國(guó)際獸醫(yī)癲癇工作組共識(shí)建議：歐洲犬癲癇的藥物治療

Sofie F.M. Bhatti1*, Luisa De Risio2 , Karen Mu?ana3 , Jacques Penderis4 , Veronika M. Stein5 , Andrea Tipold5 , Mette Berendt6 , Robyn G. Farquhar7 , Andrea Fischer8 , Sam Long9 , Wolfgang L?scher10, Paul J.J. Mandigers11, Kaspar Matiasek12, Akos Pakozdy13, Edward E. Patterson14, Simon Platt15, Michael Podell16, Heidrun Potschka17, Clare Rusbridge18,19 and Holger A. Volk20?

翻譯 By @蘇蘇蘇蘇喬

校正 By @寵物神經(jīng)科醫(yī)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，一項(xiàng)研究在10例犬身上評(píng)估了托吡酯作為苯巴比妥、溴化鉀和左乙拉西坦的輔助藥物的療效[57]。劑量根據(jù)動(dòng)物調(diào)整（2 ~ 10mg /kg），每日2~3次。鎮(zhèn)靜、共濟(jì)失調(diào)和體重減輕是犬最常見(jiàn)的不良反應(yīng)(表2)。Charalambous等人（2014）[17]的研究表明，該研究總體上存在中/高的偏倚風(fēng)險(xiǎn)。因此，目前沒(méi)有足夠的證據(jù)推薦使用托吡酯作為輔助性抗癲癇藥物[17]。在人類中，托吡酯既可以單獨(dú)使用治療，也可作為輔助療法治療局灶性和全身性抽搐發(fā)作[29,71]。它是一種氨基磺酸替代單糖（sulphamate-substituted monosaccharide），作用于多種信號(hào)機(jī)制，增強(qiáng)GABA能活性，抑制電壓敏感的鈉離子和鈣離子通道（voltagesensitive sodium and calcium channels）、海人藻酸誘發(fā)電流（kainate-evoked currents）和碳酸酐酶同工酶（carbonic anhydrase isoenzymes）[118,139]。從現(xiàn)有的人類數(shù)據(jù)來(lái)看，托吡酯一旦被吸收就不會(huì)被廣泛代謝，70-80%的給藥劑量會(huì)在尿液中排出，同時(shí)排出的藥物形式不會(huì)改變[65]。托吡酯的清除半衰期為2?4小時(shí)。腎功能損害病患的托吡酯清除率降低，因此需要調(diào)整劑量[37]。在犬，托吡酯不能被廣泛代謝，主要通過(guò)尿液排出。然而，犬在服用托吡酯后可出現(xiàn)膽道排泄（biliary excretion）[15]。該藥物與其他藥物發(fā)生臨床相關(guān)相互作用的可能性相對(duì)較低[8,53]。在人類中最常見(jiàn)的不良反應(yīng)是嗜睡、頭暈、共濟(jì)失調(diào)、眩暈和語(yǔ)言障礙[110]。健康的比格犬每天口服劑量為10-150 mg/kg，持續(xù)15天，無(wú)不良反應(yīng)報(bào)告[116]。