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佐匹克隆

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維基百科,自由的百科全書
佐匹克隆
臨床資料
商品名英語Drug nomenclatureImovane, Zimovane
AHFS/Drugs.com國際藥品名稱
懷孕分級
  • : C
依賴性極高
成癮性極高
給藥途徑口服片劑, 3.75mg (UK), 5 or 7.5 mg
ATC碼
法律規範狀態
法律規範
藥物動力學數據
生物利用度52-59%
藥物代謝Various 細胞色素 P450 肝酶
生物半衰期~5 -9 小時
排泄途徑尿液
識別資訊
  • (RS)-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate
CAS號43200-80-2  checkY
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard英語CompTox Chemicals Dashboard (EPA)
ECHA InfoCard100.051.018 編輯維基數據鏈接
化學資訊
化學式C17H17ClN6O3
摩爾質量388.81 g·mol−1
3D模型(JSmol英語JSmol
  • O=C(OC3c1nccnc1C(=O)N3c2ncc(Cl)cc2)N4CCN(C)CC4
  • InChI=1S/C17H17ClN6O3/c1-22-6-8-23(9-7-22)17(26)27-16-14-13(19-4-5-20-14)15(25)24(16)12-3-2-11(18)10-21-12/h2-5,10,16H,6-9H2,1H3 checkY
  • Key:GBBSUAFBMRNDJC-UHFFFAOYSA-N checkY

佐匹克隆(英語:Zopiclone),又譯唑吡酮,商品名宜眠安(英語:Imovane),香港濫用者俗稱其白瓜子、台灣稱樂比克[1][2];是一種用於治療失眠的藥物。

佐匹克隆雖然在BZ1受體上產生作用,它卻不屬於苯二氮類藥物,而是一種環吡咯酮衍生物。

不良反應

副作用最多見於臨床試驗中的味覺改變或味覺障礙(比如口中含有苦味或金屬味)通常這種味覺改變是短暫的,能持續至該藥物的半衰期過期。

佐匹克隆會引起類似於服用三唑侖之後造成的失憶症類型的記憶損傷[3]和服用氟硝西泮之後導致的駕駛技術降低,從而增加道路交通事故的風險,恐怕是最嚴重的副作用。所以這類副作用並不是只服用佐匹克隆之後出現的。[4][5]一項研究評估服用佐匹克隆對第二天駕駛技術的影響,之後發現駕駛技術的降低對社會的危害如同酒後駕車。但某些安眠藥例如扎來普隆,對第二天的駕駛技術沒有任何不利的影響。[6]夜間長期服用其他非苯二氮䓬類藥物也會出現白天停藥引發的焦慮[7]

比較常見的

不太常見的

耐藥性,依賴性和戒斷反應

佐匹克隆最初被宣稱是比傳統的苯二氮䓬類藥物更不容易產生依賴與戒斷反應的藥物,然而佐匹克隆可能比傳統的苯二氮䓬類藥物有更大的潛在依賴性,並已經被形容為「苯二氮䓬類藥物的變相」。[22][23][24]佐匹克隆應儘量避免在多數情況下長期使用,如果突然停藥尤其是長時間服用高劑量之後停藥,最嚴重的時候會導致患者癲癇譫妄精神錯亂)。[25][26]

在出版物《英國醫學雜誌》中沒有給出任何可以證明「佐匹克隆依賴性很小」的證據。事實上生理依賴康樂濫用和成癮後的戒斷症狀相似,這類症狀在苯二氮平類藥物停藥的時候經常遇到。戒斷症狀包括焦慮、心跳加速、震顫盜汗臉紅心悸,也會出現失眠加重的情況。[27]2007年美國曾經報道過有人在佐匹克隆戒斷排毒期間發生抽搐反應,但該人是長期服用高劑量佐匹克隆的濫用藥物者。[28]

如果連續服用佐匹克隆不到14天或者只是偶爾服用佐匹克隆,那麼產生依賴性的風險比較低。[29]然而這在一項僅服用7晚低劑量佐匹克隆的研究里是受爭議的。這項研究發現佐匹克隆停藥會引起顯著反跳性失眠。此外,苯二氮䓬類藥物之一的咪達唑侖服用7夜停藥之後無反跳性失眠,這表明佐匹克隆比苯二氮䓬類藥物有更明顯的耐藥性和依賴性的問題。[30]長期服用佐匹克隆而導致依賴的患者突然停藥會發生嚴重的戒斷症狀如精神錯亂,所以不應該突然停藥。[31]如果佐匹克隆已經服用超過數周,之後的服用藥量應該逐漸降低。或者直接改用等效劑量地西泮(俗稱「安定」),因為地西泮具有更長的半衰期,所以會使停藥更容易。然後過幾個月再逐漸減少其用量,以避免極嚴重又極易導致患者煩惱的停藥症狀(例如內坐立不安精神運動性激越腹痛高血壓幻覺癲癇焦慮症抑鬱症精神病等)。需要注意的是如果停藥做得太急劇的話,停藥症狀可能持續長達兩年。[32][33][34]

連續4星期晚上服用佐匹克隆之後,部分患者在白天停藥的時候出現了相關的焦慮症狀。然而白天停藥引發的焦慮在三唑侖藥物中並沒有那麼激烈,反而症狀時間更短暫。這令那些由於白天停藥而引發焦慮的患者更為憤怒。[35]

根據世界衛生組織英語:World Health Organisation)的說法,雖然佐匹克隆的分子不是苯二氮卓,但是其與苯二氮卓類藥物非常相似。世界衛生組織還指出,佐匹克隆與苯二氮卓類藥物具有交叉耐受性,服用期間也可替換為其他的苯二氮卓類藥物世界衛生組織在對佐匹克隆的審閱中發現戒斷症狀通常發生在這兩種藥物的其中一種服用劑量過大或者長時間服用佐匹克隆。其報道的戒斷症狀包括焦慮心動過速震顫盜汗失眠反彈、抽搐心悸臉紅[36]

特別注意事項

服用佐匹克隆的時候應當避免飲用酒精以及含有酒精的食物、飲料,例如當酒精和佐匹克隆一起服用時會互相增強效果,同時也會增加對藥物的依賴。[37]

肝病患者對佐匹克隆的戒除要比普通患者緩慢,除了一些對藥物的藥理作用有豐富經驗的患者。[38]

佐匹克隆服用之後也會使患者走路晃晃悠悠,老年患者服用之後也會增加摔倒的概率。多數老年人若不慎摔倒也會導致死亡,所以老年人服用之後應避免長時間的站立與走動。[39][40][41]

一些患有重症肌無力或者由於嚴重的慢性支氣管炎肺氣腫等肺部疾病導致呼吸儲備較差的患者,或者患有睡眠呼吸暫停症的患者不宜服用佐匹克隆,患有甲狀腺異常且沒有經過任何治療的患者也不宜服用。[42]

藥物濫用

在美國,佐匹克隆是著名的吸毒者濫用藥物之一,而且他們通常是從醫院獲取藥物。(美國某戒毒所發現5.1%的吸毒者在其治療中心報告了他們的佐匹克隆上癮)[來源請求]

濫用者經常與酒精飲料一起服用以達到安眠藥與酒精相結合的興奮感。患者濫用藥物的行為同樣存在會產生藥物依賴的風險,即使以後將服用量減小,但由於持續服藥時間過長,戒斷症狀在短時間內也不會消失。所以一些醫藥公司與相關人員建議處方藥量不得高於7至10天的服用量,原因就是擔心物質依賴藥物耐受身體依賴[43]

濫用佐匹克隆與酒精兩類藥物會導致服藥後的興奮,導致患者直接將該藥物當作娛樂性藥物進行濫用,同時也會長期違背醫囑用量去服用藥物。[44][45]一些曾有過濫用藥物或者曾經患有精神疾病的患者服用高劑量佐匹克隆可能會增加濫用藥物的風險。[46]

在生物體液中的檢測

佐匹克隆在人體中的含量可用色譜法血液血漿尿液當中進行測定。在正常的用量中,藥物在人體血漿中的含量通常低於100 μg/L(微克/升),但是在血漿當中藥物的含量超出100 μg/L尤其是發生在汽車駕駛員身上的時候,會影響他們的駕駛能力。一些服藥之後導致急性中毒的患者的含量通常在1000 μg/L以上。有屍檢報告指出一些由於急性藥物中毒的死者的血液含藥濃度通常在0.4-3.9 mg/L(毫克/升)。[47][48][49]

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外部連結