Phenytoin sodium

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PHT可能不会渗透入母乳中或者渗透进入母乳的量不会引起临床表现 PHT probably cross the placenta in potentially clinically important amounts (one Class I and supporting Class II studies or two or more Class II studies). Harden CL, Pennell PB, Koppel BS, Hovinga CA, Gidal B, Meador KJ, Hopp J, Ting TY, Hauser WA, Thurman D, Kaplan PW, Robinson JN, French JA, Wiebe S, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Shafer PO, Le Guen C; American Academy of Neurology; American Epilepsy Society. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009 Jul 14;73(2):142-9. doi: 10.1212/WNL.0b013e3181a6b325. Epub 2009 Apr 27. PMID: 19398680; PMCID: PMC3475193. 妊娠可能导致PHT清除率增加、血药浓度降低（一项Ⅰ类研究）。 Pregnancy probably causes an increase in the clearance and a decrease in the level of PHT during pregnancy (one Class I study). Harden CL, Pennell PB, Koppel BS, Hovinga CA, Gidal B, Meador KJ, Hopp J, Ting TY, Hauser WA, Thurman D, Kaplan PW, Robinson JN, French JA, Wiebe S, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Shafer PO, Le Guen C; American Academy of Neurology; American Epilepsy Society. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009 Jul 14;73(2):142-9. doi: 10.1212/WNL.0b013e3181a6b325. Epub 2009 Apr 27. PMID: 19398680; PMCID: PMC3475193. 应考虑在妊娠期间监测PHT水平（Level B）。 Monitoring of PHT levels during pregnancy should be considered (Level B). Harden CL, Pennell PB, Koppel BS, Hovinga CA, Gidal B, Meador KJ, Hopp J, Ting TY, Hauser WA, Thurman D, Kaplan PW, Robinson JN, French JA, Wiebe S, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Shafer PO, Le Guen C; American Academy of Neurology; American Epilepsy Society. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009 Jul 14;73(2):142-9. doi: 10.1212/WNL.0b013e3181a6b325. Epub 2009 Apr 27. PMID: 19398680; PMCID: PMC3475193.

抗癫痫药物与肥胖的关系：很多种AEDs，包括丙戊酸、卡马西平、苯妥英钠、加巴喷丁、氨己烯酸等都可能导致体重增加。其中丙戊酸导致的PCOS是青春期癫痫女性肥胖的重要原因。体重增加也常使癫痫患者的依从性下降或中断治疗。因此，选择AEDs需对药效和药物不良反应综合考虑。用药期间还应定期监测患者身高、体重、体质指数、血脂、血糖等指标，以指导癫痫患者体重的控制。 "关于成人癫痫患者长程管理的专家共识." 中华神经科杂志 .07(2013):496-499.

对新生儿应观察是否出现与AEDs相关的副作用，如苯巴比妥可导致新生儿觉醒程度降低和嗜睡，丙戊酸可能与新生儿易激惹相关，拉莫三嗪可能会诱发新生儿皮疹。与透过胎盘屏障的药物浓度相比，丙戊酸、苯巴比妥、苯妥英钠、卡马西平、拉莫三嗪、托吡酯等药物在母体乳汁内的药物浓度较低，对胎儿的影响相对较小，但左乙拉西坦在乳汁内浓度较高，相关风险有待进一步临床研究证实。大部分患者在医生指导下，可进行母乳喂养。在母乳喂养过程中，如出现长时间的镇静、对喂养不感兴趣、体质量不增加等表现，则应立即停止母乳喂养。 中国医师协会神经内科分会癫(癎)专委会. "妊娠期女性抗癫(癎)药物应用中国专家共识." 中国医师杂志 17.7(2015):969-971. 对于分娩期间出现剧烈呕吐无法服药的患者，可暂予注射苯妥英钠替代口服以控制发作。 对于之前已经口服苯妥英钠的患者，可予相同剂量苯妥英钠分次静脉注射；若患者之前服用其他AEDs，可给予苯妥英钠15～20mg/kg负荷剂量静脉注射后，再给予8mg／(kg·d) 的剂量分两次维持(≤25mg／min)，同时需严密监测患者发作情况。 若患者漏服AEDs>12h，应立即就诊，必要时可考虑苯妥英钠注射。 中国医师协会神经内科分会癫(癎)专委会. "妊娠期女性抗癫(癎)药物应用中国专家共识." 中国医师杂志 17.7(2015):969-971. 卡马西平、奥卡西平、苯巴比妥、苯妥英钠、托吡酯等肝微粒体酶诱导的AEDs，可透过胎盘促进胎儿体内维生素K1氧化降解，导致新生儿出血性疾病的风险增加。建议患者在妊娠最后一个月，每日口服20 mg维生素K1，以减少胎儿发生出血性疾病的风险。 中国医师协会神经内科分会癫(癎)专委会. "妊娠期女性抗癫(癎)药物应用中国专家共识." 中国医师杂志 17.7(2015):969-971.

ban she.女性患者尤其关注药物对容貌的影响，长期使用苯妥英可导致皮肤多毛症和齿龈增生，应尽可能避免长期使用。 Li, S. and Hong, Z., 2015. Lin chuang zhen liao zhi nan. Beijing: Ren min wei sheng chu

苯妥英钠

根据EURAP已知的MCM风险，推荐4种AEDs作为局灶性癫痫的替代物：左乙拉西坦、拉莫三嗪、奥卡西平、卡马西平。其中对卡马西平的剂量限制尤为重要。不推荐使用托吡酯、苯妥英和巴比妥酸盐。 Four AEDs can be recommended as alternatives for focal epilepsy based on known risks of MCMs from the EURAP registry. These are levetiracetam, lamotrigine, oxcarbazepine, and carbamazepine. Dose restriction is especially important in carbamazepine. Topiramate, phenytoin, and barbiturates cannot be recommended due to their teratogenic potential. There are insufficient data for the remaining AEDs, but this does not mean they are safe. Toledo M, Mostacci B, Bosak M, Jedrzejzak J, Thomas RH, Salas-Puig J, Biraben A, Schmitz B. Expert opinion: use of valproate in girls and women of childbearing potential with epilepsy: recommendations and alternatives based on a review of the literature and clinical experience-a European perspective. J Neurol. 2020 Apr 1. doi: 10.1007/s00415-020-09809-0. Epub ahead of print. PMID: 32239268.

Phenytoin sodium

An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.

The sodium salt form of phenytoin, a hydantoin derivate and non-sedative antiepileptic agent with anticonvulsant activity. Phenytoin sodium promotes sodium efflux from neurons located in the motor cortex, thereby stabilizing the neuron and inhibiting synaptic transmission. This leads to a reduction in posttetanic potentiation at synapses, an inhibition of repetitive firing of action potentials and ultimately inhibits the spread of seizure activity.

Phenytoin sodium

[GRADES OF RECOMMENDATION:C] Based on limited evidence, in utero exposure to carbamazepine and lamotrigine does not appear to adversely affect neurodevelopment of the offspring. There is very little evidence for levetiracetam and phenytoin. Parents should be informed that evidence on long-term outcomes is based on small numbers of children. 【推荐等级：C】应告知WWE及其伴侣，关于宫内暴露于AEDs产生的长期神经发育结果是基于少数儿童的。有限的证据表示，宫内接触CBZ和LTG似乎不会影响后代神经生长发育；使用LEV和PHT的证据很少。 https://www.rcog.org.uk/guidance/browse-all-guidance/green-top-guidelines/epilepsy-in-pregnancy-green-top-guideline-no-68/

[GRADES OF RECOMMENDATION:C] Women taking enzyme-inducing AEDs (carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate and eslicarbazepine) should be counselled about the risk of failure with some hormonal contraceptives. 【推荐等级：C】应告知服用酶诱导型AEDs（卡马西平、苯妥英、苯巴比妥、扑米酮、奥卡西平、托吡酯、艾司利卡西平）的WWE避孕失败的风险。 https://www.rcog.org.uk/guidance/browse-all-guidance/green-top-guidelines/epilepsy-in-pregnancy-green-top-guideline-no-68/

与GBP、LTGT和PM等新型AEDs相比，传统AEDs（PTH、PB、CBZ、VPA）并不会大量转移到母乳中（Level Ⅱ-Ⅲ）。 First-generation AEDs (PTH, PB, CBZ, and VPA) are not transferred into breast milk in clinically significant amounts, in contrast with GBP, LTG, and TPM16 (LE II-III). Experience with novel AEDs is limited. Mauri Llerda JA, Suller Marti A, de la Peña Mayor P, Martínez Ferri M, Poza Aldea JJ, Gomez Alonso J, Mercadé Cerdá JM. The Spanish Society of Neurology's official clinical practice guidelines for epilepsy. Special considerations in epilepsy: comorbidities, women of childbearing age, and elderly patients. Neurologia. 2015 Oct;30(8):510-7. English, Spanish. doi: 10.1016/j.nrl.2014.08.002. Epub 2015 Jan 21. PMID: 25618222. 妊娠期AEDs水平可能会发生波动，已观察到PHT、CBZ和LTG清除率增加，且存在较大的个体差异，因此专家建议至少每季度监测一次这些AEDs血药浓度（experts recommend monitoring those levels at least quarterly）。条件允许的话，也可以对LEV和OXC的血药浓度（剂量）进行控制。 Plasma levels of AEDs can change during pregnancy. Increased clearance of PHT, CBZ, and LTG with considerable inter-individual variability is observed, so experts recommend monitoring those levels at least quarterly. Controlling plasma levels or adjusting doses of LEV and OXC is also needed when possible. Mauri Llerda JA, Suller Marti A, de la Peña Mayor P, Martínez Ferri M, Poza Aldea JJ, Gomez Alonso J, Mercadé Cerdá JM. The Spanish Society of Neurology's official clinical practice guidelines for epilepsy. Special considerations in epilepsy: comorbidities, women of childbearing age, and elderly patients. Neurologia. 2015 Oct;30(8):510-7. English, Spanish. doi: 10.1016/j.nrl.2014.08.002. Epub 2015 Jan 21. PMID: 25618222.

55-Diphenyl-24-imidazolidinedione Monosodium Salt phenytoin sodium Diphenylhydantoin sodium Diphenylhydantoinate Sodium Phenytoin sodium (substance) Dilantin Sodium Diphenylhydantoinate Dihydan Diphenylhydantoin Hydantol Epanutin Difenin 55-diphenylimidazolidine-24-dione Fenitoin Antisacer 55-Diphenylhydantoin Epamin

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