氟哌啶醇
临床资料 | |
---|---|
读音 | /ˌhæloʊˈpɛrɪdɒl/ |
商品名 | Haldol及其他 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682180 |
核准状况 | |
怀孕分级 | |
给药途径 | 口服给药, 肌肉注射, 静脉注射, 储库注射 (如癸酸酯制剂,能够缓慢释放药物(长效制剂),而能减少用药频率。) |
药物类别 | 典型抗精神病药物 |
ATC码 | |
法律规范状态 | |
法律规范 |
|
药物动力学数据 | |
生物利用度 | 60–70% (口服)[2] |
血浆蛋白结合率 | ~90%[2] |
药物代谢 | 肝脏介导[2] |
代谢产物 | • HPP+[3][4][5] |
生物半衰期 | 14–26小时 (静脉注射), 20.7小时 (肌肉注射), 14–37小时 (口服)[2] |
排泄途径 | 胆管 (而进入粪便) 及尿液[2][6] |
识别信息 | |
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CAS号 | 52-86-8 |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.000.142 |
化学信息 | |
化学式 | C21H23ClFNO2 |
摩尔质量 | 375.87 g·mol−1 |
3D模型(JSmol) | |
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氟哌啶醇(INN:haloperidol)以好度(Haldol)等商品名称于市场上贩售,是一种典型抗精神病药物(又称第一代抗精神药物)。[8]用于治疗思觉失调症、妥瑞氏症的抽动症状、双向障碍的躁狂、谵妄、激动、急性精神病和酒精戒断症候群引起的幻觉。[8][9][10]给药方式有口服,肌肉注射或是静脉注射。[8]用药后通常在30至60分钟内发生作用。[8]有每隔4周注射一次的长效药剂(癸酸酯制剂),供患有思觉失调症或相关疾病的人使用,这类人会忘记或拒绝以口服方式用药。[8]
使用氟哌啶醇可能会导致一种称为迟发性运动不能的疾患,且可能是永久性。[8]使用后可能发生神经阻滞剂恶性综合征和心电图中QT间期延长,后者尤其会在静脉注射后发生。[8]此药物在患有失智症的老人中会导致死亡风险升高。[8]个体于怀孕期间服用可能会导致胎儿出现问题。[8][11]罹患帕金森氏症的个体不应使用。[8]
氟哌啶醇于1958年由比利时药学家保罗·杨森领导的团队发现,[12]是从哌替啶(镇痛药)衍生而来的一种药物。[13]它已列入世界卫生组织基本药物标准清单之中,[14]氟哌啶醇是最常使用的典型抗精神病药物,[15]是美国于2020年排名第303的最常使用处方药,开立的处方笺数量超过100万份。[16]
医疗用途
[编辑]氟哌啶醇用于控制下列症状:
- 急性精神病,例如由氯胺酮和苯环己哌啶引起的药物诱发性精神病。[17][18]
- 酒精和阿片类药物戒断的辅助治疗
- 与大脑硬化相关的激动和混乱
- 酒精诱发的精神病
- 酒精戒断症候群所致的幻觉[9]
- 过动性谵妄
- 过动/攻击行为
- 儿童和青少年难以控制的严重行为障碍
- 思觉失调症[19]
- 人格障碍的治疗试验
- 难治性打嗝的治疗[20][21]
- 神经系统疾患的治疗
- 手术后和缓和疗护中的严重恶心和呕吐的治疗
- 作为急性精神科护理中的药物辅助控制[22]
氟哌啶醇虽然曾是精神科急症治疗的主力药物,[22][23]但根据2001年至2005年间发表的多项共识评审,非典型药物在近年来已逐渐取代其地位,成为许多临床治疗的优先选择。[24][25][26]
一项于2013年所做的研究,比较15种抗精神病药物于治疗思觉失调症的疗效,显示氟哌啶醇表现出标准的治疗效果。氟哌啶醇的有效性比齐拉西酮、氯丙嗪和阿塞纳平高出13-16%,与喹硫平、阿立哌唑的效果相当,但比帕利哌酮略差10%。[27]
氟哌啶醇与与某些抗精神病药物(如利培酮)不同,对于血清素迷幻药物(如赛洛西宾(又称裸盖菇素)和麦角酸二乙酰胺(LSD))并无作为解药或是"幻觉终结者"的作用。[28][29][30]
怀孕与母乳哺育期间使用
[编辑]有孕妇使用后可能导致胎儿损害的报告,但此类妇女大多数在怀孕期间接触过多种药物,且目前尚无人类使用的对照研究。根据公认的一般原则,只有在对母亲的益处明显大于对胎儿的潜在风险时,才可在怀孕期间使用此药物。[19]
氟哌啶醇会分泌到母乳中。有几项研究关于此对母乳哺育婴儿的影响,尚未发现对其生长发育有不良影响。[31]
其他应注意处
[编辑]为维持疾病缓解而长期使用氟哌啶醇治疗慢性精神疾病的患者,应将每日剂量逐步降低至最低有效剂量。在某些情况下,可能会在最终停药。[32]建议在长期使用期间进行常规监测,包括测量身体质量指数、血压、空腹血糖和血脂,以降低副作用导致的风险。[33]
氟哌啶醇的外用药物制剂不应被用于治疗恶心,因为研究表明这种疗法并没有比其他方法更为有效。[34]
不良反应
[编辑]根据一项于2013年对15种抗精神病药物进行比较疗效和耐受性的统合分析,氟哌啶醇是最易引起锥体外症候群副作用的药物之一。[27]
使用超过6个月后,有14%的使用者会增加体重。[35]氟哌啶醇可能具有神经毒性。[36]
如果长期服用这种药物,可能会产生心理上的依赖。[37]
禁忌症
[编辑]药物交互作用
[编辑]氟哌啶醇会与下列药物发生各式交互作用:
潜在神经毒性
[编辑]停药
[编辑]英国国家处方集建议在停用抗精神病药物时采逐步减量方式,以避免急性戒断症候群或快速复发。[41]戒断症状通常有恶心、呕吐和食欲减退。[42]其他症状有焦躁不安、出汗增加和睡眠困难。[42]
药物过量
[编辑]处理
[编辑]主要是对症治疗,包括加强监测生命体征,特别是针对QT间期延长,并对严重心律不整采取抗心律不整措施。[19]
预后
[编辑]氟哌啶醇过量有高致死率风险,[43]但个体经积极治疗后的存活率可望提高。
药理学
[编辑]氟哌啶醇是一种常见的精神科用药,属于丁酰苯类抗精神病药。它能有效阻断大脑中的多巴胺D2受体,并长时间停留在受体上,达到治疗的效果。[44]它的作用机制与另一类药物啡噻嗪相似。[21]
药物动力学
[编辑]口服
[编辑]氟哌啶醇的口服剂生物利用度介于60%至70%之间。然而,不同研究报告的平均Tmax(达到峰值浓度时间)和T1/2(生物半衰期)差异很大,分别从1.7至6.1小时和14.5至36.7小时不等。[2]
肌内注射
[编辑]药物经肌内注射后可被快速且完全吸收,具有高生物利用度。健康个体的Tmax(为20分钟,思觉失调症患者为33.8分钟。平均T1/2为20.7小时。[2]长效的氟哌啶醇奎酸酯注射剂仅供肌内注射用,不可进行静脉注射。此针剂于注射后约6天可达血浆峰值浓度,随后浓度下降,生物半衰期约为3周。[46]
静脉注射
[编辑]静脉注射剂的生物利用度为100%,且极快发生作用(仅需数秒)。T1/22为14.1至26.2小时。表观分布容积为9.5至21.7升/公斤。[2]作用持续时间为4至6小时。
化学
[编辑]氟哌啶醇是一种晶体物质,熔点为150°C。[47]晶体在水中的溶解度非常低(1.4毫克/100毫升100),但可溶于氯仿、苯、甲醇和丙酮。它也可溶于0.1摩尔盐酸(3毫克/毫升),但需加热。[48]
历史
[编辑]氟哌啶醇由保罗·杨森领带的团队发现,[49]于1958年在保罗·杨森所创的杨森制药开发,并于同年较晚时在比利时进行首次临床试验。[50][51]
此药物于1967年4月12日获得美国食品药物管理局(FDA)批准,后来由McNeil Laboratories以Haldol(静脉注射剂)品牌名称在美国和其他国家销售。[50]
社会与文化
[编辑]成本
[编辑]氟哌啶醇的价格优势极为突出,较新型抗精神病药物便宜近一百倍,使其成为经济相对弱势患者的更佳选择。[52][53]
名称
[编辑]Haloperidol 是国际非专有药名(INN)、英国批准名称 (BAN)、美国采用名称(USAN)和澳大利亚批准名称(AAN)所认可的名称。
Haloperidol 在全球各地以不同的商品名销售,包括 Aloperidin、Bioperidolo、Brotopon、Dozic、Duraperidol (德国)、Einalon S、Eukystol、Haldol、Halosten、Keselan、Linton、Peluces、Serenace、Serenase及Sigaperidol。[54]
研究
[编辑]氟哌啶醇曾被研究用于治疗忧郁症,[55][56]其机制为: 透过短暂阻断多巴胺受体,大脑会产生一种补偿性反应,增加多巴胺受体的数量,提高对多巴胺的敏感性。当停药后,这种增强的敏感性有助于改善忧郁症状。[55][57][56]
兽医用途
[编辑]氟哌啶醇不仅限于人类医疗,在动物管理,尤其是兽医诊疗和圈养动物管理中,常被用于达到镇静和降低行为激动的效果。[58]
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