血管緊張素 II (藥物)

血管緊張素II
臨床資料
商品名（英語：Drug nomenclature）	Giapreza
AHFS/Drugs.com	Monograph
給藥途徑	Intravenous injection
藥物類別（英語：Drug class）	Vasoconstrictor
ATC碼	C01CX09 (WHO) ;
法律規範狀態
法律規範	歐：Rx-only; 美：處方藥（℞-only）;
藥物動力學數據
血漿蛋白結合率	None
藥物代謝	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)
識別資訊
	IUPAC命名法 L-alpha-aspartyl-L-arginyl-L-valyl-L-tyrosyl-L-isoleucyl-L-histidyl-L-prolyl-L-phenylalanine; ;
CAS號	4474-91-3
PubChem CID	172198;
DrugBank	DB11842;
ChemSpider	150504;
UNII	M089EFU921;
KEGG	D02014; as salt: D11142;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID30196288 ;
化學資訊
化學式	C50H71N13O12
摩爾質量	1,046.20 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
	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;

血管緊張素II（英語：Ang II）是一種用於治療敗血性休克或其他分佈性休克引起的低血壓藥物。它是一種人工合成的血管收縮肽，與人體激素血管緊張素II^[3]相同，以Giapreza品牌銷售。美國食品藥品監督管理局於2017年12月批准使用血管緊張素II治療敗血性休克引起的低血壓。^[4]

美國食品藥品監督管理局認定其為同類首創藥物。^[5]

醫療用途

血管緊張素II是一種血管收縮劑，用於增加成人膿毒症或其他分佈性休克患者的血壓。血管緊張素II是一種天然激素，作為腎素-血管緊張素系統的一部分分泌，可導致強有力的全身性血管收縮。^[6]^[7]自20世紀30年代末首次分離出血管緊張素以來，人們一直在研究它的血管加壓作用。^[8]血管加壓藥是指通過誘導外周血管收縮來對抗血管擴張性休克的藥物。常用的血管加壓劑包括兒茶酚胺類（如多巴胺、去甲腎上腺素、腎上腺素）和非兒茶酚胺（如抗利尿激素），但這些藥物並非總能有效逆轉血管舒張性休克，而且使用這些藥物可能會產生明顯的副作用，包括肢體缺血和心律不整。血管緊張素II是一種可增加血壓並減少兒茶酚胺劑量的治療選擇。

血管緊張素II使用前必須以0.9%氯化鈉稀釋液靜脈注射。^[9]

不良反應

接受血管緊張素II治療的患者發生血栓栓塞的風險增加。在ATHOS-3研究中，與接受安慰劑治療的患者相比，接受血管緊張素II治療的患者動脈和靜脈血栓和血栓栓塞事件的發生率更高13%（21/163 例患者）對 5%（8/158 例患者）。^[10]建議患者同時進行靜脈血栓栓塞預防。其他不良反應包括血小板減少、心跳過速、真菌感染、譫妄、酸中毒、高血糖和外周缺血。^[9]

血管緊張素II作用於突觸前腎上腺素能神經上的血管緊張素受體（AT1）→釋放兒茶酚胺→兒茶酚胺過多會導致肌細胞壞死，因而有害。^[11]

參考

^ 引用錯誤：沒有為名為Giapreza FDA label的參考文獻提供內容
^ 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 (新聞稿). U.S. Food and Drug Administration (FDA). 21 December 2017.
^ New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (報告). 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] 引用錯誤：沒有為名為Giapreza FDA label的參考文獻提供內容

[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 (新聞稿). U.S. Food and Drug Administration (FDA). 21 December 2017.

[5] New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (報告). 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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