Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Determining antiepileptic drug (AED) concentration in biological fluids and calculating its dosage on this basis is a long-term method in the treatment of epilepsy. This facilitates the treatment and increases the safety of patients in the aspect of suitable seizure control and reduced risk of side effects. This report presented the range and the number of antiepileptic drug concentration determined during thirteen years activity of Laboratory of Clinical Neuropharmacology in the Department of Developmental Neurology. There was also a number of drug concentrations particularly often determined presented, compared and discussed. Moreover, there were also analyses of subtherapeutic, therapeutic and potentially toxic concentration decomposition presented for subsequent AEDs. The frequency of conventional drug and of slow released forms for VPA and CBZ was compared. VPA appeared to be the most frequently monitored drug and CBZ occurred to be the next one. The concentrations of PHT, PB, PRM and ETH were more rarely determined. In the observed period of time the number of LPP concentration determined in the therapeutic range amounted to 69%, the least frequently the potentially toxic levels were determined--11%. Normal concentrations i.e. therapeutic ones were most often determined for CBZ (77%) and subtherapeutic levels were determined mostly for PHT.
 ...
PMID:[Therapeutic antiepileptic drug monitoring: thirteen years of experience in the Laboratory of Clinical Neuropharmacology in the Chair and Department of Developmental neurology]. 1076 45

The authors presented the results of treatment with lamotrigine (LTG, Lamictal) in 13 patients with drug resistant epilepsy (add-on therapy). There were 8f, 5m. aged 16-60 years, mean age 28.8 years. Generalized seizures occurred in 8 patients (62%). In this group there was 1 patient (aged 16 years) with the Lennox-Gastaut syndrome and 1 patient (aged 20 years) with valproate resistant juvenile myoclonic epilepsy. Complex partial seizures and complex partial with secondary generalization occurred in 5 patients (38%). Before LTG addition mean seizure frequency was from 3/month to several times/day. The mean duration of epilepsy was 16.6 years. The 8 patients were treated with CBZ and VPA, one with PHT and VPA, one CBZ and VGB. Monotherapy with VPA was introduced in 3 patients. After 6 months of treatment with LTG the efficacy was evaluated. 12 patients took LTG with VPA, 1 LTG with CBZ. Complete reduction of seizures was achieved in 3 cases (23%), at least 50% reduction in 3 patients (23%), reduction below 50% in 4 patients (31%). In 3 cases (23%) the results of treatment were negative (increase or no change in seizure frequency). Beneficial psychotropic effect was observed in 9 patients (69%). Adverse effects occurred in 2 patients (15%). Headache, vertigo, sleepness were observed in one case. Rash occurred in 1 patient (treated with LTG and VPA). After 6 months 3 patients were excluded from the study because of negative effects of treatment. LTG is helpful and well tolerated in drug-resistant epilepsy.
 ...
PMID:[Lamotrigine in add-on therapy: assessment of efficacy in drug resistant epilepsy]. 1084 3

Many epileptic patients suffer from cognitive impairments; both the underlying pathology and antiepileptic drug therapy can cause such deficits. Phenytoin, one of the widely used anticonvulsants, is known to adversely affect cognitive function. A reputed Indian nootropic plant Bacopa monniera (BM) was evaluated alone and in combination with phenytoin for its effect on (a) passive-avoidance (PA) task; (b) maximal electroshock seizures; and (c) locomotor activity in mice. Phenytoin (PHT, 25 mg/kg po x 14 days) adversely affected cognitive function in the PA task. BM extract (40 mg/kg x 7 days), given along with phenytoin in the second week of the two-week regimen, significantly reversed PHT-induced impairment. Both acquisition and retention of memory showed improvement without affecting its anticonvulsant activity. The observed cognitive effects of PHT and BM were found to be independent of motor stimulation. The results provide evidence for potential corrective effect of BM in cognitive deficit associated with PHT therapy.
 ...
PMID:Protection from phenytoin-induced cognitive deficit by Bacopa monniera, a reputed Indian nootropic plant. 1094 May 74

This study was undertaken to elucidate the anticonvulsive effects of zonisamide (ZNS: 25, 50, and 75 mg/kg, intraperitoneal [i.p.]), which was coadministered with valproic acid (VPA: 25, 50, and 100 mg/kg, i.p.), or phenytoin (PHT: 10, 25, and 50 mg/kg, i.p.) to ZNS concentration, nitric oxide metabolites (NOx levels), and monoamines in the brain of the EL mouse, a strain highly susceptible to seizures. NOx levels were obtained from measuring of combined level of nitrite plus nitrate. Coadministration of ZNS with VPA or PHT suppressed convulsive seizures more effectively than with treatment of ZNS alone. Both serum and brain concentrations of ZNS tended to increase as the dose of VPA or PHT was increased. While coadministrations of ZNS (75 mg/kg) and VPA or PHT at any dose did not change brain and serum NOx levels, those altered brain monoamine contents. These results suggested that anticonvulsive effect of coadministrations of ZNS and VPA or PHT were caused by changes of monoamines rather than changes of NO metabolites.
 ...
PMID:Effects of combined administration of zonisamide and valproic acid or phenytoin to nitric oxide production, monoamines and zonisamide concentrations in the brain of seizure-susceptible EL mice. 1104 98

Epileptic nystagmus (EN) is an uncommon phenomenon characterized by repetitive and rapid saccades, in association with epileptic discharges. We present a critical video-EEG recording in a patient with occipital seizures that appeared clinically as EN. The subject, male, 70 years-old, was examined because of generalized tonic-clonic seizures, preceded by left cephalic version. These were controlled using i.v. PHT, but partial seizures persisted, which we recorded using video-EEG. Clinically, we observed episodes of left conjugate deviation of the eyes, accompanied by horizontal nystagmoid movements, with a rapid leftward component and visual hallucinations. The patient did not lose consciousness. Ictal EEG: spike rhythm in the posterior right occipito-temporal region extending to adjacent and contralateral regions, followed by post-discharge of slow waves. The video-EEG was interpreted as partial oculo-clonic status epilepticus of right temporo-occipital origin. Cranial MRI: old, bilateral hemorrhaging occipital contusions associated with previous cranial injury. The picture persisted for two days, and disappeared with administration of CBZ 600 mg/d. Our patient's nystagmus seemed to be related to the critical activity recorded in the right occipito-temporal region. The co-existence of visual hallucinations and the video-EEG correlation support this possibility. This phenomenon is probably due to epileptic activation of the cortical center of saccadic movements, with a rapid phase of nystagmus, contralateral to the focus, and a slow ipsilateral phase in association with a defect in the gaze-fixing system ("leaky neural integrator") [published with videosequences].
 ...
PMID:Epileptic nystagmus: a case study video-EEG correlation. 1196 76

Of 362 children with therapy-resistant epilepsy, 119 patients had generalized tonic seizures, which were the most common seizure type in patients with generalized epilepsy. The long-term observation of the patients with tonic seizures revealed that their seizures were completely controlled in 27 patients for more than 5 years. The effective antiepileptic drugs were VPA (10 patients), PHT (5), CLB (4), ZNS (2), VPA + PHT (4), ZNS + CLB (1) and VPA + AZA (1). For obtaining improvement of tonic seizures, another strong factor is reducing the number of antiepileptic drugs, such as the average number of drugs, which was 4.7 to 2.4 in these 27 patients.
 ...
PMID:Therapy-resistant epilepsy in children: with the view of the long-term outcome. 1514 7

Oxcarbazepine (OXC) was introduced in 1990 and is now registered in 54 countries worldwide as monotherapy, as add-on treatment for partial seizures, with or without secondarily generalised seizures, and primary generalised tonic-clonic seizures. OXC and its active metabolite, monohydroxy derivative (MHD), block voltage-dependent sodium channels and may effect potassium and calcium channels. In animal models of epilepsy, OXC and MHD have efficacy similar to that of CBZ. There is no evidence for clinically important teratogenicity, mutagenicity or carcinogenicity. OXC has no effect on serum concentrations of hepatically metabolised anti-epileptic drugs (AEDs) and no clinically important interactions with common non-AEDs, other than hormonal contraceptives. MHD has low protein binding and linear pharmacokinetics. Adverse effects (AEs) are usually related to the central nervous system. Approximately three-quarters of patients who experience adverse effects with CBZ improve when switched to OXC, without loss of seizure control. The incidence of rash appears to be less than that expected with CBZ. While hyponatraemia may occur more often with OXC than with CBZ, it is rarely symptomatic. OXC is an effective and safe drug for the treatment of partial-onset and primary generalised tonic-clonic seizures. Placebo- and low-dose controlled double-blind monotherapy studies prove that OXC has anticonvulsant activity and that therapeutic dosages may be obtained with a 24 h titration in hospitalised patients, if necessary. Comparative double-blind trials show that OXC has similar efficacy to VPA, CBZ and PHT, but has advantages compared to those agents in terms of pharmacokinetics, side-effects and tolerability.
 ...
PMID:Oxcarbazepine: current status and clinical applications. 1599 10

The idiopathic generalized epilepsies (IGE) are a group of epilepsies that are genetically determined, have no structural or anatomic cause, and usually begin early in life. Neurologic examination, intelligence, and imaging studies are normal, and EEG shows only epileptiform abnormalities (i.e., no abnormal slow activity or evidence for diffuse encephalopathy). In some IGE, the genetic substrate has been identified, whereas in most, it remains unknown. Depending on the age at onset and predominant seizure type, individual subtypes of IGE (syndromes) are defined. However, overall, there are more similarities than there are differences among the various subtypes, and the IGE are best viewed as a spectrum or continuum of conditions. In general, IGE respond to treatment, with 80-90% becoming fully controlled. However, not all antiepileptic drugs (AED) are equally effective in IGE. Some AED are ill advised because they either do not work or exacerbate seizure types other than generalized tonic-clonic (GTC) seizures, that is, absence and myoclonic seizures. These include carbamazepine, oxcarbazepine, phenytoin, gabapentin, and tiagabine. Their use is the main cause of "pseudo-intractability," and at least in the United States where PHT and CBZ are the most commonly used AEDs, patients with IGE are often on inadequate medications. For patients with clear IGE, the drug of choice is generally valproic acid because it effectively controls absence myoclonic seizures and GTC seizures. Second-line drugs (when first-line drugs fail or are not tolerated) may include benzodiazepines, but the use of second-line drugs is evolving rapidly. Some of the newer AEDs are considered broad spectrum, meaning that they work in IGE and focal epilepsies, although the evidence is largely preliminary at this point. These newer AEDs include lamotrigine, topiramate, levetiracetam, and zonisamide.
 ...
PMID:Practical management issues for idiopathic generalized epilepsies. 1630 86

This study examined the interaction characteristics between loreclezole (LCZ) and various conventional antiepileptic drugs (phenytoin--PHT, carbamazepine--CBZ, valproate--VPA and phenobarbital--PB) in the mouse maximal electroshock (MES)-induced seizure model using isobolographic analysis. Drug-related adverse effects were ascertained by use of the chimney test (motor impairment) and the step-through passive avoidance task (learning and retrieval). It was observed that the combination of LCZ with VPA or PB, at the fixed ratio of 1:1, was supra-additive (synergistic) and the combination of LCZ with CBZ, at all fixed ratios tested (1:3, 1:1 and 3:1), was supra-additive against electroconvulsions. The remaining combinations evaluated, i.e., LCZ with PB or VPA at fixed ratios of 1:3 and 3:1, as well as all fixed-ratio combinations between LCZ and PHT, were additive in the MES test in mice. Pharmacokinetic characterization revealed that LCZ significantly increased both free plasma and brain concentrations of CBZ and PHT, but was without effect on PB. Moreover, a bi-directional pharmacokinetic interaction between LCZ and VPA was observed in that while LCZ increased free plasma, but not total brain VPA concentrations, VPA increased the total brain, but not free plasma LCZ concentrations. Adverse-effect testing revealed that for all antiepileptic drug combinations neither motor performance nor long-term memory was altered. Of the drug combinations investigated, only that of LCZ and PB at the fixed ratio of 1:1 was not associated with any pharmacokinetic interactions, and thus it may be concluded that the supra-additive (synergistic) isobolographic interaction was pharmacodynamic in nature. Furthermore, the fact that LCZ and PB have similar mechanisms of action would suggest that drugs with similar mechanisms of action may provide rational polytherapy regimens.
 ...
PMID:Isobolographic analysis of interactions between loreclezole and conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model. 1660 39

Pharmacoresistance in epileptic patients may be ascribed to at least two, not mutually exclusive, mechanisms: a pharmacokinetic mechanism and a decreased sensitivity or availability of targets to antiepileptic drugs (AEDs; i.e., carbamazepine and phenytoin (CBZ, PHT)). Brain:plasma drug concentration ratios were determined intraoperatively during lobectomies performed to alleviate drug-resistant seizures. The brain:plasma ratio of CBZ was 1.48 when therapeutic serum levels (15-34 microM) were achieved. When concentrations of CBZ found in multiple-drug-resistant brain were directly applied to human cortical slices from drug-resistant patients made hyperexcitable and hypersynchronous by Mg(2+)-free media, bursting frequency was not significantly affected and overall excitability was reduced by 40%. Similar results were obtained for PHT. At higher AED concentrations (60-200 microM), a dose-dependent decrease of bursting frequency and amplitude was observed. Slices from drug-resistant epileptic patients made hypersynchronous/hyperexcitable by elevated potassium or inhibition of GABA-A receptors behaved similarly. Of note is the response of slices from human multiple-drug-resistant brain, which was greater than in rodent cortex from naive animals. Taken together, our results support the hypothesis that multiple drug resistance to AEDs involves cerebrovascular changes that impede the achievement of appropriate drug levels in the central nervous system.
 ...
PMID:In vitro responsiveness of human-drug-resistant tissue to antiepileptic drugs: insights into the mechanisms of pharmacoresistance. 1663 25


<< Previous 1 2 3 4 5 Next >>