二氮嗪
二氮嗪(英语:Diazoxide)以Proglycem等品牌于市面上销售,是一种用于治疗多种特定原因引起的低血糖药物,[2]包括无法切除的胰神经内分泌瘤和枫香氨酸敏感性婴儿低血糖症。[2]也可用于治疗难治性磺酰脲类中毒。[3]一般采口服方式给药。[2]
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临床资料 | |
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商品名 | Proglycem |
AHFS/Drugs.com | Monograph |
核准状况 | |
怀孕分级 |
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给药途径 | 口服给药, 静脉注射 |
ATC码 | |
法律规范状态 | |
法律规范 |
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药物动力学数据 | |
血浆蛋白结合率 | 90% |
药物代谢 | 肝脏 氧化及硫酸盐偶联 |
生物半衰期 | 21-45小时 |
排泄途径 | 肾脏 |
识别信息 | |
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CAS号 | 364-98-7 ![]() |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.006.063 |
化学信息 | |
化学式 | C8H7ClN2O2S |
摩尔质量 | 230.67 g·mol−1 |
3D模型(JSmol) | |
熔点 | 330至331 °C(626至628 °F) |
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使用后常见的副作用有高血糖、水肿、血小板减少症、心率加快、毛发生长加快和恶心。[3]其他严重的副作用有肺高压和心脏衰竭。[3]此药物的化学性质与噻嗪类利尿剂相似,[3]透过减少胰脏的胰岛素释放和增加肝脏的葡萄糖释放而发挥作用。[3]
二氮嗪于1973年被美国食品药物管理局(FDA)批准用于医疗用途。[3]它已被列入世界卫生组织基本药物标准清单之中。[4][5]市面上有其通用名药物流通。[6]
FDA将二氮嗪列为怀孕安全等级C类药物(动物实验存在潜在风险、缺乏人类临床试验数据及虽然存在潜在风险,但在某些特定情况下,药物治疗益处可能大于对胎儿的潜潜在危害。医生会权衡利弊后决定是否用药。)。在动物的繁殖研究显示该药物对多个胎儿组织(包括骨骼和心脏组织)具有毒性和致畸型性。二氮嗪可穿越动物的胎盘,导致胎儿胰脏的β细胞退化。但目前尚未确定此药物在人类怀孕期间的安全性。然而孕妇暴露于该药物可能会导致新生儿黄疸、血小板减少症以及碳水化合物代谢紊乱(包括脱发和先天性遗传多毛症)。哺乳期妇女在服用此药物之前应谘询医生。[7]
医疗用途
编辑二氮嗪是种血管舒张剂,用于治疗急性高血压或严重高血压。[8]
此药物也透过打开胰脏β细胞的ATP敏感钾通道来抑制胰岛素分泌。它因此可用于对抗胰岛素瘤(产生胰岛素的肿瘤)[9]或先天性高胰岛素血症等疾病而发生的低血糖。
副作用
编辑二氮嗪透过其对钾通道的作用而干扰胰岛素释放。[11]二氮嗪是胰脏中产生胰岛素的β细胞上的ATP钾通道最有效的开放剂之一。打开这些通道会导致细胞膜超极化,钙流入减少,随后胰岛素释放减少。[3]这种作用机转与磺酰脲类药物的作用机转相反,磺酰脲类药物是一类用于增加第2型糖尿病患者胰岛素释放的药物。此药物因此不适合第2型糖尿病患者服用。
FDA于2015年7月发布一项安全通告,强调使用该药物治疗的新生儿和婴儿可能会出现肺高压。[12]
禁忌症
编辑包括如下:[13]
与其他药物交互作用
编辑一般而言,二氮嗪与其他药物没严重的交互作用。[14]
合成
编辑研究
编辑由二氮氧化物和氯化胆碱组成的二氮嗪正被作为一种实验性抗肥胖药物,为患有普瑞德威利症候群[[15][16][17]和由SH2B1、PCSK1或SIM1基因突变所引起的单基因肥胖症患者中进行测试。[18]
参考文献
编辑- ^ Product monograph brand safety updates. Health Canada. 2016-07-06 [2024-04-03].
- ^ 2.0 2.1 2.2 Diazoxide Monograph for Professionals. Drugs.com. [11 October 2019] (英语).
- ^ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Doyle ME, Egan JM. Pharmacological agents that directly modulate insulin secretion. Pharmacological Reviews. March 2003, 55 (1): 105–131. PMID 12615955. S2CID 11121340. doi:10.1124/pr.55.1.7.
- ^ World Health Organization. World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. hdl:10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^ World Health Organization. World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. 2021. hdl:10665/345533 . WHO/MHP/HPS/EML/2021.02.
- ^ British national formulary : BNF 76 76. Pharmaceutical Press. 2018: 708. ISBN 9780857113382.
- ^ Farris, F.F. Encyclopedia of Toxicology Reference Work • Third Edition • 2014 https://www.sciencedirect.com/topics/chemistry/diazoxide. [20240702]. 缺少或
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为空 (帮助) - ^ van Hamersvelt HW, Kloke HJ, de Jong DJ, Koene RA, Huysmans FT. Oedema formation with the vasodilators nifedipine and diazoxide: direct local effect or sodium retention?. Journal of Hypertension. August 1996, 14 (8): 1041–1045. PMID 8884561. S2CID 3283469. doi:10.1097/00004872-199608000-00016.
- ^ Huang Q, Bu S, Yu Y, Guo Z, Ghatnekar G, Bu M, Yang L, Lu B, Feng Z, Liu S, Wang F. Diazoxide prevents diabetes through inhibiting pancreatic beta-cells from apoptosis via Bcl-2/Bax rate and p38-beta mitogen-activated protein kinase. Endocrinology. January 2007, 148 (1): 81–91. PMID 17053028. doi:10.1210/en.2006-0738 .
- ^ Randle JC, Biton C, Lepagnol JM. Allosteric potentiation by diazoxide of AMPA receptor currents and synaptic potentials. European Journal of Pharmacology. November 1993, 247 (3): 257–265. PMID 8307099. doi:10.1016/0922-4106(93)90193-D.
- ^ Panten U, Burgfeld J, Goerke F, Rennicke M, Schwanstecher M, Wallasch A, Zünkler BJ, Lenzen S. Control of insulin secretion by sulfonylureas, meglitinide and diazoxide in relation to their binding to the sulfonylurea receptor in pancreatic islets. Biochemical Pharmacology. April 1989, 38 (8): 1217–1229. PMID 2650685. doi:10.1016/0006-2952(89)90327-4.
- ^ FDA Drug Safety Communication: FDA warns about a serious lung condition in infants and newborns treated with Proglycem (diazoxide) (新闻稿). Food and Drug Administration. 2015-07-16 [2015-07-19].
- ^ Diazoxide. Padiatric Oncall. [2024-07-02].
- ^ 14.0 14.1 14.2 DIAZOXIDE. RxList. [2024-07-02].
- ^ Miller JL, Gevers E, Bridges N, Yanovski JA, Salehi P, Obrynba KS, Felner EI, Bird LM, Shoemaker AH, Angulo M, Butler MG, Stevenson D, Goldstone AP, Wilding J, Lah M, Shaikh MG, Littlejohn E, Abuzzahab MJ, Fleischman A, Hirano P, Yen K, Cowen NM, Bhatnagar A. Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study. Obesity. February 2024, 32 (2): 252–261. PMID 37919617. S2CID 264973612. doi:10.1002/oby.23928 . hdl:10044/1/107689 .
- ^ Kimonis V, Surampalli A, Wencel M, Gold JA, Cowen NM. A randomized pilot efficacy and safety trial of diazoxide choline controlled-release in patients with Prader-Willi syndrome. PLOS ONE. 23 September 2019, 14 (9): e0221615. Bibcode:2019PLoSO..1421615K. PMC 6756513 . PMID 31545799. doi:10.1371/journal.pone.0221615 .
- ^ Miller JL, Gevers E, Bridges N, Yanovski JA, Salehi P, Obrynba KS, Felner EI, Bird LM, Shoemaker AH, Angulo M, Butler MG, Stevenson D, Abuzzahab J, Barrett T, Lah M, Littlejohn E, Mathew V, Cowen NM, Bhatnagar A. Diazoxide Choline Extended-Release Tablet in People With Prader-Willi Syndrome: A Double-Blind, Placebo-Controlled Trial. The Journal of Clinical Endocrinology and Metabolism. June 2023, 108 (7): 1676–1685. PMC 10271219 . PMID 36639249. doi:10.1210/clinem/dgad014.
- ^ Clinical trial number NCT05532020 for "An Open-Label Study of Diazoxide Choline in Patients With Genetic Obesities" at ClinicalTrials.gov