国际兽医癫痫工作组共识建议：欧洲犬癫痫的药物治疗

Sofie F.M. Bhatti1*, Luisa De Risio2 , Karen Muñana3 , Jacques Penderis4 , Veronika M. Stein5 , Andrea Tipold5 , Mette Berendt6 , Robyn G. Farquhar7 , Andrea Fischer8 , Sam Long9 , Wolfgang Löscher10, Paul J.J. Mandigers11, Kaspar Matiasek12, Akos Pakozdy13, Edward E. Patterson14, Simon Platt15, Michael Podell16, Heidrun Potschka17, Clare Rusbridge18,19 and Holger A. Volk20 

翻译 By @苏苏苏苏乔

校正 By @宠物神经科医生高健 

Topiramate 托吡酯

In 2013, one study evaluated the efficacy of topiramate as an adjunct to PB, KBr, and levetiracetam in 10 dogs [57]. The dose was titrated (2−10 mg/kg) two to three times daily. Sedation, ataxia and weight loss were the most common adverse effects in dogs (Table 2). According to Charalambous et al. (2014) [17], the study demontsrated an overall moderate/high risk of bias. Thus, there is currently insufficient evidence to recommend the use of topiramate as an adjunct AED [17]. In humans, topiramate has served both as a monotherapy and adjunctive therapy to treat focal and generalised seizures [29, 71]. It is a sulphamate-substituted monosaccharide that acts on multiple signalling mechanisms enhancing GABA-ergic activity and inhibiting voltagesensitive sodium and calcium channels, kainate-evoked currents and carbonic anhydrase isoenzymes [118, 139]. From the available human data, topiramate is not metabolized extensively once absorbed, with 70−80 % of an administered dose eliminated unchanged in the urine [65]. Topiramate has an elimination half-life of 2−4h. Clearance of topiramate is reduced in patients with renal impairment, necessitating dosage adjustments [37]. In dogs, topiramate is not extensively metabolized and is primarily eliminated unchanged in the urine. However, biliary excretion is present following topiramate administration in dogs [15]. The drug has a relatively low potential for clinically relevant interactions with other medications [8, 53]. The most commonly observed adverse effects in humans are somnolence, dizziness, ataxia, vertigo and speech disorders [110]. No adverse reactions were reported in healthy Beagle dogs administered 10−150 mg/kg daily oral doses for 15 days [116].

2013年，一项研究在10例犬身上评估了托吡酯作为苯巴比妥、溴化钾和左乙拉西坦的辅助药物的疗效[57]。剂量根据动物调整（2 ~ 10mg /kg），每日2~3次。镇静、共济失调和体重减轻是犬最常见的不良反应(表2)。Charalambous等人（2014）[17]的研究表明，该研究总体上存在中/高的偏倚风险。因此，目前没有足够的证据推荐使用托吡酯作为辅助性抗癫痫药物[17]。在人类中，托吡酯既可以单独使用治疗，也可作为辅助疗法治疗局灶性和全身性抽搐发作[29,71]。它是一种氨基磺酸替代单糖（sulphamate-substituted monosaccharide），作用于多种信号机制，增强GABA能活性，抑制电压敏感的钠离子和钙离子通道（voltagesensitive sodium and calcium channels）、海人藻酸诱发电流（kainate-evoked currents）和碳酸酐酶同工酶（carbonic anhydrase isoenzymes）[118,139]。从现有的人类数据来看，托吡酯一旦被吸收就不会被广泛代谢，70-80%的给药剂量会在尿液中排出，同时排出的药物形式不会改变[65]。托吡酯的清除半衰期为2−4小时。肾功能损害病患的托吡酯清除率降低，因此需要调整剂量[37]。在犬，托吡酯不能被广泛代谢，主要通过尿液排出。然而，犬在服用托吡酯后可出现胆道排泄（biliary excretion）[15]。该药物与其他药物发生临床相关相互作用的可能性相对较低[8,53]。在人类中最常见的不良反应是嗜睡、头晕、共济失调、眩晕和语言障碍[110]。健康的比格犬每天口服剂量为10-150 mg/kg，持续15天，无不良反应报告[116]。