血管紧张素 II (药物)

血管紧张素II
臨床資料
商品名（英语：Drug nomenclature）	Giapreza
AHFS/Drugs.com	Monograph
给药途径	Intravenous injection
藥物類別（英语：Drug class）	Vasoconstrictor
ATC碼	C01CX09 (WHO) ;
法律規範狀態
法律規範	歐：Rx-only; 美：处方药（℞-only）;
藥物動力學數據
血漿蛋白結合率	None
药物代谢	Proteolysis by glutamyl aminopeptidase, angiotensin converting enzyme 2
代謝產物	Angiotensin III, angiotensin-(1-7)
生物半衰期	Less than one minute (IV administration)
识别信息
	IUPAC命名法 L-alpha-aspartyl-L-arginyl-L-valyl-L-tyrosyl-L-isoleucyl-L-histidyl-L-prolyl-L-phenylalanine; ;
CAS号	4474-91-3
PubChem CID	172198;
DrugBank	DB11842;
ChemSpider	150504;
UNII	M089EFU921;
KEGG	D02014; as salt: D11142;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID30196288 ;
化学信息
化学式	C50H71N13O12
摩尔质量	1,046.20 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)O)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)O)N;
	InChI InChI=InChI=1S/C50H71N13O12/c1-5-28(4)41(47(72)59-36(23-31-25-54-26-56-31)48(73)63-20-10-14-38(63)45(70)60-37(49(74)75)22-29-11-7-6-8-12-29)62-44(69)35(21-30-15-17-32(64)18-16-30)58-46(71)40(27(2)3)61-43(68)34(13-9-19-55-50(52)53)57-42(67)33(51)24-39(65)66/h6-8,11-12,15-18,25-28,33-38,40-41,64H,5,9-10,13-14,19-24,51H2,1-4H3,(H,54,56)(H,57,67)(H,58,71)(H,59,72)(H,60,70)(H,61,68)(H,62,69)(H,65,66)(H,74,75)(H4,52,53,55)/t28-,33-,34-,35-,36-,37-,38-,40-,41-/m0/s1; Key:CZGUSIXMZVURDU-JZXHSEFVSA-N;

血管紧张素II（英語：Ang II）是一种用于治疗敗血性休克或其他分布性休克引起的低血壓药物。它是一种人工合成的血管收縮肽，与人体激素血管紧张素II^[3]相同，以Giapreza品牌销售。美国食品药品监督管理局于2017年12月批准使用血管紧张素II治疗敗血性休克引起的低血压。^[4]

美国食品药品监督管理局认定其为同类首创药物。^[5]

医疗用途

血管紧张素II是一种血管收縮剂，用于增加成人脓毒症或其他分布性休克患者的血压。血管紧张素II是一种天然激素，作为肾素-血管紧张素系统的一部分分泌，可导致强有力的全身性血管收缩。^[6]^[7]自20世纪30年代末首次分离出血管紧张素以来，人们一直在研究它的血管加压作用。^[8]血管加压药是指通过诱导外周血管收縮来对抗血管扩张性休克的药物。常用的血管加压剂包括儿茶酚胺类（如多巴胺、去甲肾上腺素、肾上腺素）和非儿茶酚胺（如抗利尿激素），但这些药物并非总能有效逆转血管舒张性休克，而且使用这些药物可能会产生明显的副作用，包括肢體缺血和心律不整。血管紧张素II是一种可增加血压并减少儿茶酚胺剂量的治疗选择。

血管紧张素II使用前必须以0.9%氯化钠稀释液靜脈注射。^[9]

不良反应

接受血管紧张素II治疗的患者发生血栓栓塞的风险增加。在ATHOS-3研究中，与接受安慰剂治疗的患者相比，接受血管紧张素II治疗的患者动脉和静脉血栓和血栓栓塞事件的发生率更高13%（21/163 例患者）对 5%（8/158 例患者）。^[10]建议患者同时进行静脉血栓栓塞预防。其他不良反应包括血小板减少、心跳过速、真菌感染、譫妄、酸中毒、高血糖和外周缺血。^[9]

血管紧张素II作用于突触前肾上腺素能神经上的血管紧张素受体（AT1）→释放儿茶酚胺→儿茶酚胺过多会导致肌细胞坏死，因而有害。^[11]

参考

^ 引用错误：没有为名为Giapreza FDA label的参考文献提供内容
^ Giapreza EPAR. European Medicines Agency. 23 August 2019 [13 June 2024].
^ Kaufman MB. Pharmaceutical Approval Update. P & T. March 2018, 43 (3): 141–170. PMC 5821238  . PMID 29491694.
^ FDA approves drug to treat dangerously low blood pressure (新闻稿). U.S. Food and Drug Administration (FDA). 21 December 2017.
^ New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (报告). January 2018 [16 September 2020].
^ Brown SM, Lanspa MJ, Jones JP, Kuttler KG, Li Y, Carlson R, Miller RR, Hirshberg EL, Grissom CK, Morris AH. Survival after shock requiring high-dose vasopressor therapy. Chest. March 2013, 143 (3): 664–671. PMC 3590882  . PMID 22911566. doi:10.1378/chest.12-1106.
^ Chawla LS, Busse L, Brasha-Mitchell E, Davison D, Honiq J, Alotaibi Z, Seneff MG. Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Critical Care. October 2014, 18 (5): 534. PMC 4212099  . PMID 25286986. doi:10.1186/s13054-014-0534-9  .
^ Bradley SE, Parker B. The Hemodynamic Effects of Angiotonin in Normal Man. The Journal of Clinical Investigation. November 1941, 20 (6): 715–719. PMC 435102  . PMID 16694877. doi:10.1172/JCI101265.
^ ^9.0 ^9.1 Giapreza- angiotensin ii injection. DailyMed. 20 June 2020 [17 September 2020].
^ Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hästbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Deane AM. Angiotensin II for the Treatment of Vasodilatory Shock. The New England Journal of Medicine. August 2017, 377 (5): 419–430. PMID 28528561. S2CID 205102054. doi:10.1056/NEJMoa1704154  . hdl:1959.13/1353018  .
^ Liaudet L, Calderari B, Pacher P. Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity (PDF). Heart Failure Reviews. November 2014, 19 (6): 815–824. PMID 24398587. S2CID 22420796. doi:10.1007/s10741-014-9418-y.

[Giapreza_FDA_label-1] 引用错误：没有为名为Giapreza FDA label的参考文献提供内容

[Giapreza_EPAR-2] Giapreza EPAR. European Medicines Agency. 23 August 2019 [13 June 2024].

[Kaufman_20182-3] Kaufman MB. Pharmaceutical Approval Update. P & T. March 2018, 43 (3): 141–170. PMC 5821238  . PMID 29491694.

[4] FDA approves drug to treat dangerously low blood pressure (新闻稿). U.S. Food and Drug Administration (FDA). 21 December 2017.

[5] New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (报告). January 2018 [16 September 2020].

[6] Brown SM, Lanspa MJ, Jones JP, Kuttler KG, Li Y, Carlson R, Miller RR, Hirshberg EL, Grissom CK, Morris AH. Survival after shock requiring high-dose vasopressor therapy. Chest. March 2013, 143 (3): 664–671. PMC 3590882  . PMID 22911566. doi:10.1378/chest.12-1106.

[7] Chawla LS, Busse L, Brasha-Mitchell E, Davison D, Honiq J, Alotaibi Z, Seneff MG. Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Critical Care. October 2014, 18 (5): 534. PMC 4212099  . PMID 25286986. doi:10.1186/s13054-014-0534-9  .

[8] Bradley SE, Parker B. The Hemodynamic Effects of Angiotonin in Normal Man. The Journal of Clinical Investigation. November 1941, 20 (6): 715–719. PMC 435102  . PMID 16694877. doi:10.1172/JCI101265.

[Giapreza_FDA_label2-9] 9.0 ^9.1 Giapreza- angiotensin ii injection. DailyMed. 20 June 2020 [17 September 2020].

[10] Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hästbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Deane AM. Angiotensin II for the Treatment of Vasodilatory Shock. The New England Journal of Medicine. August 2017, 377 (5): 419–430. PMID 28528561. S2CID 205102054. doi:10.1056/NEJMoa1704154  . hdl:1959.13/1353018  .

[11] Liaudet L, Calderari B, Pacher P. Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity (PDF). Heart Failure Reviews. November 2014, 19 (6): 815–824. PMID 24398587. S2CID 22420796. doi:10.1007/s10741-014-9418-y.

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