) and labetalol (adjusted OR, 3.039 [95% CI, 2.152~4.292]) also increased the risk. Compared to atenolol, propranolol (adjusted OR, 1.711 [95% CI, 1.182~2.477]) and metoprolol (adjusted OR, 2.291 [95% CI, 1.044~5.029]) use increased the risk significantly. Compared to selective β1 blockers, non-selective beta-blockers use increased the risk (adjusted OR, 1.591 [95% CI, 1.130~2.238]). In addition, compared to low lipophilic beta-blockers use, higher lipophilic beta-blockers use increased the risk either (adjusted OR, 1.418 [95% CI, 1.034~1.944]).
Conclusion
Beta-blockers therapy in the elderly hypertensive patients started within the past 30 days was associated with an increased risk of insomnia or sedative hypnotics prescribed. In addition, propranolol、metoprolol, atenolol, betaxolol, carteolol, acebutolol, bisoprolol, carvedilol, and labetalol also increased the risk while other beta-blockers were not.
論文目次 中文摘要..................................................I
英文摘要................................................III
誌謝......................................................V
目錄.....................................................VI
表目錄....................................................X
圖目錄...................................................XI
第一篇 降血壓藥品對於老年人睡眠之影響....................1
第一章 研究背景..........................................1
第二章 文獻回顧..........................................3
第一節 失眠之通論........................................3
2.1.1 失眠之診斷標準......................................3
2.1.2 失眠之分類..........................................4
第二節 老年高血壓病患發生失眠之相關研究..................6
2.4.1 高血壓與失眠之關聯性................................6
2.4.2 老年高血壓患者之盛行率..............................7
2.4.3 降血壓藥品與失眠之關聯性............................7
2.4.4 Beta blockers之簡介.................................8
2.4.5 老年高血壓患者之降血壓藥品處方型態分析.............18
2.4.6 老年高血壓患者使用beta blockers影響生活品質之研究..18
第三節 老年人失眠之相關研究.............................19
2.2.1 睡眠生理之改變.....................................19
2.2.2 失眠盛行率.........................................21
2.2.3 失眠之不良預後影響.................................24
2.2.4 失眠之治療.........................................24
2.2.5 安眠藥品之處方型態.................................33
2.2.6 使用安眠藥品之相關風險.............................35
第四節 老年人造成失眠之因素.............................36
2.3.1 疾病因素...........................................36
2.3.2 藥品因素...........................................41
2.3.3 其他因素...........................................42
第三章 研究目的.........................................45
第四章 研究方法.........................................46
第一節 研究設計.........................................46
4.1.1 研究類型...........................................46
4.1.2 研究材料及工具.....................................46
4.1.3 納入對象...........................................47
4.1.4 排除標準...........................................47
第二節 研究變項及操作定義...............................49
4.2.1 研究對象分組及研究藥品定義.........................49
4.2.2 影響睡眠相關因子定義...............................50
4.2.3 Beta-blockers使用時間定義..........................51
4.2.4 不同種類beta-blockers分組定義......................52
4.2.5 不同影響睡眠機制 beta-blockers 之分組定義..........52
4.2.6 不同種類beta-blockers之累積劑量定義................52
第三節 資料處理流程.....................................53
4.3.1 檔案串聯...........................................53
4.3.2 研究流程...........................................54
第四節 統計方法.........................................55
4.4.1 統計工具...........................................55
4.4.2 統計模式設定.......................................55
4.4.3 資料分析方法.......................................55
第五章 研究結果.........................................58
第一節 病患基本特性分佈.................................58
第二節 老年高血壓患者發生失眠之安眠藥品處方型態分析.....64
5.2.1 老年失眠高血壓患者之基本特性分佈...................64
5.2.2 安眠鎮靜劑及非失眠適應症安眠藥品之分佈.............65
5.2.3 不適當安眠藥品之處方型態分佈.......................67
第三節 影響睡眠相關因子與失眠或被處方安眠鎮靜劑之關聯性.68
5.3.1 影響睡眠疾病與失眠或被處方安眠鎮靜劑之關聯性.......68
5.3.2 影響睡眠藥品與失眠或被處方安眠鎮靜劑之關聯性.......69
第四節 降血壓藥品與失眠或被處方安眠鎮靜劑之關聯性......69
5.4.1 合併降血壓藥品筆數與失眠或被處方安眠鎮靜劑之關聯性.69
5.4.2 使用beta-blockers與失眠或被處方安眠鎮靜劑之關聯性..69
5.4.3 不同種類beta-blockers與失眠或被處方安眠鎮靜劑之關聯
性.................................................70
5.4.4 不同影響睡眠機制的beta-blockers與失眠或被處方安眠鎮靜
劑之關聯性.........................................70
5.4.5 不同種類beta-blockers之累積劑量與安眠或被處方安眠鎮靜
劑之關聯性.........................................70
第六章 研究討論........................................77
第一節 研究族群人口特性................................77
第二節 安眠藥品處方型態評估............................78
6.2.1 老年失眠高血壓患者使用安眠藥品情形.................78
6.2.2 安眠鎮靜劑及非失眠適應症藥品之分佈情形.............78
6.2.3 不適當安眠藥品之處方型態分佈情形...................80
第三節 影響睡眠相關因子與失眠或被處方安眠鎮靜劑之關聯性探
討..............................................80
6.3.1 影響睡眠藥品與失眠或被處方安眠鎮靜劑之關聯性.......80
6.3.2 影響睡眠疾病與失眠或被處方安眠鎮靜劑之關聯性.......81
第四節 降血壓藥品與失眠或被處方安眠鎮靜劑之關聯性探討..82
6.4.1 合併降血壓藥品筆數與失眠或被處方安眠鎮靜劑之關聯性.82
6.4.2 使用beta-blockers與失眠或被處方安眠鎮靜劑之關聯性..83
6.4.3 不同種類beta-blockers與失眠或被處方安眠鎮靜劑之關聯
性.................................................84
6.4.4 不同影響睡眠機制的beta-blockers與失眠或被處方安眠鎮靜
劑之關聯性.........................................87
6.4.5 不同種類beta-blockers之累積劑量與安眠或被處方安眠鎮靜
劑之關聯性.........................................88
第五節 研究限制........................................95
第七章 結論與建議......................................96
第八章 未來研究方向....................................97
第二篇 臨床藥事服務-建構化學治療藥品交互作用資料庫.....98
第一章 目的............................................98
第二章 方法............................................99
第一節 建立化學治療藥品交互作用資料庫..................99
第二節 化學治療藥品交互作用之臨床建議.................100
第三章 結果...........................................103
第四章 未來展望與建議.................................134
附錄1 本研究相關疾病診斷碼 (ICD-9-CM)................145
附錄2 藥品ATC code...................................146
作者簡介................................................148
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