Newer Anti Epileptic Drugs (original) (raw)
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Epilepsy: the next generation drugs (a review)
Journal of Drug Delivery and Therapeutics, 2019
Epilepsy is a disease characterized by spontaneous recurrence of unprovoked seizures. Seizures and epilepsy are different disorders, and the terms should not be used interchangeably. It is not accurate to refer to seizures as epilepsy, although “seizure disorder” refers to epilepsy. Seizures are common and are treated in all branches of medicine. Approximately 10% of the population will have one or more seizures during their lifetime. Seizures are symptoms that occur in acute illness, i.e., provoked seizures, or in epilepsy, ie, unprovoked seizures. Antiepileptic drugs (AEDs) are pharmacologic agents used to reduce the frequency of epileptic seizures. “Antiepileptic” drug is a misnomer, because these drugs are effective as symptomatic treatment of seizures, i.e., the symptoms of epilepsy, not as treatment of epilepsy itself. Recent discoveries in molecular biology and genetics have elucidated a genetic basis for some epilepsy syndromes, which will lead to new treatments. This review...
Antiepileptic drugs: newer targets and new drugs
International Journal of Basic and Clinical Pharmacology, 2016
Epilepsy is a common neurological disorder affecting 0.5-1% of the population in India. Majority of patients respond to currently available antiepileptic drugs (AEDs), but a small percentage of patients have shown poor and inadequate response to AEDs in addition to various side effects and drug interactions while on therapy. Thus there is a need to develop more effective AEDs in drug resistant epilepsy which have a better safety profile with minimal adverse effects. The United States food and drug administration (USFDA) has approved eslicarbazepine acetate, ezogabine, perampanel and brivaracetam which have shown a promising future as better AEDs and drugs like ganaxolone, intranasal diazepam, ICA-105665, valnoctamide, VX-765, naluzotan are in the pipeline.
Recent advances in the management of epilepsy
Northern International Medical College Journal, 2015
Epilepsy is a complex disorder affecting brain function having a variety of contributing factors. The genetic predisposition plays a key role in the genesis of epilepsy. Antiepileptic drugs (AEDs) provide effective control in majority of patients with different seizure types. But some refractory cases and those who cannot tolerate the conventional AEDs, it is difficult to control the seizures adequately. On the basis of different mechanisms of action and considering the side effects of drugs, various newer approaches have been evolved during the recent years in the rational management of epilepsy. A brief account of these newer treatment modalities has been focused and incorporated in this review in order to enlighten the readers with the possible beneficial effect of this regimen and their limitations as well.
Emerging drugs for epilepsy and other treatment options
European Journal of Neurology, 2007
Epilepsies are amongst the most frequent chronic neurological conditions. Patients suffer from spontaneously recurring seizures because of sudden extensive electrical gray matter discharges. Although the current drug therapy allows many patients at least some degree of a satisfying course of the disease, a substantial number of patients remain without adequate seizure control. Reasons are either refractoriness to anticonvulsant drugs or intolerable drug-related side effects. Epilepsy surgery should be considered in these cases as possible treatment option. Nevertheless, a considerable rate of patients will not be suitable candidates or continue to have seizures despite surgery. Therefore there is a substantial need for better antiepileptic drugs. The aim of this review is to highlight currently emerging different treatment approaches which may ameliorate the perspectives of patients with difficult-to-treat epilepsies.
Editorial: Novel Perspectives in the Treatment of Epilepsy
Current pharmaceutical design, 2017
Epilepsy is a chronic neurological disorder affecting up to 1% of the population worldwide. Despite tremendous advances in the treatment of epilepsy, about 20% of patients are still unresponsive to the current available treatments. The intent of this thematic issue is to provide a comprehensive overview of recent advances in our understanding of the biological basis and modern clinical approaches to epilepsies, bridging the gap between the basic science and clinical implications. In the first chapter, Citraro et al. [1] review the recent findings on the role played by histone deacetylases and the possible function of different histone modifications in epilepsy and epileptogenesis. Histone modification regulates neurobiological processes such as neural network function, synaptic plasticity and synaptogenesis which also contribute to the pathophysiology of epilepsy. Inhibitors of histone deacetylases have been tested successfully in different experimental models of epilepsy. A variety of reports suggest an imbalance in excitatory and inhibitory neurotransmission as one of the pathophysiological mechanisms underlying the occurrence and progression of seizures. Palma et al. [2] review physiological, neuropathological and functional studies supporting the modulation of the activity of GABA A receptors (GABA A Rs), that are important targets of antiepileptic drugs (AEDs). Several inflammatory mediators (cytokines and chemokines) play an important role in the modulation of GABA A Rs. In addition, specific small noncoding RNAs, namely miRNAs, may regulate GABA A Rs, and they help in developing new therapeutic approaches based on the modulation of gene expression. The lack of treatments which can prevent epilepsy development or improve disease prognosis represents an unmet and urgent clinical need. Terrone et al. [3] review key preclinical and clinical findings supporting a role of brain inflammation in the pathogenesis of seizures. Understanding the role of neuroinflammation in seizure pathogenesis, the authors say, is instrumental for a mechanism-based discovery of selective therapies targeting the epilepsy causes rather than its symptoms, thereby allowing the development of novel disease-modifying treatments. The translation of laboratory findings in the clinic may also encourage researchers to test anti-inflammatory drugs already in medical use with other indications. Absence seizures are not always easy to treat. The most widely prescribed antiepileptic drugs (AEDs) for these seizure type, i.e. ethosuximide and valproic acid, are not always well tolerated or effective, and seizure freedom is far from being achieved in a small proportion of patients. The experimental treatment options for absence seizure are reviewed by van Luijtelaar et al. [4]. Cortical and/or thalamic excitability or the interaction between cortex and thalamus provides the rationale to the development of new anti-absence drugs, among others metabotropic glutamatergic positive and negative allosteric modulators. In addition, high frequency electrical subcortical or cortical stimulation might abort ongoing spike-wave discharges. Possibilities for prevention with real-time EEG analyses in combination with electrical stimulation might be a way to control seizures. Despite the availability of many new AEDs, for several patients with epilepsy, the quality of life and the therapeutic response remain unsatisfactory. Zaccara and Schmidt [5] provide a nice overview of drugs in clinical development. The authors divide the available compounds in two groups: 1) those initially developed for the treatment of diseases other than epilepsy 2) those specifically developed for the treatment of epilepsy. Among them, everolimus, and perhaps, fenfluramine are effective in specific epileptic diseases and may be considered true disease modifying drugs. With the exception of compounds such as cannabinidiol, cannabidivarin and minocycline, the vast majority of drugs in development have mechanisms of action similar to those of the anti-seizure drugs already in the market. The authors conclude that new drugs should thus be developed to specifically target the biochemical alteration which characterizes the underlying disease and also includes targets that contribute to epileptogenesis in relevant epilepsy models. Little is known about long-term safety and tolerability of several AEDs recently marketed. Palleria et al. [6] review the literature on this topic to highlight safety, tolerability and pharmacological interactions of the newest AEDs. According to the authors, treatment failure can be mostly explained by poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy. They conclude that the principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to the oldest drugs. As early detection of ADRs could lead to an improvement in patients' quality of life, ADRs should be actively monitored in the context of post marketing surveillance in the clinical practice setting. Clinicians need to become more aware of the potential dangers associated to co-prescription of AEDs and psychotropic agents. Spina and De Leon [7] provide an updated review of clinically relevant pharmacodynamic interactions between AEDs and psychotropic medications. In the light of the underlying pharmacodynamic mechanisms, the authors summarize potentially beneficial and dangerous pharmacodynamic interactions between AEDs and psychotropic drugs. They conclude that clinicians should be more aware of the potential for dangerous combinations of an increasingly frequent co-prescription of AEDs and psychotropic agents. AEDs therapy must be personalized according to patients' individual characteristics, including gender, age and psychiatric comorbidities. The relevance of these variables on AED choice has been nicely appraised by Pisani et al.
The clinical impact of new antiepileptic drugs after a decade of use in epilepsy
Epilepsy Research, 2002
The introduction of numerous effective, well tolerated and safe new antiepileptic drugs (AEDs) in the last decade of the 20th century has widened the choice of treatment options in epilepsy and improved the tolerability and the ease of use of treating patients with epilepsy. Nevertheless, significant safety and efficacy deficits continue to exist. Severe idiosyncratic reactions and organ toxicity have hampered the wide use of some of the newer AEDs. As a decade before, about one third of patients with chronic epilepsy is resistant to current pharmacotherapy. Even in patients in whom pharmacotherapy is efficacious, current AED do not seem to affect the progression or the underlying natural history of epilepsy. In addition, there is currently no drug available which prevents the development of epilepsy, e.g. after head trauma. Thus, there is an unmet need for safer and more effective drugs, especially for chronic, drug-resistant epilepsy. To stimulate the development of even better compounds, the demonstrated benefits and risks of current new AEDs are reviewed.
2012
Epilepsy is defined as episodic cerebral dysfunction due to increased excitability of brain cells that caused by various reasons. Anti-epileptic drugs (AED) cannot stop the mechanisms that cause epilepsy, but they can decrease the frequency of seizures or completely stop the seizures without causing a general depression in central nervous system while they are using. In this case report, we aimed to discuss the therapeutic way that physician chose, depending on personal experiences in patient that developed adverse effects to both old generation (phenytoin, valproic acid) and new generation (Vaigabatrine, Lamotirgine, Levetiracetam, Pregabaline) AEDs. Even though it needs to be careful when treating a patient with epilepsy to maximize the therapeutic efficacy and to prevent complications, we intended to emphasise that there are unknown parts of AED mechanisms. doi: http://dx.doi.org/ 10.4021/jnr167e