Structures already discussed alongside status epilepticus in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
RCSB Protein Data Bank · entry 7W9K · 2.2 Å · ligand O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine (P5S). Experimental structure, not a prediction.
The 2011 review describes a three-stage treatment pathway for tonic-clonic status epilepticus. In early status, buccal midazolam is noted as an important out-of-hospital option. For established status, valproate, levetiracetam and lacosamide are listed as modern choices. For refractory status, a variety of anaesthetics and non-pharmacological therapies are used. The review explicitly states that for stage 2 and stage 3, therapies have almost invariably been assessed only in open studies, and calls for multicentre randomised controlled comparisons. A 2016 review reports that prolonged generalised convulsive seizures may lead to neuronal injury, pharmacoresistance and poor prognosis, and that an updated treatment algorithm emphasises more rapid escalation to third-line therapy for refractory convulsive status epilepticus.
The 2017 overview states that status epilepticus is an emergency associated with neuronal damage, systemic complications, and substantial morbidity and mortality depending on status type, duration, age and aetiology. It notes that morbidity and mortality rates have improved in the past few years, probably due to aggressive use of anti-epileptic drugs in emergency situations. The 2018 proceedings of the 6th London-Innsbruck Colloquium report that over the previous 10 years, 5691 publications on status epilepticus appeared in PubMed, more than in all previous years on the index. The proceedings list new drugs for super-refractory status epilepticus including ketamine, lacosamide, brivaracetam, and the neurosteroids ganaxolone and allopregnanolone. They also state that the most important public health advance in the whole of epilepsy has been the use of benzodiazepine therapies out of hospital using different routes of administration. For the first time, randomised controlled trials have been conducted in the field of established status.
Despite these advances, the evidence base for stage 2 and stage 3 therapies remains weak, consisting almost entirely of open studies. The 2018 proceedings note that the entity of super-refractory status epilepticus has been defined and has attracted wide use, but the optimal weaning of anaesthetics and the long-term consequences of intensive care unit care in children and adults are still under study. What is missing are large, multicentre randomised controlled trials that compare the newer drugs against each other and against standard therapy, particularly for established and refractory status. Better patient stratification by aetiology, EEG pattern and genetic cause is also lacking, as is funding for the kind of comparative effectiveness research that could settle which drug, at which stage, actually improves survival and functional outcome.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 2011 · 57 citations
The treatment of status epilepticus
AbstractPURPOSE OF REVIEW: This review discusses the advances in the treatment of status epilepticus since the first London-Innsbruck Colloquium on Status Epilepticus, held in London in April 2007. RECENT FINDINGS: The review focuses on new drug treatment. The treatment of tonic-clonic status epilepticus is usually divided into three stages. In the first stage (stage of early status epilepticus), buccal midazolam has become an important out-of-hospital treatment option. In the second stage (stage of established status epilepticus) modern treatment choices include valproate, levetiracetam and lacosamide. In the third stage (stage of refractory status epilepticus), a variety of anaesthetics and nonpharmacological therapies can be administered. Treatment should also be focused on the causes of status epilepticus, and immunological therapy is sometimes given in cryptogenic refractory status epilepticus. SUMMARY: There have been a number of advances in recent years in the treatment of status epilepticus. In stage 2 and stage 3 of status epilepticus, the therapies have almost invariably been assessed in open studies only, and there is a need for multicentre randomized controlled therapy comparisons.
https://doi.org/10.1097/wco.0b013e3283446f31Current Drug Metabolism · 2017 · 6 citations
Status Epilepticus: An Overview
AbstractStatus epilepticus (SE) is an emergency situation, where immediate and effective treatment is required in least possible time as it is associated with neuronal damage, systemic complications, substantial morbidity and mortality depending on status type, duration, age and etiology. In the past few years, morbidity and mortality rate were improved, probably may be due to aggressive use of anti-epileptic drugs in emergency situations. Present literature gives an overview of the conditions leading to SE and its management guidelines in hospital and out of hospital setting emphasizing on the available drug therapies. Keywords: Anti-epileptic drugs, delivery systems, management protocols, drug therapy, status epilepticus, drug interactions.
https://doi.org/10.2174/1389200218666170106091705Epilepsia · 2018 · 5 citations · open access
A decade of progress in status epilepticus 2007‐2017: Proceedings of the 6th London‐Innsbruck Colloquium on Status Epilepticus and Acute Seizures
AbstractThis Colloquium was the 6th in a series of biannual conferences, alternating between venues in Britain and Austria, held over the last 10 years. The proceedings of each have been published1-5 as a guide to what was discussed and the main conclusions drawn. Over the past 10 years, much has developed in the area of status epilepticus; we hazard to say that this is one of the fastest growing areas in the whole of epilepsy. This is reflected in the 5691 publications listed in PubMed over the previous 10 years, more than has been published in all the previous years on the PubMed index. During this time, a number of new advances have been made, which were presented and discussed at the previous 5 Colloquia, and in Table 1 we have listed what we consider some of the most significant of these. The basic science understanding of the mechanisms and also the consequences of status epilepticus (SE) has advanced considerably, with advances in receptor trafficking, cerebral inhibition at a cellular and systems level, synaptic function, molecular genetics, epigenetics, and experimental pharmacology. This progress in understanding of the mechanisms responsible for the failure for seizure suppression and seizure perpetuation led to new concepts in the definition of status and the development of new drugs for different stages of SE. In the field of epidemiology, there have been good estimates of the frequency of refractory and super-refractory SE (SRSE). The aging population will lead to an increase in the incidence of SE. A range of new measures to predict outcome and measures of severity have been validated and used across different countries. Studies have been undertaken of the range of uncommon causes of SE, including genetic causes, and both clinical and pathologic studies of autoimmune and mitochondrial causes. The entity of SRSE has been defined and the concept has attracted wide use. The electroencephalography (EEG) patterns of nonconvulsive SE (NCSE) have been better understood and the Salzburg Criteria for defining NCSE have been widely accepted. The advances in the use of benzodiazepine therapies “out of hospital” using different routes of administration have been perhaps the most important public health advances in the whole of epilepsy. There have also been, for the first time randomized controlled trials (RCTs) in the field of established status. New treatment protocols, new drugs, and new types of treatment especially in SRSE, include ketamine, lacosamide, brivaracetam, and neurosteroids, such as ganaxolone and allopregnanolone. Better appreciation of the risks and the benefits of anesthesia led to the development of appropriate treatment protocols. The 6th Colloquium had 7 main themes: The nature of status epilepticus—experimental aspects; the nature of status epilepticus—clinical aspects; status epilepticus in the intensive care unit; the weaning of anesthetics; some regulatory aspects of status epilepticus; audit and registries; and future perspectives—novel therapy and innovation. In addition, there was one Satellite Symposium sponsored by SAGE pharmaceuticals entitled Clinical Controversies in the Treatment of Super-Refractory Status Epilepticus (SRSE). The faculty of 39 (Table 2) was drawn from 13 countries: Austria, China, Croatia, Finland, Germany, India, Ireland, Israel, Italy, South Korea, Switzerland, United Kingdom, and the United States. Seventy-eight posters were accepted for viewing at the colloquium. There were 336 delegates from 5 continents (Figure 1). Financial sponsorship in the form of educational grants, without input into the program, was provided by the following sponsors: SAGE, Eisai, UCB, Upsher-Smith, and GW Pharmaceuticals, and an exhibition was held with the additional exhibitors: Austrian Institute of Technology, AD-TECH/DID Medical, Livanova, Epinet study group, Novartis, Electrical Geodesics, Epilog, and Neuromed. The conference was awarded 15 European CME credits by the European Accreditation Council for Continuing Medical Education (EACCME). There were 30 keynote lectures in the Colloquium. These started with a review of recent work in mitochondrial diseases and SE (Rahman), an account of new work on the circuit mechanism in SE (Kapur), new work on receptor trafficking (Kittler), epigenetic changes in SE (Henshall), neurotrophic factors in SE (Simonato), and next-generation sequencing (Lipkin). These were superb talks and show how far the field has advanced in these basic science areas. There were then clinical talks on boundary syndromes (Shorvon) and a fascinating review of SE due to poisons in warfare (Marini). The presentation on neuroimaging of status (Meletti) demonstrated new imaging techniques for the diagnosis of SE and the study of its consequences, and the lecture on treatment gap in developing countries (Lee) shows how much remains to be done. There were then a series of talks on the intensive care unit management of SE covering the diagnosis of nonconvulsive SE (Trinka), a new prognostic scale from China (Jiang), a review of anesthetic treatments (Hocker), studies of guidelines for the weaning of anesthetics (Colquhoun), the effects of anaesthetics on the EEG (Cole), the long-term consequences of ITU care in children and a new pediatric SE network (Loddenkemper), and a review of SE in the elderly (Leppik). We then led a debate about regulatory aspects of SE, covering 2 specific topics. The question of whether SE should be considered an entity, distinct from epilepsy, from the regulators point of view, and what evidence was needed to license a drug for SE. This was followed by presentations on the Global Audit of refractory SE (Hocker and Ferlisi) and the SENSE registry (Kellinghaus). On the final day, there was a series of papers on new treatments in SE, and these demonstrated to all how fast the therapy field is moving forward. These included the following: propofol hemisuccinate (Rogawski), valnoctamide and SPD (Bialer), brivaracetam (Trinka), perampanel (Rohracher), neurosteroids (Rossetti), and ketamine (Hofler). The session followed with a lecture on new modes of administration (Cloyd) and reactive oxygen species (Walker), and an update on the ESSET trial (Kapur). There were 3 poster prizes awarded: Gaetano Terrone, Italy, received the award for the best poster in basic and clinical investigations; Alexey Kholin, Russian Federation for pediatric and clinical science; and Alexandra Sinclair, UK, for the best poster in treatment and outcome. The winners are entitled to free admission to the 7th Colloquium 2019. None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
https://doi.org/10.1111/epi.14487Pakistan Journal of Pharmaceutical Sciences · 2022 · 1 citations · open access
Clinical efficacy of clonazepam in the treatment of status epilepticus
AbstractTo explore the clinical efficacy of clonazepam in the treatment of status epilepticus. Totally 60 patients with status epilepticus were identified as research subjects and assigned (1:1) via the randomized double-blind method to receive either diazepam (Valium) comparison group) or clonazepam (observation group). After treatment and follow-up visits, the treatment efficacy, incidence of adverse reactions, quality of life, and recurrence were evaluated and compared between the two groups. The total effective rate of the observation group was 93.33%, which was higher than that of 66.67% in the comparison group (P<0.05). A longer mean duration of drug effect was observed in the observation group than in the comparison group (P<0.05). The observation group outperformed the comparison group in terms of quality of life (P<0.05). The observation group had a lower incidence of adverse reactions than the comparison group (P<0.05). The overall recurrence rate in the comparison group was 23.33%, which was significantly higher than that of 6.67% in the observation group (P<0.05). Clonazepam yields a promising efficacy in the treatment of patients with status epilepticus.
https://doi.org/10.36721/pjps.2022.35.3.sp.891-895.1Therapeutic Drug Monitoring · 2023 · 1 citations
Evaluation for Blood Concentration and Efficacy/Safety of Continuous Administration of Thiamylal in Children
AbstractBACKGROUND: Thiamylal exerts excellent sedative effects. However, it is not routinely used because of its serious adverse effects. This study aimed to clarify the target blood concentration range and infusion rate of thiamylal in children by measuring its blood concentration and evaluating its relationship with efficacy and adverse effects. METHODS: This study was approved by the Ethics Committee of Japanese Red Cross Kumamoto Hospital. The authors included 10 children aged between 1 and 7 years who had received continuous intravenous (IV) infusion of thiamylal for the management of refractory status epilepticus, excluding those who met the exclusion criteria. After a 2 mg/kg bolus injection of thiamylal, continuous IV infusion was initiated at a rate of 2-3 mg/kg/h. Thiamylal concentration in the blood was measured using high-performance liquid chromatography. The State Behavioral Scale and the frequency of bolus injections were used to evaluate efficacy. Blood pressure and heart rate were measured to evaluate adverse effects. Statistical analyses of the time to awakening and the factors affecting it were also conducted. RESULTS: The State Behavioral Scale score during thiamylal administration was -2 or lower in all cases, suggesting that the depth of sedation was sufficient. The frequency of bolus injections decreased in a blood concentration-dependent manner, suggesting that the frequency tended to decrease, especially at thiamylal blood concentrations of 20 mcg/mL or higher. An increase of the infusion rate to 3 mg/kg/h was recommended, because the blood concentration may not reach 20 mcg/mL at an infusion rate of 2 mg/kg/h. There was also a case in which a rapid increase in blood concentration accompanied by a decrease in blood pressure and heart rate was observed when the infusion rate was increased to 4 mg/kg/h. Furthermore, the time to awakening after the end of administration correlated with the highest blood concentration during administration; therefore, delayed awakening was noted when using a high dose of thiamylal. CONCLUSIONS: The target blood concentration of thiamylal in children should be 20-30 mcg/mL, and the infusion rate should be based on 3 mg/kg/h.
https://doi.org/10.1097/ftd.0000000000001153Journal of Pharmaceutical Health Care and Sciences · 2024 · 1 citations · open access
Thiamylal serum concentration for refractory convulsive status epilepticus while associated decreased concentrations of concomitant antiepileptics: a case report
AbstractBACKGROUND: Treating refractory status epilepticus (RSE) remains a challenge. Thiamylal can be used as a second- or third-line treatment; however, its potential to induce cytochrome P450 (CYP) activity may reduce the concentration of antiepileptic drugs (AEDs) administered prior to thiamylal. This report details a case of RSE patient treated with thiamylal, with monitored concentrations of thiamylal and other AEDs. CASE PRESENTATION: A 72-year-old healthy man developed RSE. Despite the administration of various AEDs, his seizures were not resolved. Thiamylal was then administered at an initial bolus dose of 2.1 mg/kg, followed by a continuous infusion of 4.2-5.2 mg/kg/h. The initial thiamylal concentration was observed at 7.8 μg/mL, increasing to 35.2 μg/mL before decreasing after dose reduction and cessation. Concurrently, the concentration of concomitant carbamazepine decreased from 5.59 μg/mL to 2.1 μg/mL and recovered as thiamylal concentration decreased. Lesser impacts were noted for other AEDs. CONCLUSIONS: This case report underscored the efficacy of thiamylal in treating RSE. However, it also highlighted the need for clinicians to closely monitor the concentrations of concurrent AEDs, especially carbamazepine, during thiamylal therapy.
https://doi.org/10.1186/s40780-024-00362-wJournal of Neurocritical Care · 2016 · 0 citations · open access
Treatment of Status Epilepticus
AbstractStatus epilepticus is a severe neurological disease associated with substantial mortality and health-care cost. Treatment of status epilepticus should proceed without delay even in the pre-hospital setting because prolonged generalized convulsive seizures may lead to neuronal injury, pharmacoresistance, and poor prognosis. These concepts have led to the establishment of an updated treatment algorithm emphasizing a more rapid escalation to third-line therapy for refractory convulsive status epilepticus. This article reviews the guidelines and current evidence for the management of status epilepticus.
https://doi.org/10.18700/jnc.2016.9.1.1Oxford University Press eBooks · 2016 · 0 citations
Lorazepam for Generalized Status Epilepticus
AbstractAbstract This chapter provides a summary of a landmark study in epilepsy. What is the best initial drug treatment for generalized status epilepticus? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. Lorazepam was shown to be either equally or more efficacious in the treatment of status epilepticus versus other medications. Given its easier use, the researchers preferred it as the first-line treatment for status epilepticus. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.
https://doi.org/10.1093/med/9780199377527.003.0003Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
