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Seizure Apr 2017Convulsive status epilepticus (CSE) is a medical emergency associated with high mortality and morbidity. The most recent definition of CSE is a convulsive seizure... (Review)
Review
Convulsive status epilepticus (CSE) is a medical emergency associated with high mortality and morbidity. The most recent definition of CSE is a convulsive seizure lasting more than 5min or consecutive seizures without recovery of consciousness. In adults, for the treatment of the early stages of CSE, diazepam, lorazepam or midazolam are the most common treatments, although the choice of agent seems less important than rapid treatment. Midazolam, when administered intramuscularly (best evidence), buccally, or nasally, is effective and safe in the pre-hospital setting. The antiepileptic drugs, phenytoin, valproate, levetiracetam and, more recently lacosamide, are used in CSE that persists after first-line treatments (established CSE). Phenytoin is more difficult to administer and is less well tolerated. Evidence of the efficacy of lacosamide is scarce. Anaesthetics are the drugs of choice for the treatment of refractory CSE (not responding to second-line drugs). Midazolam seems to be the best tolerated and is the most often used drug, followed by propofol and thiopental (pentobarbital in the USA). A few studies indicate that ketamine is effective with the possible advantage that it can be co-administered with other anaesthetics, such as midazolam or propofol. CSE becomes super-refractory after more than 24h of appropriate treatments and may last weeks. Several anaesthetics have been proposed but evidence is scarce. Autoimmune refractory CSE has been recently identified, and early treatment with immuno-modulatory agents (corticosteroids and IV immunoglobulins and also second-line agents such as cyclophosphamide and rituximab followed by chronic immunosuppressive treatment) is now recommended by many experts.
Topics: Anticonvulsants; Humans; Seizures; Status Epilepticus
PubMed: 28282553
DOI: 10.1016/j.seizure.2017.02.015 -
European Journal of Clinical... Oct 2022Management and dose adjustment are a major concern for clinicians in the absence of specific clinical outcome data for patients on antiepileptic drugs (AEDs), in the... (Review)
Review
Management and dose adjustment are a major concern for clinicians in the absence of specific clinical outcome data for patients on antiepileptic drugs (AEDs), in the event of short-term (5 days) nirmatrelvir/ritonavir co-exposure. Therefore, in this report, we identified drugs that require dose adjustment because of drug-drug interactions (DDIs) between nirmatrelvir/ritonavir and AEDs. We hereby used four databases (Micromedex Drug Interaction, Liverpool Drug Interaction Group for COVID-19 Therapies, Medscape Drug Interaction Checker, and Lexicomp Drug Interactions) and DDI-Predictor.In the light of applying the DDI-Predictor, for carbamazepine, clobazam, oxcarbazepine, eslicarbazepine, phenytoin, phenobarbital, pentobarbital, rufinamide, and valproate as CYP3A4 inducers, we recommend that a dose adjustment of short-term nirmatrelvir/ritonavir as a substrate (victim) drug would be more appropriate instead of these AEDs to avoid impending DDI-related threats in patients with epilepsy.
Topics: Anticonvulsants; Carbamazepine; Clobazam; Cytochrome P-450 CYP3A Inducers; Drug Interactions; Humans; Oxcarbazepine; Pentobarbital; Phenobarbital; Phenytoin; Ritonavir; Valproic Acid; COVID-19 Drug Treatment
PubMed: 35930055
DOI: 10.1007/s00228-022-03370-7 -
Drugs Mar 2018Patients with prolonged seizures that do not respond to intravenous benzodiazepines and a second-line anticonvulsant suffer from refractory status epilepticus and those... (Review)
Review
Patients with prolonged seizures that do not respond to intravenous benzodiazepines and a second-line anticonvulsant suffer from refractory status epilepticus and those with seizures that do not respond to continuous intravenous anesthetic anticonvulsants suffer from super-refractory status epilepticus. Both conditions are associated with significant morbidity and mortality. A strict pharmacological treatment regimen is urgently required, but the level of evidence for the available drugs is very low. Refractory complex focal status epilepticus generally does not require anesthetics, but all intravenous non-anesthetizing anticonvulsants may be used. Most descriptive data are available for levetiracetam, phenytoin and valproate. Refractory generalized convulsive status epilepticus is a life-threatening emergency, and long-term clinical consequences are eminent. Administration of intravenous anesthetics is mandatory, and drugs acting at the inhibitory gamma-aminobutyric acid (GABA) receptor such as midazolam, propofol and thiopental/pentobarbital are recommended without preference for one of those. One in five patients with anesthetic treatment does not respond and has super-refractory status epilepticus. With sustained seizure activity, excitatory N-methyl-d-aspartate (NMDA) receptors are increasingly expressed post-synaptically. Ketamine is an antagonist at this receptor and may prove efficient in some patients at later stages. Neurosteroids such as allopregnanolone increase sensitivity at GABA receptors; a Phase 1/2 trial demonstrated safety and tolerability, but randomized controlled data failed to demonstrate efficacy. Adjunct ketogenic diet may contribute to termination of difficult-to-treat status epilepticus. Randomized controlled trials are needed to increase evidence for treatment of refractory and super-refractory status epilepticus, but there are multiple obstacles for realization. Hitherto, prospective multicenter registries for pharmacological treatment may help to improve our knowledge.
Topics: Adult; Anesthetics, Intravenous; Anticonvulsants; Benzodiazepines; Diet, Ketogenic; GABA-A Receptor Antagonists; Humans; Ketamine; Midazolam; Pentobarbital; Propofol; Status Epilepticus; Thiopental
PubMed: 29368126
DOI: 10.1007/s40265-017-0859-1 -
Journal of the American Veterinary... May 2023Sodium pentobarbital and pentobarbital combination products are commonly used by veterinarians throughout the US for euthanasia of their animal patients. The AVMA... (Review)
Review
A literature review on current practices, knowledge, and viewpoints on pentobarbital euthanasia performed by veterinarians and animal remains disposal in the United States.
Sodium pentobarbital and pentobarbital combination products are commonly used by veterinarians throughout the US for euthanasia of their animal patients. The AVMA Guidelines for the Euthanasia of Animals: 2020 Edition lists barbiturate acid derivatives (pentobarbital) and pentobarbital combination products as an acceptable method of euthanasia for all species when circumstances permit their use. When using pentobarbital products, a veterinarian must consider appropriate handling and disposal of animal remains to avoid the potential for environmental contamination, relay toxicosis in wildlife or domestic animals, and contamination of the animal food supply. Failure to appropriately consider these facets of pentobarbital euthanasia can result in legal and ethical consequences. Despite these concerns, to the authors' knowledge no comprehensive literature review has been published concerning pentobarbital euthanasia or handling and disposal of animal remains following pentobarbital euthanasia. The literature review that follows aims to give a descriptive narrative of the most recent information available on the knowledge, use, challenges, and issues surrounding pentobarbital euthanasia and disposal of animal remains within the US.
Topics: Animals; United States; Humans; Pentobarbital; Veterinarians; Body Remains; Euthanasia, Animal; Animals, Domestic
PubMed: 36800298
DOI: 10.2460/javma.22.08.0373 -
The Veterinary Clinics of North... May 2020The history of companion animal euthanasia includes a blend of good and bad methodology, the shifting landscape of the human-animal bond, and maturation of the... (Review)
Review
The history of companion animal euthanasia includes a blend of good and bad methodology, the shifting landscape of the human-animal bond, and maturation of the veterinary euthanasia experience. Time has shown us that critical exploration of what once was acceptable will lead the way to modern best practices. Animal welfare remains at the heart of the procedure, with equally matched attention now given to client and veterinary team well-being. Although euthanasia will continue to evolve, it is clear through the twenty-first century advancements, a tipping point of necessary change is upon us.
Topics: Animal Welfare; Animals; Animals, Domestic; Euthanasia, Animal; History, 19th Century; History, 20th Century; History, 21st Century; Human-Animal Bond; Terminology as Topic; Veterinary Medicine
PubMed: 32115283
DOI: 10.1016/j.cvsm.2019.12.001 -
Journal of Clinical Medicine Jul 2021Refractory and super-refractory status epilepticus (RSE and SRSE) are life-threatening conditions requiring prompt initiation of appropriate treatment to avoid permanent... (Review)
Review
Refractory and super-refractory status epilepticus (RSE and SRSE) are life-threatening conditions requiring prompt initiation of appropriate treatment to avoid permanent neurological damage and reduce morbidity and mortality. RSE is defined as status epilepticus that persists despite administering at least two appropriately dosed parenteral medications, including a benzodiazepine. SRSE is status epilepticus that persists at least 24 h after adding at least one appropriately dosed continuous anesthetic (i.e., midazolam, propofol, pentobarbital, and ketamine). Other therapeutic interventions include immunotherapy, neuromodulation, ketogenic diet, or even surgical intervention in certain cases. Continuous electroencephalogram is an essential monitoring tool for diagnosis and treatment. In this review, we focus on the diagnosis and treatment of RSE and SRSE.
PubMed: 34300194
DOI: 10.3390/jcm10143028 -
Journal of Molecular Neuroscience : MN Mar 2021KLF4 is a zinc-finger transcription factor that plays an essential role in many biological processes, including neuroinflammation, neuron regeneration, cell...
KLF4 is a zinc-finger transcription factor that plays an essential role in many biological processes, including neuroinflammation, neuron regeneration, cell proliferation, and apoptosis. Through effects on these processes, KLF4 has likely roles in Alzheimer's disease, Parkinson's disease, and traumatic brain injury. However, little is known about the role of KLF4 in more immediate behavioral processes that similarly depend upon broad changes in brain excitability, such as the sleep process. Here, behavioral approaches, western blot, and immunohistochemical experiments were used to explore the role of KLF4 on sedation and the potential mechanisms of those effects. The results showed that overexpression of KLF4 prolonged loss of righting reflex (LORR) duration in pentobarbital-treated mice and increased c-Fos expression in the lateral hypothalamus (LH) and the ventrolateral preoptic nucleus (VLPO), while it decreased c-Fos expression in the tuberomammillary nucleus (TMN). Moreover, overexpression of KLF4 reduced the expression of p53 in the hypothalamus and increased the expression of STAT3 in the hypothalamus. Therefore, these results suggest that KLF4 exerts sedative effects through the regulation of p53 and STAT3 expression, and it indicates a role of KLF4 ligands in the treatment of sleep disorders.
Topics: Animals; Hypnotics and Sedatives; Hypothalamus; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Male; Mice; Mice, Inbred ICR; Pentobarbital; Proto-Oncogene Proteins c-fos; Reflex; STAT3 Transcription Factor; Tumor Suppressor Protein p53
PubMed: 32789565
DOI: 10.1007/s12031-020-01680-y -
Chinese Journal of Integrative Medicine Nov 2022To evaluate the protective function of Babao Dan (BBD) on 5-flurouracil (5-FU)-induced intestinal mucositis (IM) and uncover the underlying mechanism.
OBJECTIVE
To evaluate the protective function of Babao Dan (BBD) on 5-flurouracil (5-FU)-induced intestinal mucositis (IM) and uncover the underlying mechanism.
METHODS
A total of 18 male mice were randomly divided into 3 groups by a random number table, including control, 5-FU and 5-FU combined BBD groups, 6 mice in each group. A single intraperitoneal injection of 5-FU (150 mg/kg) was performed in 5-FU and 5-FU combined BBD groups on day 0. Mice in 5-FU combined BBD group were gavaged with BBD (250 mg/kg) daily from day 1 to 6. Mice in the control group were gavaged with saline solution for 6 days. The body weight and diarrhea index of mice were recorded daily. On the 7th day, the blood from the heart of mice was collected to analyze the proportional changes of immunological cells, and the mice were subsequently euthanized by mild anesthesia with 2% pentobarbital sodium. Colorectal lengths and villus heights were measured. Intestinal-cellular apoptosis and proliferation were evaluated by Tunel assay and immunohistochemical staining of proliferating cell nuclear antigen, respectively. Immunohistochemistry and Western blot were performed to investigate the expressions of components in Wnt/β-catenin pathway (Wnt3, LRP5, β-catenin, c-Myc, LRG5 and CD44).
RESULTS
BBD obviously alleviated 5-FU-induced body weight loss and diarrhea, and reversed the decrease in the number of white blood cells, including monocyte, granulocyte and lymphocyte, and platelet (P<0.01). The shortening of colon caused by 5-FU was also reversed by BBD (P<0.01). Moreover, BBD inhibited apoptosis and promoted proliferation in jejunum tissues so as to reduce the intestinal mucosal damage and improve the integrity of villus and crypts. Mechanically, the expression levels of Wnt/β -catenin mediators such as Wnt3, LRP5, β-catenin were upregulated by BBD, activating the transcription of c-Myc, LRG5 and CD44 (P<0.01).
CONCLUSIONS
BBD attenuates the adverse effects induced by 5-FU via Wnt/β-catenin pathway, suggesting it may act as a potential agent against chemotherapy-induced intestinal mucositis.
Topics: Animals; Male; Mice; Antineoplastic Agents; beta Catenin; Diarrhea; Fluorouracil; Intestinal Mucosa; Mucositis; Pentobarbital; Proliferating Cell Nuclear Antigen; Saline Solution
PubMed: 33420580
DOI: 10.1007/s11655-021-3282-0 -
Neuroscience Letters Apr 2023Pentobarbital-induced anesthesia is believed to be mediated by enhancement of the inhibitory action of γ-aminobutyric acid (GABA)ergic neurons in the central nervous...
Pentobarbital-induced anesthesia is believed to be mediated by enhancement of the inhibitory action of γ-aminobutyric acid (GABA)ergic neurons in the central nervous system. However, it is unclear whether all components of anesthesia induced by pentobarbital, such as muscle relaxation, unconsciousness, and immobility in response to noxious stimuli, are mediated only through GABAergic neurons. Thus, we examined whether the indirect GABA and glycine receptor agonists gabaculine and sarcosine, respectively, the neuronal nicotinic acetylcholine receptor antagonist mecamylamine, or the N-methyl-d-aspartate receptor channel blocker MK-801 could enhance pentobarbital-induced components of anesthesia. Muscle relaxation, unconsciousness, and immobility were evaluated by grip strength, the righting reflex, and loss of movement in response to nociceptive tail clamping, respectively, in mice. Pentobarbital reduced grip strength, impaired the righting reflex, and induced immobility in a dose-dependent manner. The change in each behavior induced by pentobarbital was roughly consistent with that in electroencephalographic power. A low dose of gabaculine, which significantly increased endogenous GABA levels in the central nervous system but had no effect on behaviors alone, potentiated muscle relaxation, unconsciousness, and immobility induced by low pentobarbital doses. A low dose of MK-801 augmented only the masked muscle-relaxing effects of pentobarbital among these components. Sarcosine enhanced only pentobarbital-induced immobility. Conversely, mecamylamine had no effect on any behavior. These findings suggest that each component of anesthesia induced by pentobarbital is mediated through GABAergic neurons and that pentobarbital-induced muscle relaxation and immobility may partially be associated with N-methyl-d-aspartate receptor antagonism and glycinergic neuron activation, respectively.
Topics: Mice; Animals; Receptors, N-Methyl-D-Aspartate; Pentobarbital; Dizocilpine Maleate; Sarcosine; Mecamylamine; gamma-Aminobutyric Acid; Unconsciousness
PubMed: 36907265
DOI: 10.1016/j.neulet.2023.137175 -
Oncotarget Feb 2017
Topics: Allosteric Site; Anesthetics; Animals; Binding Sites; DNA Mutational Analysis; Etomidate; Humans; Ions; Mutation; Neurotransmitter Agents; Oocytes; Pentobarbital; Propofol; Protein Domains; Protein Isoforms; Receptors, GABA-A; Xenopus
PubMed: 28099926
DOI: 10.18632/oncotarget.14616