异氟烷

异氟烷
临床资料
商品名（英语：Drug nomenclature）	Forane及其他
AHFS/Drugs.com	FDA专业药物信息
核准状况	美 DailyMed: Isoflurane;
怀孕分级	澳: B3 ; ;
给药途径	吸入
ATC码	N01AB06 (WHO) ;
法律规范状态
法律规范	英：处方药（℞-only） (POM); 美：处方药（℞-only）;
识别信息
	IUPAC命名法 (RS)-2-Chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane; OR; (RS)-1-chloro-2,2,2-trifluoroethyl difluoromethyl ether; ;
CAS号	26675-46-7
PubChem CID	3763;
IUPHAR/BPS	2505;
DrugBank	DB00753 ;
ChemSpider	3631 ;
UNII	CYS9AKD70P;
KEGG	D00545 ;
ChEBI	CHEBI:6015 ;
ChEMBL	ChEMBL1256 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID3020752 ;
ECHA InfoCard	100.043.528
化学信息
化学式	C3H2ClF5O
摩尔质量	184.49 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES FC(F)(F)C(Cl)OC(F)F;
	InChI InChI=1S/C3H2ClF5O/c4-1(3(7,8)9)10-2(5)6/h1-2H ; Key:PIWKPBJCKXDKJR-UHFFFAOYSA-N ;

异氟烷^[5]^[6]（INN：isoflurane）或称异氟醚，常见商品名Forane，是人畜常用的挥发性吸入全身麻醉药，可用于诱导或维持全身麻醉^[7]。

异氟烷为恩氟烷（enflurane）的同分异构体，作用与恩氟烷相似，理化性质比恩氟烷稳定，但对呼吸道有刺激性，可引起咳嗽、屏气等。麻醉时对呼吸循环系统的抑制作用较深，骨骼肌松弛作用较完全。对呼吸的抑制作用与剂量有关。适用于癫痫、颅内压增高者。

受制于异氟烷对气管的刺激性，目前可有其他药物的选择以进行诱导麻醉^[8]^[9]。异氟烷的给药方式为吸入其蒸气^[7]。

异氟烷的副作用包括抑制呼吸中枢、降低血压及导致心律不齐^[8]。更为严重的副作用包括恶性高热及高血钾症^[7]。异氟烷不宜在本人或家族有恶性高热病史的情况下使用^[8]。个体于怀孕期间使用本药对胎儿的安全性目前不明，但在剖腹生产的情况下使用相信是安全的^[7]^[8]。

异氟烷是卤代醚（英语：Halogenated ether）麻醉药家族的一员^[10]，在美国于1979年首次获准临床使用^[7]。异氟烷是世界卫生组织基本药物标准清单中的药品，是基础医疗系统必备的药品之一^[11]。本药在发展中国家售价约为每瓶（250毫升）17至170美元^[12]。

医疗用途

异氟烷给药时，通常会与空气或纯氧混合，有时也会额外加上一氧化二氮。虽然异氟烷的物理特性可诱导麻醉的速度比氟烷更快^[13]，但因它对呼吸道具刺激性，而抵销其物理特性带来的潜在优势。异氟烷主要作为全身麻醉的维持药物，在先使用硫喷妥钠或异丙酚等静脉注射药物诱导麻醉后，再行使用^[14]^[15]^[16]。

作用机理

异氟烷和其他全身麻醉药一样，确实作用机理仍有待进一步探讨^[17]。异氟烷可以减低对痛楚的敏感度并松弛肌肉。本药可与GABA受体、谷氨酸受体及甘氨酸受体、ATP合成酶的亚单位D及NADH脱氢酶结合，但对每种蛋白质的作用各有不同。异氟烷能激活谷氨酸受体、甘氨酸受体及GABA受体的活动，而后两者会导致运动功能压抑^[18]。相反，异氟烷对已打开的钾离子通道的传导有压抑作用^[19]。

透过异氟烷施行的全身麻醉会减低血浆的花生四烯酸乙醇胺（一种内源性大麻素（英语：endocannabinoid system））浓度。这也许和全身麻醉后压力水平降低有关^[20]。

副作用

异氟烷会引起使用者血压突然下降，原因为有剂量依赖性的周边血管扩张所致。此情况在低血容量患者中会特别明显^[16]。

动物实验显示，某些全身麻醉药物，尤其是氯胺酮和异氟烷，在幼儿身上使用时可能存在安全疑虑。若这些药物与一氧化二氮及苯二氮平类药物（如咪达唑仑）并用，则神经退化的风险会增加^[21]。然而，这些疑虑是否适用于人类，目前仍不清楚^[21]。

老年人

使用核磁共振波谱学的生物物理学研究，提供吸入性麻醉剂如何与淀粉样β肽的三个氨基酸残基（G29、A30和I31）交互作用，并诱导聚集的分子细节^[22]。由于这些吸入性麻醉剂可能会加速阿兹海默氏病的进程，因而此项研究相当重要^[23]。

特性

分子质量：184.5克/摩尔^[24]
沸点（大气压力下）：48.5°C^[24]
密度（25℃）：1.496克/毫升^[24]
最低气泡浓度（英语：Minimum alveolar concentration）：1.17%^[25]^{[注 1]}
蒸气压^[24]：
- 238mmHg 31.7kPa（20℃）
- 295 mmHg 39.3 kPa（25°C）
- 367mmHg 48.9kPa（30℃）
- 450mmHg 60.0kPa（35℃）
水溶解度（25℃）：13.5 mM^[26]
$\log {K_{ow}}$ ：2.06^[24]^{[注 2]}

异氟烷以(R)-和(S)-光学异构体的消旋混合物形式给药^[27]。异氟烷的沸点为48.5–49°C（119.3–120.2°F）。^[28]它不可燃，但暴露于火焰时会释放出刺激性和有毒的烟雾^[28]。

历史

在1940年代至1950年代，异氟烷、恩氟醚和氟烷等新型吸入性麻醉剂相继问世，逐步取代具有易燃性和其他潜在的副作用的乙醚^[29]。异氟烷（isoflurane）名称源于它是恩氟醚（enflurane）的结构异构体，两者具有相同的实验式^[30]。

环境影响

异氟烷每年因医疗麻醉用途而释放到大气中的总量约为880吨，平均寿命约为3.2年。由于其全球暖化潜势高达510，相当于不小数量二氧化碳的排放，对气候变化有不可忽视的影响^[31]。

兽医用途

异氟烷经常于进行兽医麻醉（英语：veterinary anaesthesia）时使用^[32]^[33]。

参考文献

^ Isoflurane Use During Pregnancy. Drugs.com. 2020-09-02 [9 September 2020-09-09].
^ Isoflurane 100% Inhalation Vapour, Liquid - Summary of Product Characteristics (SmPC). (emc). 2019-10-29 [9 September 2020-09-09].
^ Forane- isoflurane inhalant. DailyMed. [2022-02-11].
^ Anvisa. RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control]. Diário Oficial da União. 2023-03-31 (2023-04-04) [2023-08-16]. （原始内容存档于2023-08-03）（巴西葡萄牙语）.
^ 异氟烷. 术语在线. 全国科学技术名词审定委员会. （简体中文）
^ 王波云; 李菊相. 兒科藥物速查手冊. 河北科学技术出版社. 2004: 365. ISBN 9787537527620.
^ ^7.0 ^7.1 ^7.2 ^7.3 ^7.4 Isoflurane - FDA prescribing information, side effects and uses. www.drugs.com. March 2015 [2016-12-13]. （原始内容存档于2016-12-21）.
^ ^8.0 ^8.1 ^8.2 ^8.3 Isoflurane (inhalation anaesthetic) - Summary of Product Characteristics (SPC) - (eMC). www.medicines.org.uk. 2016-01-11 [2016-12-13]. （原始内容存档于2016-12-20）.
^ Kliegman, Robert M.; Stanton, Bonita M. D.; Geme, Joseph St; Schor, Nina F. Nelson Textbook of Pediatrics 20. Elsevier Health Sciences. 2015: 420 [2017-06-26]. ISBN 9780323263528. （原始内容存档于2016-12-20）（英语）.
^ Aglio, Linda S.; Lekowski, Robert W.; Urman, Richard D. Essential Clinical Anesthesia Review: Keywords, Questions and Answers for the Boards. Cambridge University Press. 2015: 115 [2017-06-26]. ISBN 9781107681309. （原始内容存档于2016-12-20）（英语）.
^ WHO Model List of Essential Medicines (19th List) (PDF). World Health Organization. April 2015 [2016-12-08]. （原始内容存档 (PDF)于2016-12-13）.
^ Isoflurane. International Drug Price Indicator Guide. [2016-12-08]. ^{[永久失效链接]}
^ Niedermeyer E, da Silva FH. Electroencephalography: Basic Principles, Clinical Applications, and Related Fields. Lippincott Williams & Wilkins. 2005: 1156. ISBN 978-0-7817-5126-1. （原始内容存档于2016-05-09）.
^ Pauca AL, Dripps RD. Clinical experience with isoflurane (Forane): preliminary communication. British Journal of Anaesthesia. July 1973, 45 (7): 697–703. PMID 4730162. doi:10.1093/bja/45.7.697 .
^ Chen Z. The effects of isoflurane and propofol on intraoperative neurophysiological monitoring during spinal surgery. Journal of Clinical Monitoring and Computing. August 2004, 18 (4): 303–308. PMID 15779842. S2CID 195331061. doi:10.1007/s10877-005-5097-5.
^ ^16.0 ^16.1 Hawkley TF, Preston M, Maani CV. Isoflurane. StatPearls. 2022. PMID 30422552.
^ How does anesthesia work?. Scientific American. 2005-02-07 [2017-06-26]. （原始内容存档于2016-05-29）.
^ Grasshoff, C.; Antkowiak, B. Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats (PDF). British Journal of Anaesthesia. 2006-09-13, 97 (5): 687–694 [2017-06-28]. ISSN 0007-0912. doi:10.1093/bja/ael239. （原始内容存档 (PDF)于2017-09-10）（英语）.
^ Buljubasic, N.; Rusch, NJ.; Marijic, J; Kampine; ZJ, Bosnjak. Effects of halothane and isoflurane on calcium and potassium channel currents in canine coronary arterial cells. Anaesthesiology: 990–998. [2017-06-28]. PMID 1318010. （原始内容存档于2017-09-10）（英语）.
^ Weis, F.; Beiras-Fernandez, A.; Hauer, D.; Hornuss, C.; Sodian, R.; Kreth, S.; Briegel, J.; Schelling, G. Effect of anaesthesia and cardiopulmonary bypass on blood endocannabinoid concentrations during cardiac surgery. British Journal of Anaesthesia. 2010-08-01, 105 (2): 139–144 [2017-06-26]. ISSN 0007-0912. PMID 20525978. doi:10.1093/bja/aeq117. （原始内容存档于2021-08-28）（英语）.
^ ^21.0 ^21.1 Mellon RD, Simone AF, Rappaport BA. Use of anesthetic agents in neonates and young children. Anesthesia and Analgesia. March 2007, 104 (3): 509–520. PMID 17312200. S2CID 43818997. doi:10.1213/01.ane.0000255729.96438.b0 . （原始内容存档于2009-03-09）.
^ Mandal, et al. Isoflurane and desflurane at clinically relevant concentrations induce amyloid b-peptide oligomerization: An NMR study. Biochemical and Biophysical Research Communications. April 2009, 379 (3): 716–720. PMID 19116131. doi:10.1016/j.bbrc.2008.12.092.
^ Kuehn BM. Anesthesia-Alzheimer disease link probed. JAMA. April 2007, 297 (16): 1760. PMID 17456811. doi:10.1001/jama.297.16.1760.
^ ^24.0 ^24.1 ^24.2 ^24.3 ^24.4 Record of Isofluran in the GESTIS Substance Database from the IFA（英语：Institute for Occupational Safety and Health）.
^ Nickalls, R. W. D., & Mapleson, W. W. Age-related iso-MAC charts for isoflurane, sevoflurane, and desflurane in man. British Journal of Anaesthesia. August 2003, 91 (2): 170–4 [2017-06-26]. PMID 12878613. doi:10.1093/bja/aeg132. （原始内容存档于2013-04-15）（英语）.
^ Seto, T; Mashimo, T; Yoshiya, I; Kanashiro, M; Taniguchi, Y, The solubility of volatile anaesthetics in water at 25.0 degrees C using 19F NMR spectroscopy., J Pharm Biomed Anal, 1992, 10: 1–7, PMID 1391078
^ Bu W, Pereira LM, Eckenhoff RG, Yuki K. Stereoselectivity of isoflurane in adhesion molecule leukocyte function-associated antigen-1. PLOS ONE. 2014-05-06, 9 (5): e96649. Bibcode:2014PLoSO...996649B. PMC 4011845 . PMID 24801074. doi:10.1371/journal.pone.0096649 .
^ ^28.0 ^28.1 Isoflurane. PubChem. U.S. National Library of Medicine. [2022-04-07] （英语）.
^ Terrell RC. The invention and development of enflurane, isoflurane, sevoflurane, and desflurane. Anesthesiology. March 2008, 108 (3): 531–533. PMID 18292690. doi:10.1097/ALN.0b013e31816499cc .
^ Calvey TN. Isomerism and anaesthetic drugs. Acta Anaesthesiologica Scandinavica. Supplementum. August 1995, 106: 83–90. PMID 8533553. S2CID 24183480. doi:10.1111/j.1399-6576.1995.tb04316.x.
^ Martin K. Vollmer; Tae Siek Rhee; Matt Rigby; Doris Hofstetter; Matthias Hill; Fabian Schoenenberger; Stefan Reimann. Modern inhalation anesthetics: Potent greenhouse gases in the global atmosphere. Geophysical Research Letters. 2015, 42 (5): 1606–1611. doi:10.1002/2014GL062785.
^ Ludders JW. Advantages and guidelines for using isoflurane. The Veterinary Clinics of North America. Small Animal Practice. March 1992, 22 (2): 328–331. PMID 1585568. doi:10.1016/s0195-5616(92)50626-x .
^ Isoflurane-Vet 100% w/w Inhalation vapour, liquid. www.noahcompendium.co.uk. [2022-04-07] （英语）.

外部链接

Isoflurane. Drug Information Portal. U.S. National Library of Medicine.
美国专利第3,535,388号 - 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether
美国专利第3,535,425号 - 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether as an anesthetic agent

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引用错误：页面中存在<ref group="註">标签，但没有找到相应的<references group="註" />标签

[Drugs.com_pregnancy-1] Isoflurane Use During Pregnancy. Drugs.com. 2020-09-02 [9 September 2020-09-09].

[Isoflurane_SmPC-2] Isoflurane 100% Inhalation Vapour, Liquid - Summary of Product Characteristics (SmPC). (emc). 2019-10-29 [9 September 2020-09-09].

[Forane_FDA_label-3] Forane- isoflurane inhalant. DailyMed. [2022-02-11].

[4] Anvisa. RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control]. Diário Oficial da União. 2023-03-31 (2023-04-04) [2023-08-16]. （原始内容存档于2023-08-03）（巴西葡萄牙语）.

[5] 异氟烷. 术语在线. 全国科学技术名词审定委员会. （简体中文）

[6] 王波云; 李菊相. 兒科藥物速查手冊. 河北科学技术出版社. 2004: 365. ISBN 9787537527620.

[Pro2015-7] 7.0 ^7.1 ^7.2 ^7.3 ^7.4 Isoflurane - FDA prescribing information, side effects and uses. www.drugs.com. March 2015 [2016-12-13]. （原始内容存档于2016-12-21）.

[EMC2016-8] 8.0 ^8.1 ^8.2 ^8.3 Isoflurane (inhalation anaesthetic) - Summary of Product Characteristics (SPC) - (eMC). www.medicines.org.uk. 2016-01-11 [2016-12-13]. （原始内容存档于2016-12-20）.

[9] Kliegman, Robert M.; Stanton, Bonita M. D.; Geme, Joseph St; Schor, Nina F. Nelson Textbook of Pediatrics 20. Elsevier Health Sciences. 2015: 420 [2017-06-26]. ISBN 9780323263528. （原始内容存档于2016-12-20）（英语）.

[10] Aglio, Linda S.; Lekowski, Robert W.; Urman, Richard D. Essential Clinical Anesthesia Review: Keywords, Questions and Answers for the Boards. Cambridge University Press. 2015: 115 [2017-06-26]. ISBN 9781107681309. （原始内容存档于2016-12-20）（英语）.

[WHO19th-11] WHO Model List of Essential Medicines (19th List) (PDF). World Health Organization. April 2015 [2016-12-08]. （原始内容存档 (PDF)于2016-12-13）.

[ERC2014-12] Isoflurane. International Drug Price Indicator Guide. [2016-12-08]. ^{[永久失效链接]}

[NiedermeyerSilva2005-13] Niedermeyer E, da Silva FH. Electroencephalography: Basic Principles, Clinical Applications, and Related Fields. Lippincott Williams & Wilkins. 2005: 1156. ISBN 978-0-7817-5126-1. （原始内容存档于2016-05-09）.

[14] Pauca AL, Dripps RD. Clinical experience with isoflurane (Forane): preliminary communication. British Journal of Anaesthesia. July 1973, 45 (7): 697–703. PMID 4730162. doi:10.1093/bja/45.7.697 .

[15] Chen Z. The effects of isoflurane and propofol on intraoperative neurophysiological monitoring during spinal surgery. Journal of Clinical Monitoring and Computing. August 2004, 18 (4): 303–308. PMID 15779842. S2CID 195331061. doi:10.1007/s10877-005-5097-5.

[NBK532957-16] 16.0 ^16.1 Hawkley TF, Preston M, Maani CV. Isoflurane. StatPearls. 2022. PMID 30422552.

[17] How does anesthesia work?. Scientific American. 2005-02-07 [2017-06-26]. （原始内容存档于2016-05-29）.

[18] Grasshoff, C.; Antkowiak, B. Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats (PDF). British Journal of Anaesthesia. 2006-09-13, 97 (5): 687–694 [2017-06-28]. ISSN 0007-0912. doi:10.1093/bja/ael239. （原始内容存档 (PDF)于2017-09-10）（英语）.

[19] Buljubasic, N.; Rusch, NJ.; Marijic, J; Kampine; ZJ, Bosnjak. Effects of halothane and isoflurane on calcium and potassium channel currents in canine coronary arterial cells. Anaesthesiology: 990–998. [2017-06-28]. PMID 1318010. （原始内容存档于2017-09-10）（英语）.

[20] Weis, F.; Beiras-Fernandez, A.; Hauer, D.; Hornuss, C.; Sodian, R.; Kreth, S.; Briegel, J.; Schelling, G. Effect of anaesthesia and cardiopulmonary bypass on blood endocannabinoid concentrations during cardiac surgery. British Journal of Anaesthesia. 2010-08-01, 105 (2): 139–144 [2017-06-26]. ISSN 0007-0912. PMID 20525978. doi:10.1093/bja/aeq117. （原始内容存档于2021-08-28）（英语）.

[Mel2007-21] 21.0 ^21.1 Mellon RD, Simone AF, Rappaport BA. Use of anesthetic agents in neonates and young children. Anesthesia and Analgesia. March 2007, 104 (3): 509–520. PMID 17312200. S2CID 43818997. doi:10.1213/01.ane.0000255729.96438.b0 . （原始内容存档于2009-03-09）.

[Mandal-2009-22] Mandal, et al. Isoflurane and desflurane at clinically relevant concentrations induce amyloid b-peptide oligomerization: An NMR study. Biochemical and Biophysical Research Communications. April 2009, 379 (3): 716–720. PMID 19116131. doi:10.1016/j.bbrc.2008.12.092.

[Kuehn-2007-23] Kuehn BM. Anesthesia-Alzheimer disease link probed. JAMA. April 2007, 297 (16): 1760. PMID 17456811. doi:10.1001/jama.297.16.1760.

[GESTIS-24] 24.0 ^24.1 ^24.2 ^24.3 ^24.4 Record of Isofluran in the GESTIS Substance Database from the IFA（英语：Institute for Occupational Safety and Health）.

[MAC-25] Nickalls, R. W. D., & Mapleson, W. W. Age-related iso-MAC charts for isoflurane, sevoflurane, and desflurane in man. British Journal of Anaesthesia. August 2003, 91 (2): 170–4 [2017-06-26]. PMID 12878613. doi:10.1093/bja/aeg132. （原始内容存档于2013-04-15）（英语）.

[27] Seto, T; Mashimo, T; Yoshiya, I; Kanashiro, M; Taniguchi, Y, The solubility of volatile anaesthetics in water at 25.0 degrees C using 19F NMR spectroscopy., J Pharm Biomed Anal, 1992, 10: 1–7, PMID 1391078

[29] Bu W, Pereira LM, Eckenhoff RG, Yuki K. Stereoselectivity of isoflurane in adhesion molecule leukocyte function-associated antigen-1. PLOS ONE. 2014-05-06, 9 (5): e96649. Bibcode:2014PLoSO...996649B. PMC 4011845 . PMID 24801074. doi:10.1371/journal.pone.0096649 .

[:0-30] 28.0 ^28.1 Isoflurane. PubChem. U.S. National Library of Medicine. [2022-04-07] （英语）.

[31] Terrell RC. The invention and development of enflurane, isoflurane, sevoflurane, and desflurane. Anesthesiology. March 2008, 108 (3): 531–533. PMID 18292690. doi:10.1097/ALN.0b013e31816499cc .

[32] Calvey TN. Isomerism and anaesthetic drugs. Acta Anaesthesiologica Scandinavica. Supplementum. August 1995, 106: 83–90. PMID 8533553. S2CID 24183480. doi:10.1111/j.1399-6576.1995.tb04316.x.

[33] Martin K. Vollmer; Tae Siek Rhee; Matt Rigby; Doris Hofstetter; Matthias Hill; Fabian Schoenenberger; Stefan Reimann. Modern inhalation anesthetics: Potent greenhouse gases in the global atmosphere. Geophysical Research Letters. 2015, 42 (5): 1606–1611. doi:10.1002/2014GL062785.

[34] Ludders JW. Advantages and guidelines for using isoflurane. The Veterinary Clinics of North America. Small Animal Practice. March 1992, 22 (2): 328–331. PMID 1585568. doi:10.1016/s0195-5616(92)50626-x .

[35] Isoflurane-Vet 100% w/w Inhalation vapour, liquid. www.noahcompendium.co.uk. [2022-04-07] （英语）.

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[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[注 1]

[26]

[注 2]

[27]

[28]

[29]

[30]

[31]

[32]

[33]