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Medicina 2019Antiepileptic drugs are the first treatment option in patients with epilepsy. Drugs developed after 2000 are known as third generation antiepileptic drugs. These... (Review)
Review
Antiepileptic drugs are the first treatment option in patients with epilepsy. Drugs developed after 2000 are known as third generation antiepileptic drugs. These medications offer new mechanisms of action and favorable pharmacokinetics, decreasing the occurrence of side effects and drug-drug interactions. Broad spectrum antiepileptic drugs, such as brivaracetam and clobazam are good choices for generalized tonic colonic seizures and are well tolerated.New sodium channel blockers such as lacosamide and eslicarbazepine, have a more "benign" side effect profile than the first or second generation of sodium channel blockers. These new drugs are useful therapies in patients with epilepsy of difficult control. Cannabidiol and fenfluramine are useful in the treatment of Dravet or Lennox Gastaut syndrome. Allopregnenolona and ganaxolone showed good efficacy in status epilepticus and could play an important future role in this clinical scenario.
Topics: Anticonvulsants; Drug Interactions; Epilepsy; Humans; Status Epilepticus
PubMed: 31603844
DOI: No ID Found -
The Cochrane Database of Systematic... Nov 2010Eclampsia, the occurrence of a seizure (fit) in association with pre-eclampsia, is rare but potentially life-threatening. Magnesium sulphate is the drug of choice for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Eclampsia, the occurrence of a seizure (fit) in association with pre-eclampsia, is rare but potentially life-threatening. Magnesium sulphate is the drug of choice for treating eclampsia. This review assesses its use for preventing eclampsia.
OBJECTIVES
To assess the effects of magnesium sulphate, and other anticonvulsants, for prevention of eclampsia.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (4 June 2010), and the Cochrane Central Register of Controlled Trials Register (The Cochrane Library 2010, Issue 3).
SELECTION CRITERIA
Randomised trials comparing anticonvulsants with placebo or no anticonvulsant, or comparisons of different drugs, for pre-eclampsia.
DATA COLLECTION AND ANALYSIS
Two authors assessed trial quality and extracted data independently.
MAIN RESULTS
We included 15 trials. Six (11,444 women) compared magnesium sulphate with placebo or no anticonvulsant: magnesium sulphate more than a halved the risk of eclampsia (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.29 to 0.58; number needed to treat for an additional beneficial outcome (NNTB) 100, 95% CI 50 to 100), with a non-significant reduction in maternal death (RR 0.54, 95% CI 0.26 to 1.10) but no clear difference in serious maternal morbidity (RR 1.08, 95% CI 0.89 to 1.32). It reduced the risk of placental abruption (RR 0.64, 95% CI 0.50 to 0.83; NNTB 100, 95% CI 50 to 1000), and increased caesarean section (RR 1.05, 95% CI 1.01 to 1.10). There was no clear difference in stillbirth or neonatal death (RR 1.04, 95% CI 0.93 to 1.15). Side effects, primarily flushing, were more common with magnesium sulphate (24% versus 5%; RR 5.26, 95% CI 4.59 to 6.03; number need to treat for an additional harmful outcome (NNTH) 6, 95% CI 5 to 6).Follow-up was reported by one trial comparing magnesium sulphate with placebo: for 3375 women there was no clear difference in death (RR 1.79, 95% CI 0.71 to 4.53) or morbidity potentially related to pre-eclampsia (RR 0.84, 95% CI 0.55 to 1.26) (median follow-up 26 months); for 3283 children exposed in utero there was no clear difference in death (RR 1.02, 95% CI 0.57 to 1.84) or neurosensory disability (RR 0.77, 95% CI 0.38 to 1.58) at age 18 months.Magnesium sulphate reduced eclampsia compared to phenytoin (three trials, 2291 women; RR 0.08, 95% CI 0.01 to 0.60) and nimodipine (one trial, 1650 women; RR 0.33, 95% CI 0.14 to 0.77).
AUTHORS' CONCLUSIONS
Magnesium sulphate more than halves the risk of eclampsia, and probably reduces maternal death. There is no clear effect on outcome after discharge from hospital. A quarter of women report side effects with magnesium sulphate.
Topics: Anticonvulsants; Eclampsia; Female; Humans; Magnesium Sulfate; Pre-Eclampsia; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 21069663
DOI: 10.1002/14651858.CD000025.pub2 -
Revista Brasileira de Anestesiologia 2011Epilepsy is one of the most frequent chronic neurological diseases. Although anesthesia for epilepsy patients is more common in neurosurgery, this group of patients... (Review)
Review
BACKGROUND AND OBJECTIVES
Epilepsy is one of the most frequent chronic neurological diseases. Although anesthesia for epilepsy patients is more common in neurosurgery, this group of patients needs, just as the general population, anesthesia for different diagnostic and therapeutic procedures. This article aims to address the issues of greatest interest to the anesthesiologist in the perioperative management of epileptic patients undergoing anesthesia for non-neurosurgical procedures.
CONTENT
We discuss relevant aspects of pathophysiology, classification and diagnosis of epilepsy; anticonvulsant therapy and interactions with anesthetic drugs; surgery and the ketogenic diet; pro-and anticonvulsant effects of drugs used in anesthesia; preoperative evaluation, intra- and postoperative conduct in epileptic patients, as well as the diagnosis and treatment of perioperative seizures.
CONCLUSIONS
In the perioperative management of epileptic patients is important for anesthesiologists to identify the type of epilepsy, the frequency, severity and the factors triggering the epileptogenic crises; the use of anticonvulsant drugs and possible interactions with drugs used in anesthesia; the presence of ketogenic diet and stimulatory of the vagus nerve, and its implications in anesthetic techniques. It is essential the understanding of pro- and anticonvulsant properties of drugs used in anesthesia, minimizing the risk of seizure activity in the intra- and postoperative. Finally, it is important to outline the diagnosis and initiate treatment of seizures, perioperative, which offers lower both morbidity and mortality.
Topics: Anesthesia; Anticonvulsants; Epilepsy; Humans
PubMed: 21474031
DOI: 10.1016/S0034-7094(11)70028-9 -
Neurotherapeutics : the Journal of the... Oct 2015Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in... (Review)
Review
Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabis-based antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro- and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.
Topics: Animals; Anticonvulsants; Cannabinoids; Epilepsy; Humans
PubMed: 26282273
DOI: 10.1007/s13311-015-0375-5 -
Molecules (Basel, Switzerland) Mar 2021The new series of 3-(2-chlorophenyl)- and 3-(3-chlorophenyl)-pyrrolidine-2,5-dione-acetamide derivatives as potential anticonvulsant and analgesic agents was...
The new series of 3-(2-chlorophenyl)- and 3-(3-chlorophenyl)-pyrrolidine-2,5-dione-acetamide derivatives as potential anticonvulsant and analgesic agents was synthesized. The compounds obtained were evaluated in the following acute models of epilepsy: maximal electroshock (MES), psychomotor (6 Hz, 32 mA), and subcutaneous pentylenetetrazole (PTZ) seizure tests. The most active substance-3-(2-chlorophenyl)-1-{2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethyl}-pyrrolidine-2,5-dione () showed more beneficial ED and protective index values than the reference drug-valproic acid (68.30 mg/kg vs. 252.74 mg/kg in the MES test and 28.20 mg/kg vs. 130.64 mg/kg in the 6 Hz (32 mA) test, respectively). Since anticonvulsant drugs are often effective in neuropathic pain management, the antinociceptive activity for two the promising compounds-namely, and -was also investigated in the formalin model of tonic pain. Additionally, for the aforementioned compounds, the affinity for the voltage-gated sodium and calcium channels, as well as GABA and TRPV1 receptors, was determined. As a result, the most probable molecular mechanism of action for the most active compound relies on interaction with neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Compounds and were also tested for their neurotoxic and hepatotoxic properties and showed no significant cytotoxic effect.
Topics: Analgesics; Animals; Anticonvulsants; Cell Line; Disease Models, Animal; Drug Evaluation, Preclinical; Hep G2 Cells; Humans; In Vitro Techniques; Male; Mice; Molecular Structure; Neuralgia; Pyrrolidines; Seizures; Structure-Activity Relationship
PubMed: 33809109
DOI: 10.3390/molecules26061564 -
Journal of Musculoskeletal & Neuronal... Sep 2021We aimed to investigate fracture risk associated with anticonvulsant use in a population-based sample of men and women.
OBJECTIVES
We aimed to investigate fracture risk associated with anticonvulsant use in a population-based sample of men and women.
METHODS
Data from 1,458 participants (51.8% women) with a radiologically confirmed incident fracture (cases) were compared to 1,796 participants (46.5% women) without fracture (controls). Lifestyle factors, medication use and medical history were self-reported. Associations between anticonvulsant use and fracture were explored using binary logistic regression following adjustment for confounders.
RESULTS
In men, fracture cases and controls differed in age, smoking history, education, alcohol use, and gonadal hormone supplementation. In women, fracture cases and controls differed by previous fracture history, alcohol use, physical activity levels and use of anti-fracture agents. After adjustment for age, pooled anticonvulsant use was associated with a 3.4-fold higher risk of fracture in men and a 1.8-fold higher risk in women. Following further adjustments for confounders these patterns persisted; a 2.8-fold higher fracture risk in men and a 1.8-fold higher fracture risk in women.
CONCLUSIONS
Anticonvulsant use was associated with increased fracture risk, independent of demographic, lifestyle, medical and medication related factors. While further studies exploring potential underlying mechanisms are warranted, regular monitoring of bone health in anticonvulsant users with risk factors may be useful.
Topics: Anticonvulsants; Bone Density; Bone and Bones; Case-Control Studies; Female; Fractures, Bone; Humans; Male; Risk Factors
PubMed: 34465682
DOI: No ID Found -
Current Neuropharmacology 2018Epilepsy is one of the most common neurological disorders worldwide, with about 80 percent of cases thought to be in developing nations where it is mostly linked to... (Review)
Review
BACKGROUND
Epilepsy is one of the most common neurological disorders worldwide, with about 80 percent of cases thought to be in developing nations where it is mostly linked to superstition. The limited supply, high cost as well as low efficacy and adverse side effects of antiepileptic drugs (AEDs) is a matter of major concern. Herbal medicine has always been traditionally part of treatment of epilepsy. Herbal medicines are generally well tolerated, with fewer side effects.
METHOD
To highlight some herbal extracts that have been studied for their anticonvulsant activity in animal models, literature search from PubMed and Science Direct, was performed. The keywords for the search consisted of combinations of the following terms: Herbal antiepileptic and/or anticonvulsant, botanicals + epilepsy. Literature published in the last five years was considered.
RESULTS
Eighteen (18) anticonvulsant herbal agents are reported and discussed. Experiments mostly consisted of phenotypic screens in rodents, with little diversity in screening methods. In most experiments, the tested extracts prolonged the time to onset of seizures and decreased their duration. Most experimenters implicate potentiation of GABAergic activity as the mode of action of the extracts, even though some experimenters did not fully characterise the bioactive chemical composition of their extracts.
CONCLUSION
Potential herbal remedies have shown positive results in animal models. It remains unclear how many make it into clinical trials and eventually making part of the AED list. More rigorous research, applying strict research methodology with uniform herbal combinations, as well as clinical studies are urgently needed.
Topics: Anticonvulsants; Epilepsy; Herbal Medicine; Humans
PubMed: 28521703
DOI: 10.2174/1570159X15666170518151809 -
Molecules (Basel, Switzerland) Nov 2015Epilepsy affects about 1% of the world's population. Due to the fact all antiepileptic drugs (AEDs) have some undesirable side effects and about 30% of epileptic... (Review)
Review
Epilepsy affects about 1% of the world's population. Due to the fact all antiepileptic drugs (AEDs) have some undesirable side effects and about 30% of epileptic patients are not seizure-free with the existing AEDs, there is still an urgent need for the development of more effective and safer AEDs. Based on our research work on antiepileptic compounds and other references in recent years, this review covers the reported work on antiepileptic compounds which are classified according to their structures. This review summarized 244 significant anticonvulsant compounds which are classified by functional groups according to the animal model data, although there are some limitations in the data. This review highlights the properties of new compounds endowed with promising antiepileptic properties, which may be proven to be more effective and selective, and possibly free of unwanted side effects. The reviewed compounds represent an interesting possibility to overcome refractory seizures and to reduce the percentage of patients with a poor response to drug therapy.
Topics: Animals; Anticonvulsants; Drug Discovery; Epilepsy; Humans; Research; Structure-Activity Relationship
PubMed: 26610448
DOI: 10.3390/molecules201119714 -
Journal of Medical Toxicology :... Dec 2017Epilepsy is a neurologic disorder affecting approximately 50 million people worldwide, or about 0.7% of the population [1]. Thus, the use of anticonvulsant drugs in the... (Review)
Review
Epilepsy is a neurologic disorder affecting approximately 50 million people worldwide, or about 0.7% of the population [1]. Thus, the use of anticonvulsant drugs in the treatment of epilepsy is common and widespread. There are three generations of anticonvulsant drugs, categorized by the year in which they were developed and released. The aim of this review is to discuss the pharmacokinetics, drug-drug interactions, and adverse events of the third generation of anticonvulsant drugs. Where available, overdose data will be included. The pharmacokinetic properties of third-generation anticonvulsant drugs include relatively fewer drug-drug interactions, as well as several unique and life-threatening adverse events. Overdose data are limited, so thorough review of adverse events and knowledge of drug mechanism will guide expectant management of future overdose cases. Reporting of these cases as they occur will be necessary to further clarify toxicity of these drugs.
Topics: Anticonvulsants; Drug Interactions; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Risk Factors; Suicide, Attempted
PubMed: 28815428
DOI: 10.1007/s13181-017-0626-4 -
Critical Care (London, England) Jun 2018The incidence of seizures in intensive care units ranges from 3.3% to 34%. It is therefore often necessary to initiate or continue anticonvulsant drugs in this setting.... (Review)
Review
BACKGROUND
The incidence of seizures in intensive care units ranges from 3.3% to 34%. It is therefore often necessary to initiate or continue anticonvulsant drugs in this setting. When a new anticonvulsant is initiated, drug factors, such as onset of action and side effects, and patient factors, such as age, renal, and hepatic function, should be taken into account. It is important to note that the altered physiology of critically ill patients as well as pharmacological and nonpharmacological interventions such as renal replacement therapy, extracorporeal membrane oxygenation, and target temperature management may lead to therapeutic failure or toxicity. This may be even more challenging with the availability of newer antiepileptics where the evidence for their use in critically ill patients is limited.
MAIN BODY
This article reviews the pharmacokinetics and pharmacodynamics of antiepileptics as well as application of these principles when dosing antiepileptics and monitoring serum levels in critically ill patients. The selection of the most appropriate anticonvulsant to treat seizure and status epileptics as well as the prophylactic use of these agents in this setting are also discussed. Drug-drug interactions and the effect of nonpharmacological interventions such as renal replacement therapy, plasma exchange, and extracorporeal membrane oxygenation on anticonvulsant removal are also included.
CONCLUSION
Optimal management of antiepileptic drugs in the intensive care unit is challenging given altered physiology, polypharmacy, and nonpharmacological interventions, and requires a multidisciplinary approach where appropriate and timely assessment, diagnosis, treatment, and monitoring plans are in place.
Topics: Anticonvulsants; Biological Availability; Critical Illness; Half-Life; Humans; Intensive Care Units; Metabolism; Protein Binding
PubMed: 29880020
DOI: 10.1186/s13054-018-2066-1