抗癫痫新药左乙拉西坦的临床应用和安全性

左乙拉西坦(levetiracetam)为吡拉西坦的类似物,是一种新型抗癫痫药,用于部分性发作、肌阵挛发作及原发性全身性强直-阵挛发作的辅助治疗(加用于其他抗癫痫药)。左乙拉西坦口服吸收迅速而完全,血浆药物浓度达峰时间为1.3h。其生物利用度不受食物影响,与血浆蛋白结合率<10%,消除半衰期约为6～8h。成人治疗第1天的初始剂量为1g/d,分2次服用;之后,每2～4周增加1g/d,直至有效控制癫痫发作,最大剂量为3g/d。左乙拉西坦的常见不良反应为嗜睡、无力、头晕。肾功能损害患者及严重肝损害患者使用左乙拉西坦应谨慎并减低剂量。停用左乙拉西坦时应逐渐减量(每2～4周减少1g/d),突然停用易增加癫痫发作频次。     

左乙拉西坦添加治疗儿童癫60例

目的研究左乙拉西坦添加治疗不同类型儿童癫的临床疗效和安全性。方法60例癫患儿,原抗癫治疗药物不变,添加左乙拉西坦治疗。青少年（12～16岁）,体质量≥50 kg者,起始治疗剂量每次500 mg,bid。根据临床效果及耐受性,每日剂量可增加至每次1 500 mg,bid。剂量调整为每2～4周增加或减少500 mg·次 1,bid;其他年龄段及体质量儿童起始剂量20 mg·kg 1·d 1,分2次服用,以每2周增加10 mg·kg 1·d 1的平均剂量逐渐加量,在4周内增加至维持剂量30～40 mg·kg 1·d 1,分2次服用。从最后一次加量开始连续6个月观察左乙拉西坦对不同发作类型儿童癫的疗效和不良反应。结果左乙拉西坦对各型儿童癫均有较好疗效,各型间疗效差异无统计学意义,总有效率75.00%。左乙拉西坦不良反应发生率在维持剂量治疗期为11.67%,均较轻微。结论左乙拉西坦添加治疗儿童各型癫有较好疗效。     

卡马西平致红斑狼疮样综合征

1例女性患者,14岁时因癫痫口服卡马西平,由初始剂量300 mg/d逐渐增至600 g/d。服药10年后,患者出现腹腔积液和血小板减少。其血小板计数5×109/L。停用卡马西平,改用左乙拉西坦。实验室检查示抗核抗体1∶320,抗双链DNA抗体261 IU/ml。考虑红斑狼疮样综合征和卡马西平有关,给予泼尼松治疗,患者的腹腔积液逐渐消退。停用卡马西平50 d后血小板计数103×109/L,检测抗核抗体和抗双链DNA抗体均为阴性,红斑狼疮样综合征症状未再出现。     

丙戊酸致高氨血症脑病二例并文献复习

目的了解丙戊酸致高氨血症脑病(Valproate-induced hyperammonemic encephalopathy,VHE)的临床特点、发病机制和治疗措施。方法分析2例丙戊酸脑病患者的临床资料并复习文献。结果例1为52岁男性患者,发病初期出现反应迟钝、行为异常,按照非惊厥持续状态治疗后症状加重,发现血氨增高并撤用丙戊酸钠,予降氨治疗,2 d后恢复;例2为22岁女性患者,诊断为青少年肌阵挛,近4年一直服用丙戊酸钠,加用左乙拉西坦后出现共济失调、扑翼样震颤,发现血氨升高,停用左乙拉西坦后恢复正常。结论丙戊酸致高氨血症脑病的临床症状不特异,临床医生对丙戊酸的不良反应及药物相互作用应提高警惕,避免漏诊、误诊。     

左乙拉西坦添加治疗儿童耐药性癫痫部分性发作的临床研究

目的观察左乙拉西坦添加治疗儿童耐药性癫痫的疗效、用药方法、剂量和副作用。方法对50例儿童耐药性癫痫部分性发作进行添加左乙拉西坦治疗,观察其疗效。结果左乙拉西坦治疗儿童耐药性癫痫部分性发作,总有效率达72%,17例患儿发作停止。结论左乙拉西坦治疗儿童难治性癫痫有良好的疗效,患儿对其有较好的耐受性,副作用轻微。     

进行性肌阵挛癫痫患者口服苯妥英钠致非惊厥性癫痫持续状态

1例16岁女性进行性肌阵挛癫痫患者,口服苯妥英钠0.15 g、1次/12 h治疗1周后出现非惊厥性癫痫持续状态,脑电图呈全导持续性棘慢波节律。7周后入我院,立即将苯妥英钠减量至0.05 g,2次/d,2 d后停用,同时给予患者丙戊酸钠0.3 g,1次/8 h;氯硝西泮1 mg,1次/12 h;左乙拉西坦0.25 g,1次/12 h。治疗第3天患者肌阵挛发作消失,治疗第6天脑电图示散在棘慢波、慢波,住院12 d,病情平稳出院。     

左乙拉西坦治疗脑卒中后癫痫的疗效观察

目的 观察左乙拉西坦治疗脑卒中后癫痫的临床疗效及安全性.方法 对50例脑卒中后癫痫患者在原用药基础上加用左乙拉西坦治疗24周,以基础期平均每月发作频率与添加治疗24周平均每月发作频率进行比较,观察左乙拉西坦添加治疗卒中后癫痫的临床疗效和不良反应.结果 左乙拉西坦治疗后总有效率78.0％ （39/50）,完全控制率为44.0％（22/50）;左乙拉西坦治疗期32.0％ （16/50）患者出现不良反应,主要有嗜睡乏力、纳差恶心、头晕、易激惹,无严重不良反应.结论左乙拉西坦治疗脑卒中后癫痫发作有效,不良反应少、耐受性好.     

自身对照左乙拉西坦添加治疗耐药性癫痫部分性发作的疗效及安全性

目的:评价左乙拉西坦作为添加剂治疗成人耐药性癫痫部分性发作的疗效和安全性。方法:本试验为单盲、前瞻性研究,27例耐药性癫痫病人在原用药基础上加用安慰剂16 wk,停用安慰剂,再加用左乙拉西坦治疗16 wk,X~2检验比较左乙拉西坦添加期疗效与安慰剂期疗效的差别,并观察其不良反应。结果:左乙拉西坦治疗有效而安慰剂无效的病例13例(48%),安慰剂治疗有效而左乙拉西坦无效的病例5例(19%),左乙拉西坦治疗有效的病例数明显高于安慰剂治疗有效的病例数(P＜0．05)。左乙拉西坦添加治疗期21例(78%)出现不良反应,安慰剂添加期20例(74%)出现不良反应。左乙拉西坦添加治疗期的不良反应主要有情绪异常、头晕、胃肠不适,部分病人有短暂性轻度血白细胞减少,没有病例因严重不良反应退出。结论:左乙拉西坦治疗成人耐药性癫痫部分性发作有效,且不良反应轻,对耐药性癫痫病人是一种有益的选择。     

小儿牛黄清心散联合左乙拉西坦治疗小儿热性惊厥的临床研究

目的探讨小儿牛黄清心散联合左乙拉西坦片治疗小儿热性惊厥的临床疗效。方法选取2015年10月—2018年6月连云港市第二人民医院收治的126例小儿热性惊厥患者作为研究对象,根据治疗方法的不同,将患者分为对照组和治疗组,每组各63例。对照组口服左乙拉西坦片,初始剂量为15mg/kg,2次/d,第8～12天剂量为10mg/kg,2次/d,第13～15天剂量为5mg/kg,2次/d,第l6天停药。治疗组在对照组治疗的基础上口服小儿牛黄清心散,1岁以内,0.5袋/次,1～3岁,1袋/次,3岁以上,1.5袋/次,2次/d。两组患儿均治疗15d,并随访1年。观察两组的临床疗效,比较两组的临床症状改善情况、脑神经因子水平。结果治疗后,对照组和治疗组的总有效率分别为81.0%、95.2%,两组比较差异有统计学意义(P0.05)。治疗后,治疗组退热时间、止惊时间明显短于对照组,惊厥复发率、癫痫转化率明显低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组血清脑源性神经营养因子(BDNF)、神经元特异性烯醇化酶(NSE)、S-100β蛋白(S-100β)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗后治疗组血清脑神经因子水平水平明显低于对照组,两组比较差异有统计学意义(P0.05)。结论小儿牛黄清心散联合左乙拉西坦片治疗小儿热性惊厥具有较好的临床疗效,可改善临床症状,促进脑功能的恢复,减少复发情况,具有一定的临床推广应用价值。     

左乙拉西坦联合吡仑帕奈治疗儿童良性癫痫的临床研究

目的 探讨左乙拉西坦片联合吡仑帕奈片治疗儿童良性癫痫的临床疗效。方法 选取2020年5月—2021年12月聊城市第二人民医院收治的78例良性癫痫患儿,按随机数字表法将所有患者分为对照组和治疗组,每组各39例。对照组口服吡仑帕奈片,起始剂量根据患儿体质量>30 kg为2 mg/d、20～30 kg为1 mg/d,睡前吞服,每隔2周加量1次,每次加量为1个起始剂量,直至以4 mg/d的剂量维持治疗。治疗组在对照组基础上口服左乙拉西坦片,起始剂量每次10 mg/kg,2次/d,每隔2周加量1次,每次加量为1个起始剂量（如第1次加量后剂量调整为每次20 mg/kg,2次/d）,直至以每次30mg/kg,2次/d的剂量维持治疗。两组疗程均为6个月。观察两组的临床疗效,比较治疗前后两组癫痫发作情况、痫性放电率、事件相关电位P300潜伏期和波幅以及血清高迁移率族蛋白B1(HMGB1)、肿瘤坏死因子（TNF）-α、胶质纤维酸性蛋白（GFAP）、γ-氨基丁酸（GABA）水平。结果 治疗后,治疗组总有效率是94.87%,显著高于对照组的79.49%(P<0.05)。治疗后,两组癫痫发作频率、N...     

孟鲁司特钠片致皮疹

1例51岁女性患者，有过敏史，因支气管哮喘，在吸入布地奈德的同时，口服孟鲁司特钠10mg／d。服药第3天，四肢出现皮疹，伴瘙瘁，立即停服孟鲁司特钠，继续使用布地奈德，给予氯雷他定10mg／d口服。3d后，皮疹减轻，1周后皮疹消退。     

Controlled clinical trial comparing flurbiprofen and phenylbutazone in patients with rheumatoid arthritis.

Preliminary results in 12 patients with rheumatoid arthritis are presented from an on-going double-blind, between patient comparison of flurbiprofen and phenylbutazone. Patients received either 300 mg flurbiprofen daily or 400 mg phenylbutazone daily over a 2-week treatment period. Two patients treated with phenylbutazone developed a rash, and treatment was discontinued in 1 of them after Day 2.     

Phase I,pharmacokinetic study of temsirolimus administered orally to patients with advanced cancer

An oral formulation of temsirolimus (Torisel?), an inhibitor of the mammalian target of rapamycin, was evaluated on an intermittent schedule (once daily for 5 days every 2 weeks) in patients with advanced cancer. The maximum tolerated dose was determined to be 75 mg after dose-limiting toxicities of grade 3 elevated aminotransferases (1 patient) and grade 3 rash (1 patient) occurred with a 100-mg dose. The most common temsirolimus-related adverse events were mucositis, rash/maculopapular rash, and asthenia. Six of 12 patients who received the 75-mg dose required dose reductions due to temsirolimus-related adverse events. Two patients who received 75-mg temsirolimus and did not have dose reductions had minor tumor responses. Relative exposure from contributions of both temsirolimus and sirolimus, the principal metabolite, was 17.9% of the 75-mg dose. Thus, oral temsirolimus, 75 mg administered once daily for 5 days every 2 weeks, was further evaluated in patients with metastatic breast cancer.     

左氧氟沙星、头孢哌酮钠舒巴坦钠与克林霉素相关大疱性表皮松解症

1例62岁女性患者因泌尿系统感染给予左氧氟沙星0．5g,1次／d静脉滴注。当日患者双上肢内侧和背部出现红色皮疹,停药并接受抗过敏治疗。第2天因肺部感染给予头孢哌酮钠舒巴坦钠4．0g,10：／8h静脉滴注,克林霉素0．75g,1次／d静脉滴注。6d后患者1：3腔黏膜出现糜烂,全身多处可见弥漫胜红肿和松弛性水疱,部分表皮剥脱,诊断为大疱性表皮松解症。停用抗菌药物并给予甲泼尼龙80mg,1次／d静脉滴注,3d后皮肤症状减轻。次日因皮肤继发感染给予硫酸阿米卡星0．4g,1次／8h静脉滴注,当天再次出现皮疹。经糖皮质激素联合人免疫球蛋白及支持治疗,皮肤症状逐渐好转。     

甲巯咪唑致关节炎综合征

1例64岁男性患者因甲状腺功能亢进症接受甲巯咪唑（10 mg,2次/d口服）和普萘洛尔（10 mg,3次/d口服）治疗。5 d后患者出现皮疹伴瘙痒,自行服用氯雷他定后症状好转。第25天甲巯咪唑剂量调整为10 mg,3次/d口服;普萘洛尔调整为20 mg,3次/d口服,并行保肝治疗。调整剂量后第9天患者出现间歇性、游走性关节疼痛和关节活动受限,第11天停用甲巯咪唑并给予美洛昔康。停用甲巯咪唑后2周患者关节疼痛明显好转,无关节活动受限。     

Levetiracetam concentration in hair is associated with the time schedule of administration: Study on rats

Measurement of hair drug content may be a reliable biomarker of the history of drug exposure, allowing to assess patient long‐term compliance. Studies on correlations between antiepileptic drugs intake and their hair contents are limited. The aim of the study was to determine the association between the history of levetiracetam administration and its content in rat hair in controlled laboratory conditions. Additionally, the effects of levetiracetam on hair growth rate and body‐weights were examined. Three groups of 12 rats each were exposed to different schedules of levetiracetam administration (10 mg/kg i.p.: every 24, 48 and 72 hours) for 30 days. The control group received daily saline injection. Levetiracetam concentrations in hair were assessed by validated LC‐MS/MS method. The mean hair concentrations were as follows: 300 (±100), 170 (±60) and 130 (±80) ng/mg for rats receiving levetiracetam every 24, 48 and 72 hours, respectively. The levetiracetam accumulation in the hair was correlated with the total number of doses received (r = .699, P < .001). Levetiracetam did not affect the hair growth rate and rat body‐weight. The concentration of levetiracetam measured in rat hair represents a reliable marker. It may reflect the adherence to levetiracetam treatment; however, further studies on human beings are needed.     

卡马西平超敏综合征

1例59岁男性患者因耳鸣服用卡马西平0.1 g,1～2次/d,服药7 d后出现双下肢一过性皮疹。停用卡马西平后皮疹消失,但随后耳鸣症状加重,遂入院,给予卡马西平0.1 g,2次/d口服;甲钴胺1 mg,3次/d口服。入院第2天患者体温39.2℃;第3天面颊部、躯干及双侧膝关节处出现红色斑丘疹。血生化检查示丙氨酸转氨酶359 U/L,天冬氨酸转氨酶137 U/L,γ-谷氨酰转移酶506 U/L,乳酸脱氢酶273 U/L。停用卡马西平及甲钴胺,给予甲泼尼龙及抗过敏治疗。2 d后体温恢复正常,5 d后皮疹、肝功能逐渐好转。入院第9天患者再度发热,体温38.1℃,随后皮疹再次出现,且逐渐增多,遍布全身。实验室检查:白细胞13.78×10~9/L,嗜酸粒细胞0.113;丙氨酸转氨酶187 U/L,天冬氨酸转氨酶45 U/L,γ-谷氨酰转移酶374 U/L,乳酸脱氢酶239 U/L。诊断为卡马西平所致药物超敏综合征,给予甲泼尼龙加用人免疫球蛋白治疗,皮疹症状及肝功能逐渐好转。入院第16天患者双下肢再次出现皮疹,经甲泼尼龙及对症治疗后缓解。     

头孢硫脒联合美洛西林静脉滴注诱发大疱性表皮松解症

1例7岁女童为预防术后感染给予头孢硫脒2.0 g加入0.9%氯化钠溶液100 ml中静脉滴注,1次/d;美洛西林2.0 g加入5%葡萄糖注射液100 ml中静脉滴注,1次/d,共用药9 d。停药第2天,患儿出现全身瘙痒,伴散在皮疹、低热。之后皮疹进行性加重,呈弥散性紫红色,表面可见水疱、部分糜烂,以躯干为主,伴口腔黏膜、眼结膜糜烂及脓性渗出,遂入院。给予阿奇霉素、夫西地酸、甲泼尼龙、人免疫球蛋白及外用药治疗。患儿皮肤症状逐渐好转,2周后痊愈出院。     

Folic acid hypersensitivity and fever: a case report

An apparent case of folic acid hypersensitivity and fever in a 36-year-old anephric man is reported. The patient first experienced pruritus when he received 1 mg of folic acid daily; the drug subsequently was discontinued. Three months later, after administration of 1 mg of folic acid daily, the patient became febrile and pruritic. Fever, generalized pain, chills, urticaria and pruritus persisted despite administration of acetaminophen/oxycodone tablets. Leukocytosis was not present. Challenge with a 10-mg/ml folic acid solution intradermally revealed the patient was hypersensitive to folic acid. Previous reports of folic acid-induced hypersensitivity are reviewed. Hypersensitivity to folic acid should be suspected if a patient experiences fever or rash, or both, while receiving folic acid and if neither symptom can be attributed to infection or other pathologic state.     

卡瑞利珠单抗联合阿帕替尼致严重皮肤不良反应1例★

1例80岁男性患者因左肺腺癌行6周期化疗后进展，采用免疫治疗，给予卡瑞利珠单抗0.2 g静脉滴注（d1，21 d为1个周期）。首次静脉滴注卡瑞利珠单抗后1周，患者躯干部出现多处皮疹伴瘙痒，对症治疗后好转。继续第2周期卡瑞利珠单抗联合阿帕替尼治疗后5 d，患者头面部、躯干及四肢再次出现大面积皮疹伴瘙痒，诊断为发疹型药疹。停用卡瑞利珠单抗及阿帕替尼，给予糖皮质激素和抗过敏药物等治疗，10 d后皮疹基本消退。