Clinical Pharmacology of Modern Antiepileptic Drugs

2017 ◽  
Vol 10 (6) ◽  
pp. 3875-3890
Author(s):  
D Samba Reddy
Keyword(s):  
Antiepileptic Drugs ◽  
Enzyme Induction ◽  
Epileptic Seizures ◽  
Drug Of Choice ◽  
Voltage Gated Sodium Channels ◽  
Intractable Seizures ◽  
Spread Of Excitation ◽  
Clonic Seizures ◽  
Excitability Of Neurons ◽  
Orally Active

This article describes current antiepileptic drugs (AEDs) that are available for treatment of epilepsy. Epilepsy is characterized by repeated occurrence of seizures.  Epileptic seizures are classified into focal and generalized types. Around two-dozen AEDs are available for treating epilepsy. AEDs act on diverse molecular targets to selectively modify the abnormal excitability of neurons by reducing the focal seizure discharges or preventing spread of excitation. AEDs suppress seizures by blocking the voltage-gated sodium channels (phenytoin, carbama-zepine, valproate, lamotrigine, oxcarbazepine, topiramate), voltage-activated calcium channels (ethosuximide, gabapentin), potentiation of GABA inhibition (barbiturates, benzodiazepines, tiagabine), and reduction of glutamate excitation (felbamate, parampanel). Carbamazepine, phenytoin, and valproate are the first-line agents for partial seizures and generalized tonic-clonic seizures. Ethosuximide is the drug of choice for absence seizures. AEDs are orally-active and show unique pharmacokinetic features. Some AEDs cause enzyme induction and hence produce drug-drug interactions. Newer AEDs such as gabapentin, levetiracetam, tiagabine, and pregabalin do not cause enzyme induction. Despite many advances in epilepsy research, nearly 30% of people with epilepsy have drug-resistant or intractable seizures. Presently, there is no cure for epilepsy. Thus, newer and better AEDs that can better prevent refractory seizures and modify the disease are needed for curing epilepsy.    

Clinical Pharmacology and Therapeutics of Antiepileptic Drugs

2020 ◽  
Vol 13 (6) ◽  
pp. 5165-5180
Author(s):  
Samba Reddy
Keyword(s):  
Antiepileptic Drugs ◽  
Enzyme Induction ◽  
Epileptic Seizures ◽  
Drug Of Choice ◽  
Voltage Gated Sodium Channels ◽  
Intractable Seizures ◽  
Spread Of Excitation ◽  
Refractory Seizures ◽  
Excitability Of Neurons ◽  
Orally Active

This article describes clinical antiepileptic drugs (AEDs) that are available for treatment of epilepsy. Epilepsy is characterized by repeated occurrence of seizures. Epileptic seizures are classified into focal onset (partial) and generalized onset (generalized) types. Around two-dozen AEDs are available for treating epilepsy. AEDs act on diverse molecular targets to selectively modify the abnormal excitability of neurons by reducing the focal seizure discharges or preventing spread of excitation. AEDs suppress seizures by blocking the voltage-gated sodium channels (phenytoin, carbamazepine, valproate, lamotrigine, oxcarbazepine, topiramate), voltage-activated calcium channels (ethosuximide, gabapentin), potentiation of GABA inhibition (barbiturates, benzodiazepines, tiagabine), and reduction of glutamate excitation (felbamate, parampanel). Carbamazepine, phenytoin, and valproate are the first-line agents for partial onset seizures and generalized onset seizures. Ethosuximide is the drug of choice for absence seizures. AEDs are orally-active and show unique PK features. Some AEDs cause enzyme induction and hence produce drug-drug interactions. Newer AEDs such as gabapentin, levetiracetam, tiagabine, and pregabalin do not cause enzyme induction. Despite many advances in AEDs, nearly 30% of people with epilepsy have drug-resistant or intractable seizures. Presently, there is no cure for epilepsy. Thus, newer and better AEDs that can better prevent refractory seizures and modify the disease are needed for curing epilepsy.

Clinical Pharmacology of Current Antiepileptic Drugs

2014 ◽  
Vol 7 (1) ◽  
pp. 2305-2319
Author(s):  
D. Samba Reddy
Keyword(s):  
Antiepileptic Drugs ◽  
Enzyme Induction ◽  
Neuronal Excitability ◽  
Clinical Manifestations ◽  
Epileptic Seizures ◽  
Induction Treatment ◽  
Drug Of Choice ◽  
Voltage Gated Sodium Channels ◽  
Intractable Seizures ◽  
Spread Of Excitation

This article describes current antiepileptic drugs (AEDs) that are available for treatment of epilepsy. Epilepsy is characterized by repeated occurrence of seizures, which are clinical manifestations of abnormal electrical discharges in the brain.  Epileptic seizures arise from a multiplicity of factors that regulate neuronal excitability and synchrony.  Epilepsy is caused because of certain genetic defects or acquired due to brain injury. Epileptic seizures are classified into partial (simple partial and complex partial) and generalized (absence, tonic-clonic, myoclonic, and atonic seizures) types. Around two-dozen AEDs, classified as standard and newer agents, are available for treating epilepsy. AEDs act on diverse molecular targets to selectively modify the abnormal excitability of neurons by reducing the focal seizure discharges or preventing spread of excitation. AEDs suppress seizures by blocking the voltage-gated sodium channels (phenytoin, carbamazepine, valproate, lamotrigine, oxcarbazepine, topiramate), voltage-activated calcium channels (ethosuximide, gabapentin), potentiation of GABA inhibition (barbiturates, benzodiazepines, tiagabine), and reduction of glutamate excitation (felbamate). Carbamazepine, phenytoin, and valproate are the first-line agents for partial seizures and generalized tonic-clonic seizures. Ethosuximide is the drug of choice for absence seizures. Intravenous benzodiazepines diazepam or lorazepam are effective in terminating status epilepticus. AEDs are orally-active and show unique pharmacokinetic features. Some AEDs cause enzyme induction and hence produce drug interactions. Newer AEDs such as gabapentin, levetiracetam, tiagabine, zonisamide and pregabalin do not cause enzyme induction. Treatment in pregnancy must consider optimizing therapy while preventing teratotoxicity of AEDs. There are alternative options (ketogenic diet) for children. Despite many advances in epilepsy research, nearly 30% of people with epilepsy have “intractable seizures” that do not respond to drug therapy. Presently, there is no cure for epilepsy. Therefore, newer and better AEDs that can better prevent seizures and modify the disease are needed for curing epilepsy.

scholarly journals Leucine-rich glioma-inactivated protein 1 antibody-mediated autoimmune encephalitis in a 4-year-old girl: a case report

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Junxia Luo ◽  
Jianguo Shi ◽  
Yehong Chen ◽  
Wandong Hu ◽  
Yujie Guo ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Case Report ◽  
Antiepileptic Drugs ◽  
Brain Magnetic Resonance Imaging ◽  
Autoimmune Encephalitis ◽  
Epileptic Seizures ◽  
Case Presentation ◽  
Csf Levels ◽  
Clonic Seizures ◽  
Magnetic Resonance Imaging Mri

Abstract Background Leucine-rich glioma-inactivated protein 1 (LGI1) antibody-mediated encephalitis is a rare subtype of autoimmune encephalopathy, which is associated with autoimmunity against the neuronal plasma membrane proteins. The characteristic symptoms of this disease are memory dysfunction, seizures, faciobrachial dystonic seizures, cognitive deficits, neuropsychiatric disturbances, and intractable hyponatremia. The diagnosis of this disease mainly depends on the presence of anti-LGI1 antibody in serum or cerebrospinal fluid of patients. LGI1 antibody encephalitis has been reported mostly in adults, with rare occurrences in children. Case presentation In this report, we described a 4-year-old girl with typical seizures. Seizure types included focal seizures and generalized tonic-clonic seizures. The electroencephalogram findings showed focal discharges. Brain magnetic resonance imaging (MRI) showed normal. The cerebrospinal fluid (CSF) levels of cells, glucose, and chloride were within the normal range, and the culture did not reveal growth of any pathogen. Test of serum LGI1-Ab was positive, while the tests for autoimmune encephalitis antibody series in CSF were negative. The seizures of the patient were completely controlled after the therapy of immunoglobulin, methylprednisolone and antiepileptic drugs (AEDs), and the mental state almost returned to normal. Conclusion To our knowledge, the patient described here may be the youngest case of LGI1 antibody encephalitis reported to date. Children with the LGI1 antibody-associated encephalitis may present only with single symptoms such as epileptic seizures and have good response to the therapy of immunoglobulin, methylprednisolone and antiepileptic drugs. Our case report will provide hints for pediatricians in the diagnosis and treatment of LGI1-antibody encephalitis.

Pregnancy in women with epilepsy

2017 ◽  
pp. 61-64
Author(s):  
Shahla Yagub Melikova ◽  
Keyword(s):  
Key Words ◽  
Antiepileptic Drugs ◽  
Congenital Malformations ◽  
Social Problems ◽  
Neurological Diseases ◽  
Epileptic Seizures ◽  
Conclusive Evidence ◽  
High Dose ◽  
Key Words Pregnancy

Epilepsy is one of the most common serious neurological diseases. Many publications relating to interaction of epilepsy and pregnancy have been studied. Women with epilepsy experience a number of physical and social problems associated with obstetric risk, the risk of seizures during pregnancy. Generalized epileptic seizures may have a direct damaging effect on the fetus, although there is no conclusive evidence for a significant increase in the incidence of complications during pregnancy in women with epilepsy. Antenatal exposure to antiepileptic drugs, especially in high-dose and polytherapy, increases the risk of congenital malformations. There are concerns regarding the effects of antiepileptic drugs on infants during breastfeeding. However, the risk of complications associated with the epilepsy and the effects of antiepileptic drugs on the fetus may be reduced by joint monitor by neurologist-epileptologist and obstetrician. Key words: pregnancy, antiepileptic drugs, epilepsy, monotherapy, polytherapy.

scholarly journals Assessing efficacy and safety of rectally vs. intravenously administered Sibazon in treatment of generalized epileptic seizures in children

2021 ◽  
Vol 13 (3) ◽  
pp. 200-210
Author(s):  
A. G. Prityko ◽  
K. V. Osipova ◽  
P. L. Sokolov ◽  
E. A. Ezhova ◽  
I. G. Kotel’nikova ◽  
...  
Keyword(s):  
Drug Administration ◽  
Epileptic Seizures ◽  
Blood Analysis ◽  
Intramuscular Administration ◽  
Final Visit ◽  
Fisher Exact Test ◽  
Efficacy And Safety ◽  
Clonic Seizures ◽  
Group 2 ◽  
Group 1

Objective: to prove the therapeutic equivalence and similar safety profile of “Sibazon, rectal solution” (international nonproprietary name: diazepam) and “Sibazon, solution for intravenous and intramuscular administration” in children with primary generalized and bilateral tonic, clonic and tonic-clonic seizures.Material and methods. An open-label, randomized clinical trial on efficacy and safety was conducted in 20 patients suffering from epilepsy with generalized seizures aged 1 to 17 years. Clinical blood and urine tests, biochemical blood analysis were used for diagnostics (glucose, total protein, albumin, total bilirubin, cholesterol, aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, alkaline phosphatase, creatinine, urea, creatinine clearance), as well as data on electrocardiographic (ECG) and electroencephalographic (EEG) studies. The patients were divided into two groups: in Group 1 (n=8), a rectal solution was used, in Group 2 (n=12) – a solution for intravenous and intramuscular administration.Results. The number of cases in which seizures were completed within 10 minutes after using the drug without resuming within subsequent 60 minutes, in Group 1 was 7 (87.5%), and in Group 2 – 9 (75.0%) (Fisher exact test (FET): p=0.617). Repeated primary generalized or bilateral tonic/clonic/tonic-clonic seizures within 24 hours after drug administration, in Group 1 were absent in 5 (62.5%) patients, in Group 2 – in 6 (50%) (FET: p=0.670); within 48 hours after drug administration – in 5 (62.5%) and 7 (58.3%) children, respectively (FET: p=1.00). Physical examination revealed no pathology in all patients at the final visit. While comparing ECG and EEG data at the final visit, no inter-group differences were found by the number of children with deviations from the norm. The results of laboratory studies confirmed that using the studied drugs had no negative effect on the main indicators of clinical and biochemical blood tests as well as clinical urine analysis.Conclusion. The effectiveness of the rectal form of Sibazon in relieving pediatric generalized epileptic seizures is comparable to that of Sibazon for intramuscular administration. The drug rectal form, due to easy-to-use administration, is preferable for outpatient practice. “Sibazon, rectal solution” is safe and has good tolerability.

scholarly journals Juvenile myoclonic epilepsy: current state of the problem

2021 ◽  
Vol 1 (2) ◽  
pp. 2-20
Author(s):  
N. A. Shnayder ◽  
K. V. Petrov
Keyword(s):  
Primary Care Physicians ◽  
Epileptic Seizures ◽  
Juvenile Myoclonic Epilepsy ◽  
Historical Significance ◽  
Current State ◽  
High Prevalence ◽  
Clonic Seizures ◽  
Generalized Epilepsy ◽  
Genetically Determined ◽  
Selection Of

Due to the high prevalence of the disease, its genetic and clinical heterogeneity, the need for lifelong therapy and the emergence of new views on the pathogenesis and course of JME, it is necessary to provide primary care physicians (general practitioners, district therapists, neurologists) with up-to-date systematized information about the most common form of genetic generalized epilepsy (Herpin-Janz syndrome). JME is a genetically determined disease of the brain, accompanied by a triad of seizures (absences, myoclonia, generalized tonic-clonic seizures), and developing mainly in adolescence and young age. In recent years, monogenic and multifactorial forms of JME have been identified, but questions about the genetics of JME are far from being resolved. JME is characterized by the preservation of intelligence, life expectancy with adequate therapy does not differ from the average population, but the frequency of failures of pharmaco-induced remission is high when taking anticonvulsants is canceled. This explains the need for lifelong pharmacotherapy, individual selection of anticonvulsants. About 30% of patients with JME have non-psychotic mental disorders, disorders of the sleep and wake cycle, which in turn leads to an aggravation of epileptic seizures mainly in the first half of the day. This review presents an analysis of full-text publications in Russian and English over the past five years in the databases eLibrary, PubMed, Web of Science, OxfordPress, Springer, and Clinicalkeys. In addition, the review includes earlier publications of historical significance.

scholarly journals MAHA PANCHAGAVYA GHRITA IN APASMARA (EPILEPSY) – A KETOSIS PERSPECTIVE

2020 ◽  
Vol 8 (9) ◽  
pp. 4569-4572
Author(s):  
Usha K S ◽  
Gurdip Singh
Keyword(s):  
Effective Treatment ◽  
Ketogenic Diet ◽  
Butyric Acid ◽  
Epileptic Seizures ◽  
Gamma Amino Butyric Acid ◽  
Serum Electrolytes ◽  
Sodium Potassium ◽  
Inhibitory Neurotransmitters ◽  
Amino Butyric Acid ◽  
Drug Of Choice

Epileptic seizures are caused due to imbalance in the excitatory and inhibitory neurotransmitters. Serum electrolytes like sodium, potassium and calcium play a key role in maintaining the epileptic threshold. In the quest of effective treatment in epilepsy ketogenic diet has been promising. It is found to increase the inhibitory Gamma amino butyric acid and thus increase the epileptic threshold. In this context Maha Panvhagavya Ghrita recommended in the treatment of Apasmara seems to be the drug of choice.

Disulfiram-induced epileptic seizures

2021 ◽  
Vol 14 (3) ◽  
pp. e236296
Author(s):  
Violeta Nogueira ◽  
Mafalda Azevedo Mendes ◽  
Inês Pereira ◽  
Joana Teixeira
Keyword(s):  
Adverse Effect ◽  
Side Effects ◽  
Alcohol Consumption ◽  
Alcohol Dependence ◽  
Male Patient ◽  
Epileptic Seizure ◽  
Therapeutic Agent ◽  
Epileptic Seizures ◽  
Clinical Complications ◽  
Clonic Seizures

Disulfiram has been widely used for over six decades in the treatment of alcohol dependence, as an aversive therapeutic agent. Despite having very few side effects when taken without concurrent alcohol consumption, some of these may underlie serious clinical complications. Epileptic seizure induction is a rare adverse effect of disulfiram and its aetiological mechanism is unknown. We present a hospitalised 47-year-old male patient with two episodes of generalised tonic-clonic seizures during treatment with disulfiram while abstinent from alcohol.

scholarly journals OS3.1 Antiepileptic drugs and their association with depression, anxiety and subjective cognitive impairment in glioma patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii8-iii8
Author(s):  
P B van der Meer ◽  
M J B Taphoorn ◽  
M J van den Bent ◽  
L Dirven ◽  
J A F Koekkoek
Keyword(s):  
Valproic Acid ◽  
Cognitive Impairment ◽  
Antiepileptic Drugs ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Depression Scale ◽  
Epileptic Seizures ◽  
Common Symptom ◽  
Subjective Cognitive Impairment ◽  
Confounding Variables

Abstract BACKGROUND Epileptic seizures are a common symptom in glioma patients and generally treated with antiepileptic drugs (AEDs), which are considered to have the potential of mood-modulating and neurocognitive adverse effects. This observational study aimed to assess the independent association between AEDs and depression, anxiety and subjective cognitive impairment in glioma patients. MATERIAL AND METHODS Use of AEDs was defined as a categorical variable (none or at least one). Depression and anxiety were measured with the Hospital Anxiety and Depression Scale, while subjective cognitive impairment was measured with the Medical Outcomes Study-Cognitive Functioning Scale. Hierarchical multivariable logistic regression analyses were performed for each outcome separately. Besides use of AEDs, other confounding variables such as seizure severity and Karnofsky Performance Status score were included. Analyses were repeated for the two most commonly prescribed AEDs separately, levetiracetam or valproic acid, with the same confounding variables. RESULTS A total of 272 grade II-IV glioma patients were included in the study, of which 68% used at least one AED. Prevalence of depression was 10% for patients taking 0 AEDs and increased significantly to 21% (adjusted Odds Ratio [aOR]=2.4 [95%Confidence Interval {CI}=1.0–5.8]) for those taking ≥1. Prevalence was not significantly different between patients using 0 and using ≥1 AEDs for both anxiety (19% versus 26%, aOR=1.1 [95%CI=0.6–2.2]) and subjective cognitive impairment (16% versus 21%, aOR=1.2 [95%CI=0.6–2.5]). Although prevalences of depression (13% versus 23%, aOR=1.6 [95%CI=0.8–3.2]) and anxiety (17% versus 31%, aOR=1.8 [95%CI=0.9–3.3]), but not subjective cognitive impairment (20% versus 18%, aOR=1.7 [95%=0.4–1.4]), differed significantly between patients not using and using levetiracetam, these associations were not independent. No significant differences were found between patients not using and using valproic acid on the three outcome measures. CONCLUSION After adjustment of confounders, only depression was associated with the use of AED’s. No such relation was found for anxiety or subjective cognitive impairment. Use of levetiracetam or valproic acid were not independently related to depression, anxiety or subjective cognitive impairment.

Antiepileptic drugs and behaviour: mechanisms of action

2018 ◽  
Author(s):  
Andrea E. Cavanna
Keyword(s):  
Antiepileptic Drugs ◽  
Neuronal Excitability ◽  
Epileptic Seizures ◽  
Mechanisms Of Action ◽  
Neuronal Membrane ◽  
Pharmacological Properties ◽  
Glutamatergic Neurotransmission ◽  
Gabaergic Neurotransmission ◽  
Voltage Gated ◽  
Voltage Gated Channels

Antiepileptic drugs (AEDs) exert their pharmacological properties on both epileptic seizures and behaviour through different mechanisms of action. These include modulation of ion (mainly sodium and calcium) conductance through voltage-gated channels located within the neuronal membrane, as well as facilitation of inhibitory (GABAergic) neurotransmission and inhibition of excitatory (glutamatergic) neurotransmission, resulting in regulation of neuronal excitability.

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