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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Major cohort studies document that the long-term prognosis for most children with febrile convulsions (FC) is excellent. The 2 main treatment alternatives so far have been long-term prophylaxis with phenobarbital or valproate or no prophylaxis at all. Phenobarbital at times of fever is ineffective and obsolete. Consensus has emerged that long-term prophylaxis with antiepileptic drugs is rarely justified in FC considering the side effects and the favourable prognosis. No treatment at all does not appear quite satisfactory either, as FC have a high recurrence rate, disrupt family life and may have emotional consequences for the family. Moreover, all FC children face a risk, although admittedly low, of subsequent long-lasting potentially central nervous system (CNS)-damaging seizures. However, 2 further options exist: treatment with rapid-acting benzodiazepines solely at times of greatest risk, i.e., at high fever or at renewed seizures. Several clinical trials have confirmed that intermittent diazepam prophylaxis by way of a few doses of the drug per year provides effective seizure control and reduces the recurrence rate by one half or two thirds. The treatment is feasible and cheap, well tolerated by the child and well accepted by the parents. Compliance problems are common and only partly abatable. Trivial side effects are frequent. Transient respiratory apnoea does occur, but 15 years' experience substantiates that serious side effects are remarkably rare. Acute anticonvulsant treatment with rectal diazepam in solution given by the parents to stop ongoing seizures and to prevent immediate recurrences is an attractive alternative. It is feasible, is probably effective and minimizes the use of drugs, but compliance problems are common and protracted seizures are not always controlled. The subsequent management should include a risk profile approach considering a combination of risk factors for new FC rather than a single factor. By means of a risk index, based on simple clinical data including age at onset, family seizure history, seizure type and frequency of fever, children may be identified as being at low, intermediate or high risk for further febrile fits. However, risk factors for new FC and not for subsequent epilepsy should be used. It is concluded that preventing or abbreviating new FC with benzodiazepines appears to be a useful, although not ideal, drug-minimizing approach in managing many children with simple or complex FC. From a health hazard viewpoint, treatment is not strictly mandatory, although advisable. A selective strategy seems rational. Intermittent diazepam prophylaxis may preferably be offered to children at high risk for new FC.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intermittent diazepam prophylaxis in febrile convulsions. Pros and cons. 185 81

The substantia nigra (SN) is thought to be involved in the regulation of seizure activity and there is evidence that the nigra might be a site of anticonvulsant drug action, especially in the case of drugs that act by potentiating gamma-aminobutyric acid (GABA)-mediated neurotransmission. The current studies monitored the anticonvulsant effect of four major antiepileptic drugs, i.e. valproic acid, carbamazepine, phenobarbital and diazepam, in fully kindled rats before and after bilateral destruction of the SN. Rats were kindled by stimulation of either the basolateral amygdala or the piriform cortex. The SN was lesioned bilaterally by microinjection of ibotenic acid, and only animals with near-complete, selective destruction of the SN were used for final evaluation of the anticonvulsant drug experiments. The behavioural characteristics and the duration of fully kindled seizures were not altered by bilateral destruction of the SN. Phenobarbital, diazepam and valproate significantly reduced kindled seizures severity and duration before and after the SN lesions. Carbamazepine was the only drug to show a marked decrease in its anticonvulsant effects after SN lesion. Since benzodiazepines, valproate and phenobarbital are though to enhance GABAergic transmission, the lack of effect of SN lesions on the anticonvulsant effects of these drugs argues against the suggestion that the SN is the anatomical site responsible for exerting anticonvulsant effects in response to drug-induced augmentation of GABA transmission.
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PMID:Effect of selective bilateral destruction of the substantia nigra on antiepileptic drug actions in kindled rats. 196 44

Agonists acting at subtypes of glutamate receptors, N-methyl-D-aspartate, kainate and quisqualate, induce convulsions in rodents. Clonic seizures induced in mice by intracerebral administration of N-methyl-D-aspartate, kainate or quisqualate were used to study the anti- and proconvulsant potential of antiepileptic drugs and beta-carbolines. Systemic administration showed that the benzodiazepines clonazepam and midazolam blocked convulsions induced by kainate and had no effect on seizures triggered by N-methyl-D-aspartate and quisqualate. In contrast, diazepam blocked convulsions induced by either excitatory amino acid, as did valproate. The benzodiazepine receptor agonist beta-carboline ZK 93423 blocked convulsions induced by kainate but had no effect on seizures induced by N-methyl-D-aspartate or quisqualate. The antagonist beta-carboline ZK 93426 did not affect convulsions induced by excitatory amino acids, while the inverse agonists FG 7142 and ethyl-beta-carboline-3-carboxylate increased the sensitivity of mice to kainate. Phenobarbital and 2-chloroadenosine protected mice against seizures induced by quisqualate and kainate, while baclofen was active against convulsions produced by kainate. MK-801 selectively blocked convulsions induced by N-methyl-D-aspartate, and enhanced the susceptibility of mice to seizures triggered by kainate and quisqualate. Ethosuximide increased the susceptibility of mice to N-methyl-D-aspartate and had little or no effect on other types of seizures. Diphenylhydantoin enhanced the convulsant potential of quisqualate. Trimethadione and carbamazepine did not affect convulsions induced by N-methyl-D-aspartate, kainate or quisqualate. Intracerebral administration of midazolam protected mice against seizures induced by kainate. Ethosuximide increased the susceptibility of mice to N-methyl-D-aspartate, while diphenylhydantoin to quisqualate convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of antiepileptic drugs and beta-carbolines on seizures induced by excitatory amino acids. 209 26

A patient of pyridoxine dependent seizures was reported. He was born at 34 weeks' gestation and weighted 2,760 g. Apgar scores were 6 and 9 at 1 and 5 minutes, respectively. He showed the first seizure 2 hours after his birth. Phenobarbital, phenytoin, sodium valproate, diazepam and clonazepam were not effective. Pyridoxal phosphate (50 mg) was given intravenously, resulting in suppression of convulsions. However, muscle tonus was severely depressed. In EEG, a discontinuous pattern was found in quiet and indeterminate sleep on the 2nd day of life. At 5th week multifocal spikes were found, and the discontinuous pattern persisted. Ictal discharges at 13th week showed generalized, continuous, irregular and high voltage slow waves with multifocal spikes. At 27th week of life, high voltage slow waves disappeared and multifocal spike discharges decreased. At 2 years and 10 months of age, the patient was suffering from athetotic cerebral palsy and severe mental retardation. Pyridoxal phosphate at the doses of 35-40 mg/kg/day had been administered. Irritability sometimes occurred and additional 50 mg of pyridoxal phosphate controlled this irritability effectively.
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PMID:[Chronological change of EEG findings in a case of pyridoxine dependency seizures]. 222 90

Phenobarbital is widely used in the treatment of children with febrile seizures, although there is concern about possible behavioral and cognitive side effects. In 217 children between 8 and 36 months of age who had had at least one febrile seizure and were at heightened risk of further seizures, we compared the intelligence quotients (IQs) of a group randomly assigned to daily doses of phenobarbital (4 to 5 mg per kilogram of body weight per day) with the IQs of a group randomly assigned to placebo. After two years, the mean IQ was 7.03 [corrected] points lower in the group assigned to phenobarbital than in the placebo group (95 percent confidence interval, -11.52 to -2.5, P = 0.0068 [corrected]). Six months later, after the medication had been tapered and discontinued, the mean IQ was 5.2 points lower in the group assigned to phenobarbital (95 percent confidence interval, -10.5 to 0.04, P = 0.052). The proportion of children remaining free of subsequent seizures did not differ significantly between the treatment groups. We conclude that phenobarbital depresses cognitive performance in children treated for febrile seizures and that this disadvantage, which may outlast the administration of the drug by several months, is not offset by the benefit of seizure prevention.
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PMID:Phenobarbital for febrile seizures--effects on intelligence and on seizure recurrence. 237 71

Antiepileptic drug selection is based on efficacy for specific seizure types and epileptic syndromes. For idiopathic generalized epilepsies with absence, tonic-clonic, and myoclonic seizures, the drug of choice is valproate. Secondary generalized epilepsies with tonic, atonic, and other seizure types are difficult to treat with any single drug or combination of drugs. The drugs of choice for absence seizures are ethosuximide and valproate. For control of tonic-clonic seizures, any of the other major antiepileptic drugs can be effective. If valproate cannot be used, carbamazepine, phenobarbital, phenytoin, or primidone is effective, but ethosuximide or a benzodiazepine needs to be added to control associated absence or myoclonic seizures. The drugs of first choice for partial epilepsies with partial and secondarily tonic-clonic seizures are carbamazepine and phenytoin. Increasing evidence suggests that valproate may be a third alternative. Phenobarbital and primidone are second choice selections because of side effects. A combination of two of these five major antiepileptic drugs may be necessary for inadequately controlled patients. Other epilepsy syndromes such as neonatal and infantile epilepsies, febrile epilepsy, and alcoholic epilepsy require specific drug treatment. For all these seizure types and epilepsy syndromes, treatment ultimately must be selected to provide maximal efficacy and minimal adverse effect for each individual patient.
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PMID:Selection of drugs for the treatment of epilepsy. 228 35

Plasma phenytoin and phenobarbitone levels were estimated in 123 adult Ethiopian epileptics by gas-liquid chromatography. Thirty four (38.2%) of the patients on phenytoin, and 52 (52%) of those on phenobarbitone, had plasma levels in the conventional therapeutic ranges of 10-20 micrograms/ml and 10-30 micrograms/ml respectively. Of the 89 patients who were taking phenytoin either singly or combined with phenobarbitone, motor disturbances (ataxia and nystagmus) were seen in 31 (34.8%) and dysmorphic and idiosyncratic side effects including gum hypertrophy, hirsutism, acne and skin rash in 37 (41.6%). Subnormal serum calcium levels were noted in 15 (30.6%) and high alkaline phosphatase was found in 13 (26.5%). Phenobarbitone was found to be an effective anticonvulsant (78.1% seizure control rate), with adverse effects of sedation and intellectual depression. Seizure control was achieved in 77.1% of patients on a single drug as opposed to 55.6% on combination of phenytoin and phenobarbitone (p less than 0.05). The overall seizure control rate was 66%.
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PMID:Plasma level distribution, effect and toxicity of antiepileptic drugs among Ethiopian epileptics. 230 55

Phensuximide (PSX) is a 2-arylsuccinimide useful in the treatment of absence seizures. PSX is a mild urotoxicant and is structurally related to N-phenylsuccinimide (NPS) and its antifungal derivatives. Since substitution of the phenyl ring of NPS with chloro or tert-butyl groups can produce compounds with enhanced nephrotoxic potential, it was felt that similar substitutions on the phenyl ring of PSX also might produce derivatives with enhanced nephrotoxic potential. Three derivatives of PSX were prepared and tested: 2-(3-chlorophenyl)-N-methylsuccinimide (CPMS); 2-(4-tert-butylphenyl)-N-methylsuccinimide (BPMS) and 2-(3,5-dichlorophenyl)-N-methylsuccinimide (DPMS). In one set of experiments, male Fischer 344 rats were administered a single intraperitoneal (i.p.) injection of a succinimide (0.4 or 1.0 mmol kg-1) or vehicle (sesame oil, 2.5 ml kg-1) and renal function monitored at 24 and 48 h. Only minor changes in renal function were noted with the PSX derivatives. BPMS and DPMS (1.0 mmol kg-1) treatment induced mild renal tubular necrosis and thickening of the glomerular membranes. However, no significant morphological changes were noted in ureters, bladder or liver in any treatment group. In a second set of experiments, rats were pretreated with phenobarbital (75 mg kg-1 day-1, i.p., 3 days) followed by a single i.p. injection of DPMS (0.4 or 1.0 mmol kg-1) or DPMS vehicle. Renal function was monitored as before. Phenobarbital pretreatment did not markedly enhance the functional nephrotoxicity induced by DPMS (0.4 mmol), but tubular necrosis was greater than observed in non-phenobarbital-pretreated rats receiving DPMS (1.0 mmol kg-1). In addition, hepatotoxicity was observed as the appearance of numerous non-staining vacuoles in hypertrophied hepatocytes. In the phenobarbital plus DPMS (1.0 mmol kg-1) treatment group, all rats died by 48 h. Prior to death, rats exhibited increased proteinuria (+3), hematuria (+3) and blood urea nitrogen concentration. At 24 h, kidneys from rats treated with phenobarbital plus DPMS (1.0 mmol kg-1) exhibited extensive proximal tubular necrosis and numerous glomeruli with thickened membranes. Hepatotoxicity was more pronounced than with phenobarbital plus DPMS (0.4 mmol kg-1) at 48 h and urinary bladders had focal areas of erythrocytes pooling below the epithelial lining. These results demonstrate that although NPS and PSX are structural analogs, chemical substitutions that enhance the nephrotoxic potential of NPS do not have a similar effect on PSX. In addition, DPMS can induce urotoxicity in a manner similar to that observed for PSX and probably induces toxicity via one or more metabolites.
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PMID:Acute toxicity induced by 2-aryl-N-methylsuccinimides. 236 80

Phensuximide (PSX), methsuximide (MSX) and ethosuximide (ESX) are succinimide antiepileptic agents used worldwide in the treatment of absence seizures. A previous study from our laboratory demonstrated that PSX (0.3 or 0.6 mmol kg-1 day-1, i.p.) induced urotoxicity following daily administration for 5-7 days in Fischer 344 rats, but PSX (1.25 mmol kg-1, i.p.) induced only minimal urotoxicity following acute administration. The purpose of this study was to determine the acute nephrotoxic potential of MSX and ESX in male Fischer 344 rats and if antiepileptic succinimide-induced urotoxicity is potentiated by phenobarbital pretreatment. In one set of experiments, rats (four rats per group) were administered a single intraperitoneal (i.p.) injection of a succinimide (0.4 or 1.0 mmol kg-1) or vehicle (sesame oil, 2.5 ml kg-1), and the renal function was monitored at 24 and 48 h. Neither ESX or MSX induced substantial changes in renal function or morphology, which suggests that neither compound is acutely nephrotoxic. Similar results were obtained with PSX, which supported our earlier findings with this antiepileptic agent. In a second set of experiments, rats (four rats per group) were pretreated for 3 days with phenobarbital (75 mg kg-1 day-1, i.p.) prior to receiving a succinimide (0.4 or 1.0 mmol kg-1, i.p.) or vehicle (sesame oil, 2.5 ml kg-1, i.p.). Renal function was monitored at 24 and 48 h after the last injection. Phenobarbital pretreatment had only minor effects on ESX- or MSX-induced renal effects, with no significant morphological changes detected between treated and pair-fed control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute effects of the antiepileptic succinimides on the urinary tract and potentiation of phensuximide-induced urotoxicity by phenobarbital. 238 Apr 83

The effects of clinically used anticonvulsant drugs on high-frequency sustained repetitive firing (SRF) of action potentials and on postsynaptic responses to iontophoretically applied gamma-aminobutyric acid (GABA) have been compared to establish a classification of anticonvulsant drugs based on cellular mechanisms of action. By using concentrations in the range of therapeutic cerebrospinal fluid values in humans, drugs have been separated into three categories: Phenytoin, carbamazepine, and valproic acid limited SRF, but did not alter GABA responses. Phenobarbital, clonazepam, and diazepam augmented GABA responses and limited SRF only at concentrations above the therapeutic range in ambulatory patients but that are achieved in the acute treatment of status epilepticus. Ethosuximide failed to affect SRF or GABA responses even at supratherapeutic concentrations. Ability of an anticonvulsant to limit SRF correlated well with efficacy against generalized tonic-clonic seizures clinically and against maximal electroshock seizures in experimental animals. Augmentation of GABA responses and lack of limitation of SRF correlated with efficacy against generalized absence seizures in humans and against pentylenetetrazol-induced seizures in animals. However, ethosuximide must act against generalized absence seizures and against pentylenetetrazol-induced seizures by a third, as yet unknown, mechanism. Other actions occurring at supratherapeutic concentrations correlated with clinical toxicity.
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PMID:Anticonvulsant drug mechanisms of action. 240 25


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