本页使用了标题或全文手工转换

佐匹克隆

维基百科,自由的百科全书
跳到导航 跳到搜索
佐匹克隆
Zopiclone.svg
Zopiclone ball-and-stick.png
系统(IUPAC)命名名称
(RS)-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate
临床数据
商品名 Imovane, Zimovane
Drugs.com 国际药品名称
妊娠分级
  • AU: C
  • US: C (不排除有风险的可能)
依赖性 极高
成瘾性 极高
给药途径 口服片剂, 3.75mg (UK), 5 or 7.5 mg
合法狀態
合法状态
药代动力学数据
生物利用度 52-59%
代谢 Various 细胞色素 P450 肝酶
生物半衰期 ~5 -9 小时
排泄 尿液
识别信息
CAS注册号43200-80-2 ✓
ATC代码 N05CF01
PubChem CID 5735
IUPHAR/BPS英语IUPHAR/BPS 7430
DrugBank DB01198 ✓
ChemSpider 5533 ✓
UNII 03A5ORL08Q ✓
KEGG D01372 ✓
ChEBI CHEBI:32315 ✓
ChEMBL英语ChEMBL CHEMBL135400 ✓
化学信息
化学式 C17H17ClN6O3
摩尔质量 388.808 g/mol

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。是一种短期治疗失眠的药物,但是非常容易导致成瘾。[1][2]

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。

不良反应[编辑]

副作用最多见于临床试验中的味觉改变或味觉障碍(比如口中含有苦味或金属味)通常这种味觉改变是短暂的,能持续至该药物的半衰期过期。

佐匹克隆会引起类似于服用三唑仑之后造成的失忆症类型的记忆损伤[3]和服用氟硝安定之后导致的驾驶技术降低,从而增加道路交通事故的风险,恐怕是最严重的副作用。所以这类副作用并不是只服用佐匹克隆之后出现的。[4][5]一项研究评估服用佐匹克隆对第二天驾驶技术的影响,之后发现驾驶技术的降低对社会的危害如同酒后驾车。但某些安眠药例如扎来普隆,对第二天的驾驶技术没有任何不利的影响。[6]夜间长期服用其他非苯二氮䓬类药物也会出现白天停药引发的焦虑[7]

比较常见的[编辑]

不太常见的[编辑]

耐药性,依赖性和戒断反应[编辑]

佐匹克隆最初被宣称是比传统的苯二氮䓬類藥物更不容易产生依赖与戒断反应的药物,然而佐匹克隆可能比传统的苯二氮䓬類藥物有更大的潜在依赖性,并已经被形容为“苯二氮䓬類藥物的变相”。[22][23][24]佐匹克隆应尽量避免在多数情况下长期使用,如果突然停药尤其是长时间服用高剂量之后停药,最严重的时候会导致患者癫痫谵妄精神错乱)。[25][26]

在出版物《英国医学杂志》中没有给出任何可以证明“佐匹克隆依赖性很小”的证据。事实上生理依赖康乐滥用和成瘾后的戒断症状相似,这类症状在苯二氮平类药物停药的时候经常遇到。戒断症状包括焦虑、心跳加速、震颤盗汗脸红心悸,也会出现失眠加重的情况。[27]2007年美国曾经报道过有人在佐匹克隆戒断排毒期间发生抽搐反应,但该人是长期服用高剂量佐匹克隆的滥用药物者。[28]

如果连续服用佐匹克隆不到14天或者只是偶尔服用佐匹克隆,那么产生依赖性的风险比较低。[29]然而这在一项仅服用7晚低剂量佐匹克隆的研究里是受争议的。这项研究发现佐匹克隆停药会引起显著反跳性失眠。此外,苯二氮䓬類藥物之一的咪达唑仑服用7夜停药之后无反跳性失眠,这表明佐匹克隆比苯二氮䓬類藥物有更明显的耐药性和依赖性的问题。[30]长期服用佐匹克隆而导致依赖的患者突然停药会发生严重的戒断症状如精神错乱,所以不应该突然停药。[31]如果佐匹克隆已经服用超过数周,之后的服用药量应该逐渐降低。或者直接改用等效剂量地西泮(俗称「安定」),因为地西泮具有更长的半衰期,所以会使停药更容易。然后过几个月再逐渐减少其用量,以避免极严重又极易导致患者烦恼的停药症状(例如内坐立不安精神运动性激越腹痛高血压幻觉癫痫焦虑症抑郁症精神病等)。需要注意的是如果停药做得太急剧的话,停药症状可能持续长达两年。[32][33][34]

连续4星期晚上服用佐匹克隆之后,部分患者在白天停药的时候出现了相关的焦虑症状。然而白天停药引发的焦虑在三唑仑药物中并没有那么激烈,反而症状时间更短暂。这令那些由于白天停药而引发焦虑的患者更为愤怒。[35]

根据世界卫生组织英语:World Health Organisation)的说法,虽然佐匹克隆的分子不是苯二氮卓,但是其与苯二氮卓类药物非常相似。世界卫生组织还指出,佐匹克隆与苯二氮卓类药物具有交叉耐受性,服用期间也可替换为其他的苯二氮卓类药物世界卫生组织在对佐匹克隆的审阅中发现戒断症状通常发生在这两种药物的其中一种服用剂量过大或者长时间服用佐匹克隆。其报道的戒断症状包括焦虑心动过速震颤盗汗失眠反弹、抽搐心悸脸红[36]

特别注意事项[编辑]

服用佐匹克隆的时候应当避免饮用酒精以及含有酒精的食物、饮料,例如当酒精和佐匹克隆一起服用时会互相增强效果,同时也会增加对药物的依赖。[37]

肝病患者对佐匹克隆的戒除要比普通患者缓慢,除了一些对药物的药理作用有丰富经验的患者。[38]

佐匹克隆服用之后也会使患者走路晃晃悠悠,老年患者服用之后也会增加摔倒的概率。多数老年人若不慎摔倒也会导致死亡,所以老年人服用之后应避免长时间的站立与走动。[39][40][41]

一些患有重症肌无力或者由于严重的慢性支气管炎肺气肿等肺部疾病导致呼吸储备较差的患者,或者患有睡眠呼吸暂停症的患者不宜服用佐匹克隆,患有甲状腺异常且没有经过任何治疗的患者也不宜服用。[42]

药物滥用[编辑]

在美国,佐匹克隆是著名的吸毒者滥用药物之一,而且他们通常是从医院获取药物。(美国某戒毒所发现5.1%的吸毒者在其治疗中心报告了他们的佐匹克隆上瘾)[來源請求]

滥用者经常与酒精饮料一起服用以达到安眠药与酒精相结合的兴奋感。患者滥用药物的行为同样存在会产生药物依赖的风险,即使以后将服用量减小,但由于持续服药时间过长,戒断症状在短时间内也不会消失。所以一些医药公司与相关人员建议处方药量不得高于7至10天的服用量,原因就是担心物质依赖药物耐受身体依赖[43]

滥用佐匹克隆与酒精两类药物会导致服药后的兴奋,导致患者直接将该药物当作娱乐性药物进行滥用,同时也会长期违背医嘱用量去服用药物。[44][45]一些曾有过滥用药物或者曾经患有精神疾病的患者服用高剂量佐匹克隆可能会增加滥用药物的风险。[46]

过量服用[编辑]

在生物体液中的检测[编辑]

佐匹克隆在人体中的含量可用色谱法血液血浆尿液当中进行测定。在正常的用量中,药物在人体血浆中的含量通常低于100 μg/L(微克/升),但是在血浆当中药物的含量超出100 μg/L尤其是发生在汽车驾驶员身上的时候,会影响他们的驾驶能力。一些服药之后导致急性中毒的患者的含量通常在1000 μg/L以上。有尸检报告指出一些由于急性药物中毒的死者的血液含药浓度通常在0.4-3.9 mg/L(毫克/升)。[47][48][49]

參考資料[编辑]

  1. ^ What's wrong with prescribing hypnotics?. Drug Ther Bull. December 2004, 42 (12): 89–93. PMID 15587763. doi:10.1136/dtb.2004.421289. 
  2. ^ Touitou Y. [Sleep disorders and hypnotic agents: medical, social and economical impact]. Ann Pharm Fr. July 2007, 65 (4): 230–8. PMID 17652991 (法语). 
  3. ^ Gorenstein C, Tavares SM, Gentil V, Peres C, Moreno RA, Dreyfus JF. Psychophysiological effects and dose equivalence of zopiclone and triazolam administered to healthy volunteers. Methodological considerations. Braz. J. Med. Biol. Res. 1990, 23 (10): 941–51. PMID 2101059. 
  4. ^ Gustavsen I, Bramness JG, Skurtveit S, Engeland A, Neutel I, Mørland J. Road traffic accident risk related to prescriptions of the hypnotics zopiclone, zolpidem, flunitrazepam and nitrazepam. Sleep Med. December 2008, 9 (8): 818–22. PMID 18226959. doi:10.1016/j.sleep.2007.11.011. 
  5. ^ Verster JC, Veldhuijzen DS, Patat A, Olivier B, Volkerts ER. Hypnotics and driving safety: meta-analyses of randomized controlled trials applying the on-the-road driving test. Curr Drug Saf. January 2006, 1 (1): 63–71. PMID 18690916. doi:10.2174/157488606775252674. 
  6. ^ Vermeeren A, Riedel WJ, van Boxtel MP, Darwish M, Paty I, Patat A. Differential residual effects of zaleplon and zopiclone on actual driving: a comparison with a low dose of alcohol. Sleep. March 2002, 25 (2): 224–31. PMID 11905433. 
  7. ^ Fontaine, R; Beaudry, P; Le, Morvan, P; Beauclair, L; Chouinard, G. Zopiclone and triazolam in insomnia associated with generalized anxiety disorder: a placebo-controlled evaluation of efficacy and daytime anxiety. International clinical psychopharmacology (PDF). Jul 1990, 5 (3): 173–183. ISSN 0268-1315. PMID 2230061. doi:10.1097/00004850-199007000-00002. 
  8. ^ Giercksky, Ke; Wickstrom, E. A dose-response study in situational insomnia with zopiclone, a new tranquilizer. Clinical therapeutics. 1980, 3 (1): 21–7. ISSN 0149-2918. PMID 6996815. 
  9. ^ Ratrema M, Guy C, Nelva A; 等. [Drug-induced taste disorders: analysis of the French Pharmacovigilance Database and literature review]. Therapie. 2001, 56 (1): 41–50. PMID 11322016 (法语). 
  10. ^ Nicholson, An; Stone, Bm. Zopiclone: sleep and performance studies in healthy man.. International pharmacopsychiatry. 1982,. 17 Suppl 2: 92–7. ISSN 0020-8272. PMID 7188378. 
  11. ^ Subhan, Z; Hindmarch, I. Effects of zopiclone and benzodiazepine hypnotics on search in short-term memory.. Neuropsychobiology. 1984, 12 (4): 244–8. ISSN 0302-282X. PMID 6152563. doi:10.1159/000118146. 
  12. ^ Channer, Ks; Dent, M; Roberts, Cj. The effect of posture at the time of administration on the central depressant effects of the new hypnotic zopiclone.. British Journal of Clinical Pharmacology. Dec 1984, 18 (6): 879–86. ISSN 0306-5251. PMC 1463687. PMID 6529528. doi:10.1111/j.1365-2125.1984.tb02559.x. 
  13. ^ Monchesky, Tc; Billings, Bj; Phillips, R. Zopiclone: a new nonbenzodiazepine hypnotic used in general practice.. Clinical therapeutics. 1986, 8 (3): 283–91. ISSN 0149-2918. PMID 3521857. 
  14. ^ Bocca ML, Denise P. Residual effects of hypnotics on disengagement of spatial attention. J. Psychopharmacol. (Oxford). 2000, 14 (4): 401–5. PMID 11198059. doi:10.1177/026988110001400409. 
  15. ^ Moloney I, Breen EG, El Hassan H, Kelly BD. Extreme agitation occurring with zopiclone. Ir Med J. June 2007, 100 (6): 511. PMID 17668690. 
  16. ^ Ferentinos P, Paparrigopoulos T. Zopiclone and sleepwalking. Int. J. Neuropsychopharmacol. February 2009, 12 (1): 141–2. PMID 18925983. doi:10.1017/S1461145708009541. 
  17. ^ Warot, D; Bensimon, G; Danjou, P; Puech, Aj. Comparative effects of zopiclone, triazolam and placebo on memory and psychomotor performance in healthy volunteers.. Fundamental & clinical pharmacology. 1987, 1 (2): 145–52. ISSN 0767-3981. PMID 3679064. doi:10.1111/j.1472-8206.1987.tb00553.x. 
  18. ^ Fava GA. Amnestic syndrome induced by zoplclone. Eur. J. Clin. Pharmacol. 1996, 50 (6): 509. PMID 8858280. doi:10.1007/s002280050149. 
  19. ^ Silva A, Collao A, Orellana M, Meléndez J, Caviedes P, Cárdenas AM. Zopiclone, but not brotizolam, impairs memory storage during sleep. Neurosci. Res. October 2003, 47 (2): 241–3. PMID 14512149. doi:10.1016/S0168-0102(03)00170-6. 
  20. ^ David M, Breton JL, Guy I, Vandel S. [Zopiclone and delirium: a case report]. Therapie. 1998, 53 (1): 78–80. PMID 9773104 (法语). 
  21. ^ Hussain N, MacKinnon M, Akbari A. Zopiclone-induced acute interstitial nephritis. Am. J. Kidney Dis. May 2003, 41 (5): E17. PMID 12778435. doi:10.1016/S0272-6386(03)00382-2. 
  22. ^ Bramness JG; Olsen H. [Adverse effects of zopiclone]. Tidsskrift for den Norske laegeforening. 1998, 118 (13): 2029–32. PMID 9656789. 
  23. ^ Luty S, Sellman D. Imovane—a benzodiazepine in disguise. N. Z. Med. J. July 1993, 106 (959): 293. PMID 8321452. 
  24. ^ Deveaux M, Chèze M, Pépin G. The role of liquid chromatography-tandem mass spectrometry (LC-MS/MS) to test blood and urine samples for the toxicological investigation of drug-facilitated crimes. Ther Drug Monit. April 2008, 30 (2): 225–8. PMID 18367985. doi:10.1097/FTD.0b013e3181676186. 
  25. ^ Hypnotic dependence: zolpidem and zopiclone too. Prescrire Int. February 2001, 10 (51): 15. PMID 11503851. 
  26. ^ Wong CP, Chiu PK, Chu LW. Zopiclone withdrawal: an unusual cause of delirium in the elderly (PDF). Age Ageing. September 2005, 34 (5): 526–7. PMID 16107464. doi:10.1093/ageing/afi132. 
  27. ^ Jones IR, Sullivan G. Physical dependence on zopiclone: case reports. BMJ. January 1998, 316 (7125): 117. PMC 2665371. PMID 9462317. doi:10.1136/bmj.316.7125.117. 
  28. ^ Aranko, K; Henriksson, M; Hublin, C; Seppäläinen, Am. Misuse of zopiclone and convulsions during withdrawal.. Pharmacopsychiatry. Jul 1991, 24 (4): 138–40. ISSN 0176-3679. PMID 1754610. doi:10.1055/s-2007-1014457. 
  29. ^ Anderson, Aa. Zopiclone and nitrazepam: a multicenter placebo controlled comparative study of efficacy and tolerance in insomniac patients in general practice.. Sleep. 1987,. 10 Suppl 1: 54–62. ISSN 0161-8105. PMID 3326116. 
  30. ^ Mendelson WB, Jain B. An assessment of short-acting hypnotics. Drug Saf. October 1995, 13 (4): 257–70. PMID 8573298. doi:10.2165/00002018-199513040-00005. 
  31. ^ Harter C, Piffl-Boniolo E, Rave-Schwank M. [Development of drug withdrawal delirium after dependence on zolpidem and zoplicone]. Psychiatr Prax. November 1999, 26 (6): 309. PMID 10627964 (德语). 
  32. ^ sanofi-aventis Canada Inc. IMOVANE (zopiclone) Tablets, 5.0 mg and 7.5 mg (PDF). October 30, 2008 [2014-08-27]. (原始内容 (PDF)存档于2016-03-14). 
  33. ^ Kahlert I; Brüne M. [A case of primary zopiclone dependence]. Dtsch Med Wochenschr. June 2001, 126 (22): 653–4. PMID 11450624. doi:10.1055/s-2001-14488. 
  34. ^ Professor Heather Ashton. BENZODIAZEPINES: HOW THEY WORK AND HOW TO WITHDRAW. 
  35. ^ Fontaine, R; Beaudry, P; Le, Morvan, P; Beauclair, L; Chouinard, G. Zopiclone and triazolam in insomnia associated with generalized anxiety disorder: a placebo-controlled evaluation of efficacy and daytime anxiety.. International clinical psychopharmacology (PDF). Jul 1990, 5 (3): 173–83. ISSN 0268-1315. PMID 2230061. doi:10.1097/00004850-199007000-00002. 
  36. ^ WHO. World Health Organisation - Assessment of Zopiclone (PDF). who.int. 2006. 
  37. ^ Kuitunen T; Mattila MJ; Seppala T. Actions and interactions of hypnotics on human performance: single doses of zopiclone, triazolam, and alcohol. Int Clin Psychopharmacol. April 1990, 5 (Suppl 2): 115–30. PMID 2201724. 
  38. ^ Parker, G; Roberts, Cj. Plasma concentrations and central nervous system effects of the new hypnotic agent zopiclone in patients with chronic liver disease.. British Journal of Clinical Pharmacology. Sep 1983, 16 (3): 259–65. ISSN 0306-5251. PMC 1428012. PMID 6626417. doi:10.1111/j.1365-2125.1983.tb02159.x. 
  39. ^ Tada, K; Sato, Y; Sakai, T; Ueda, N; Kasamo, K; Kojima, T. Effects of zopiclone, triazolam, and nitrazepam on standing steadiness.. Neuropsychobiology. 1994, 29 (1): 17–22. ISSN 0302-282X. PMID 8127419. doi:10.1159/000119057. 
  40. ^ Allain H, Bentué-Ferrer D, Tarral A, Gandon JM. Effects on postural oscillation and memory functions of a single dose of zolpidem 5 mg, zopiclone 3.75 mg and lormetazepam 1 mg in elderly healthy subjects. A randomized, cross-over, double-blind study versus placebo (PDF). Eur. J. Clin. Pharmacol. July 2003, 59 (3): 179–88. PMID 12756510. doi:10.1007/s00228-003-0591-5. 
  41. ^ Antai-Otong D. The art of prescribing. Risks and benefits of non-benzodiazepine receptor agonists in the treatment of acute primary insomnia in older adults. Perspect Psychiatr Care. August 2006, 42 (3): 196–200. PMID 16916422. doi:10.1111/j.1744-6163.2006.00070.x. [永久失效連結]
  42. ^ Upfal, Jonathan. The Australian Drug Guide 5. Melbourne: Bookman Press Pty Ltd. 2000: 743 [1991]. ISBN 1-86395-170-9. 
  43. ^ Cimolai N. Zopiclone: is it a pharmacologic agent for abuse?. Can Fam Physician. December 2007, 53 (12): 2124–9. PMC 2231551. PMID 18077750. 
  44. ^ Griffiths RR, Johnson MW. Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds. J Clin Psychiatry. 2005,. 66 Suppl 9: 31–41. PMID 16336040. 
  45. ^ Hoffmann F, Pfannkuche M, Glaeske G. [High usage of zolpidem and zopiclone. Cross-sectional study using claims data]. Nervenarzt. January 2008, 79 (1): 67–72. PMID 17457554. doi:10.1007/s00115-007-2280-6 (德语). 
  46. ^ Ströhle A, Antonijevic IA, Steiger A, Sonntag A. [Dependency of non-benzodiazepine hypnotics. Two case reports]. Nervenarzt. January 1999, 70 (1): 72–5. PMID 10087521. doi:10.1007/s001150050403 (德语). 
  47. ^ Kratzsch C, Tenberken O, Peters FT et al. Screening, library-assisted identification, and validated quantification of 23 benzodiazepines, flumazenil, zaleplone, zolpidem, and zopiclone in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization. J. Mass Spec. 39: 856-872, 2004.
  48. ^ Gustavsen I, Al-Sammurraie M, Mørland J, Bramness JG. Impairment related to blood drug concentrations of zopiclone and zolpidem compared with alcohol in apprehended drivers. Accid. Anal. Prev. 41: 462-466, 2009.
  49. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1677-1679.

外部連結[编辑]