Zonisamide in refractory epilepsies of childood and adolescence
JP ErnstAdelheid Wiemer‐KruelKarl StroblC. SchröterDaniel NeumannHoward W. BrucknerBarbara HillenbrandJ. Fahrbach
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Abstract:
Introduction: Zonisamide is admitted in Japan since 17 and in the United States since 6 years. In different studies a favourable effect could be shown in refractory epilepsies. Zonisamide was introduced in Germany in June 2005. The use is limited to adults in the moment.Keywords:
Zonisamide
Refractory (planetary science)
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Seperti pada dewasa, teknik regional anestesi pada pediatrik kini makin popular digunakan oleh ahli anestesikarena keuntungannya. Namun demikian selalu ada risiko dan kemungkinan timbulnya komplikasi dari setiap tindakan yang dilakukan, termasuk tindakan anestesi regional pada pediatrik. Insidensi komplikasi anestesi regional pada pediatrik tidak banyak, dan kalaupun terjadi komplikasi adalah minor. Komplikasi bisa diakibatkan dari identifikasi ruang saraf, alat, obat, teknis tindakan anestesi regionalnya dan komplikasi lainnya.Walaupun tidak banyak kejadian komplikasi regional anestesi yang dilaporkan pada pediatrik, dan bukanlah komplikasi yang fatal, teknik regional anestesi pada pediatrik harus dilakukan dengan lebih hatihati, pertimbangan risiko dan keuntungannya untuk menghindari terjadinya komplikasi, terlebih karena kebanyakan komplikasi dapat dihindari dengan mempelajari teknik yang benar, menggunakan peralatan yang sesuai, dan sangat menerapkan prinsip keamanan pada pasien dengan baik.
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Genentech is partnering with the German cancer company Affimed to develop immunotherapies for multiple kinds of solid and blood cancers. Affimed is developing therapies that engage natural killer cells of the innate immune system to help direct them to attack cancer cells. Genentech will pay Affimed $96 million up front and up to $5 billion more in potential payments.
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過去に2回以上の部分発作を示す, それまで未治療の潜因性局在関連性てんかん患児45例を対象に, zonisamide (ZNS) を単剤で1日1回の投与を行い, 血中濃度の日内変動 (最高/最低血中濃度比) と年齢的変化を検討した。ZNSの初回維持量は8mg/kg/dayを基準としたが, 最高/最低血中濃度比は1.25±0.13で, 日内の血中濃度は比較的一定に保たれた。さらに, 前述の対象のうち, 調査時まで12カ月以上にわたり経過を観察しえた25例について, ZNS単剤1日1回投与法の臨床効果を血中濃度面から検討した。初回維持量で, 25例中5例で発作が再発し, 3例で眠気が出現したが, 再発例は最低血中濃度が15μg/mll前後の者に多く, 眠気は最高血中濃度が40μg/ml以上の者に出現した。また, ZNS単剤治療を継続した22例中8例では, 治療開始後12カ月の時点で, 脳波上のてんかん発射が消失していた。
Zonisamide
partial seizures
Complex partial seizures
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Zonisamide is a modern antiepileptic drug (AED) that is distinguished from other AEDs by its unique structure and broad mechanistic profile. Preclinical studies have reported a range of potential mechanisms of action for zonisamide, such as blocking voltage-gated sodium channels, reduction of T-type calcium channel currents, and enhancement of gamma-aminobutyric acid (GABA)-mediated inhibition, which are indicative of its broad antiseizure effects. Zonisamide has a favorable linear pharmacokinetic profile, a long half-life, and a low incidence of protein-binding interactions with other AEDs. Hepatically metabolized through the cytochrome P450 pathway, zonisamide does not induce its own metabolism or liver enzymes. For more than 2 decades, zonisamide has been extensively used as monotherapy and adjunctive therapy for the treatment of partial and generalized seizures in pediatric and adult patients in Japan. Zonisamide was approved in the USA in 2000 as adjunctive therapy for partial seizures in adults. With over 2 million patient-years of exposure internationally, zonisamide has demonstrated safety and efficacy against a multitude of epilepsy and seizure types, including both partial and generalized seizures. This review focuses on the experience and use of zonisamide in partial seizures, as well as possible new uses for zonisamide.
Zonisamide
partial seizures
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Abstract AIM: To evaluate the efficacy of zonisamide as a monotherapy in dogs with idiopathic epileptic seizure. METHODS: The experiment was conducted on 10 dogs with idiopathic epilepsy that were treated at the Seoul National University Hospital for Animals. A diagnosis was conducted based on physical and neurologic examination, complete blood count and chemical analysis, magnetic resonance imaging and cerebrospinal fluid analyses. Idiopathic epilepsy was diagnosed when all of these examinations were normal. Oral zonisamide was administrated to 10 dogs with idiopathic epilepsy at 5–15 mg/kg per os every 12 h to achieve a concentration of zonisamide in serum of 10–40 μg/mL. The frequency of seizures before and after the administration of zonisamide therapy was recorded and the concentrations of zonisamide in serum were measured. RESULTS: Six (60%) of the dogs were favourable responders to treatment, showing a ≥50% reduction in monthly frequency of seizures. Of the remaining four, two dogs did not show a reduction and the other two showed an increase in frequency of seizures. The mean dosage of zonisamide for favourable responders was 7.92 (SD 3.79) mg/kg, which was administered orally twice a day. Only one dog, which was one of the unfavourable responders in the whole study, experienced mild side effects. CONCLUSIONS: Among the dogs treated with oral zonisamide, 60% responded favourably. The effect of zonisamide as an anticonvulsant drug was demonstrated in this study. CLINICAL RELEVANCE: Based on these results, zonisamide monotherapy is effective in some dogs with idiopathic epilepsy.
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Zonisamide is an antiepileptic drug widely used to treat seizures worldwide. In additrion to epilepsy, zonisamide may have beneficial efficacy in various neurological or psychiatric diseases. This article reviews the structure, mechanism of action, pharmacokinetics and possible antiparkinsonian action of zonisamide. A multicentered, randomized, double-blind, placebo-controlled study conducted in Japan provided data suggesting that zonisamide, as an add-on treatment, has efficacy in treating motor symptoms in patients with Parkinson’s disease (PD). Zonisamide may be effective in reducing the duration of ‘off’ time in patients with PD treated with L-DOPA. The therapeutic doses of zonisamide for the treatment of PD are 50–100 mg/day, considerably lower than those for the treatment of epilepsy (200–400 mg/day). It is expected that zonisamide will be safe and tolerated in patients with PD, as it has been used as an antiepileptic for more than 15 years; however, further studies are required to evaluate its safety and tolerability in the treatment of PD. The pharmacological mechanisms of the beneficial actions of zonisamide in PD remain unclear. Various hypotheses have been proposed, but the supporting data are not yet sufficient to draw any conclusions. Further basic research is required to advance our understanding of the antiparkinsonian mechanism of zonisamide.
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Objective: TO describe a series of serum concentrations of zonisamide in a pregnant woman. Case Summary: A 30-year-old woman with primary generalized tonic–clonic seizures and myoclonic jerks was taking zonisamide 200 mg daily as her sole antiepileptic agent when she conceived. She continued on zonisamide throughout her pregnancy. The zonisamide concentrations ranged between 7.5 μg/mL and 17 μg/mL during pregnancy, with the exception of a 4.4-μg/mL concentration at 27 weeks postconception. Following this lower concentration, the zonisamide dose was increased to 300 mg/day at week 29. She had an uneventful pregnancy, with only occasional myoclonic jerks, and delivered at 41 weeks. At 42 weeks, white taking zonisamide 300 mg/day, her concentration was 20.8 μg/mL Discussion: A single report from Japan reviewed 26 cases of prenatal exposure to zonisamide. Twenty-two offspring were exposed to zonisamide monotherapy; 4 were exposed to polytherapy. During the first trimester, 2 pregnant women on zonisamide and at least one other antiepileptic medication had serum concentrations of 6.1 μg/mL and 6.2 μg/mL; 2 of the Infants had teratogenic effects. Teratogenicity has also been reported in animals. There are no other published data regarding zonisamide concentrations during pregnancy. Conclusions: The change in zonisamide serum concentrations in a pregnant woman suggests an increase in clearance at the end of the second trimester.
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