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

Antiepileptic drug withdrawal must be considered in seizure-free patients. It is theoretically possible. A seizure relapse is frequent. Numerous factors predictive of relapse are known, but they are of limited value. A favorable outcome depends mainly on the patient's epileptic syndrome. Drug reduction must be carried out stepwise, with a slow dose-tapering. A partial withdrawal: reduction of polytherapy to monotherapy, or reduction in daily doses, can also be wise.
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PMID:[Stopping antiepileptic treatment]. 219 58

Sodium phenobarbitone (20 and 70 mg/kg) had a significant anticonvulsant action against pentylenetetrazole-induced seizures, which persisted for 21 days of treatment. On drug withdrawal there was a significant decrease in seizure threshold below control level 24-48 h after the last dose of 70 mg/kg. Phenytoin (40 mg/kg) had a significant anticonvulsant action after 7 days of treatment and this persisted for 21 days of treatment. On drug withdrawal there was a significant decrease in seizure threshold 48 h after the last dose. Lorazepam (0.1 mg/kg) had a significant anticonvulsant action, but the group tested after 21 days of treatment did not differ from the controls, indicating that tolerance had developed to this effect; on drug withdrawal there was a decrease in seizure threshold from 24 to 72 h. The only drug to increase aggressive behaviour was sodium phenobarbitone (70 mg/kg); this reached significance after 14 and 21 days of treatment and occurred 8 h after drug administration; 0.5 h after drug administration phenobarbitone (70 mg/kg) abolished aggressive behaviour. After 7 days of treatment phenobarbitone (70 mg/kg) increased social behaviour 0.5 h after administration and this was still increased after 21 days of treatment. On drug withdrawal, there were no changes in aggressive behaviour, but there were significant decreases in social behaviour 24 and 48 h after phenobarbitone (70 mg/kg) withdrawal and 24, 48 and 72 h after lorazepam (0.1 mg/kg) withdrawal.
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PMID:Changes in seizure threshold and aggression during chronic treatment with three anticonvulsants and on drug withdrawal. 230 12

Studies on discontinuing medication in epileptic patients who have been maintaining favorable progress and who have remained free of epileptic seizures for a long period have only been reported in comparatively small numbers and the conditions necessary to evaluate such patients as well as the methods used to enable the discontinuation of antiepileptic drug treatment to be decided have not yet been established. With the recent rapid advances in the treatment of epilepsy, any long-term treatment should be designed to include the possibility that the discontinuation of medication may be possible and this possibility should be understood from the start of treatment planning. In this study, the author has attempted to gradually or completely withdraw medication from epileptic patients who maintain favorable progress, using specific criteria and methods established by the author. The criteria used were: (1) patients should have been free of epileptic seizures for three years or more, (2) no epileptic discharge had appeared on the EEG within the previous 2-3 years (recorded during sleep as well as when awake) and (3) the patient's consent should have been obtained regarding the gradual or complete withdrawal of medication. The subjects were 40 patients (23 males and 17 females) with a mean age of 32.2 years. Seizures were primary generalized tonic/clonic in type (P-GTC) in 4 patients, complex partial seizures (CPS) in 22 and generalized sleep convulsions (GC(S)) in 14. In this study, patients with absence epilepsy taking a favorable course and those with benign childhood epilepsy showing epileptic discharges in the temporal to central region (rolandic seizure) or in the occipital region were not included. If epileptic discharges appeared on EEG recordings in the course of this study during the process of gradual drug withdrawal aiming toward complete drug withdrawal, attempts to completely withdraw medication were suspended. In this study, therefore, the period before the process in which the cessation of attempts at complete withdrawal of medication was involved due to the EEG showing epileptic discharges was taken as 'the former period' and the period in which the above process was involved was taken as 'the latter period'.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Discontinuation of antiepileptic drug treatment in controlled seizure patients]. 240 39

Amygdala-kindled rats were treated with valproic acid (VPA; administered as its sodium salt) 3 times daily at 200 mg/kg i.p. for 6 weeks, and anticonvulsant and adverse effects during this period were studied. Groups of nonkindled rats were treated in parallel for determination of VPA and its major active metabolites in various brain regions after different durations of treatment. After the first injection of VPA, 200 mg/kg, seizure severity, seizure duration and duration of electrical afterdischarges recorded from the stimulated amygdala were reduced significantly, but only one of nine animals was protected completely from kindled seizures. At day 3 of chronic treatment, the anticonvulsant activity of VPA had increased markedly so that seven of nine animals were totally protected from seizures. However, this potent anticonvulsant effect was only transitory so that after 1 week of treatment the anticonvulsant effect of the medication was similar to that obtained after the first dosing. The effect of VPA remained at this level for the subsequent weeks, but there was a second, more permanent increase in the number of protected animals after 4 to 6 weeks. Plasma and brain levels of VPA and its metabolites remained relatively constant throughout the chronic treatment although there was a moderate accumulation of some metabolites, e.g., trans isomer of 2-propyl-2-pentenoic acid, in specific brain nuclei. The most prominent adverse effects of VPA were ataxia, muscle relaxation, wet-dog shake behavior and an increase in body temperature. Except for body temperature, tolerance developed to these adverse effects, but escape from wet-dog shake behavior occurred much more rapidly than reduction of other adverse effects. Pathohistological examination of liver sections from animals treated with VPA for 6 weeks showed no indication of any hepatotoxic effects. After drug withdrawal, kindled seizure parameters returned toward control values without evidence of significant carry-over effects. Five days after termination of treatment, only minute amounts of VPA and trans isomer of 2-propyl-2-pentenoic acid were determined in some brain regions, indicating that there was no persistence of active drug or metabolite concentrations in the brain.
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PMID:Valproic acid in amygdala-kindled rats: alterations in anticonvulsant efficacy, adverse effects and drug and metabolite levels in various brain regions during chronic treatment. 250 34

Using information from a database of 5,000 cases of epilepsy, the author studies the clinical evolution of 3,601 patients who had been followed over a period between 1 and 40 years (mean follow-up period, 10 years). According to the results obtained with anticonvulsant drugs, controllable forms of epilepsy were those in which at least 1 years had transpired without seizures occurring. This accounted for 74.7% of the cases. Of the remaining 25.3%, 4.3% presented occasional seizures and 21% presented seizures that did not respond to medication, in particular 515 cases that could be considered severe or untreatable forms of epilepsy. Anticonvulsant medication was discontinued in 760 epileptics. Only 20% of these patients had relapses after a mean follow-up period of approximately 5 years. Risk factor determining the control of seizures or the possibility of successful drug withdrawal were as follows: time lapse before diagnosis, concurrence of different types of seizures in the same patient, presence of status, permanent neurological deficits as well as mental disorders. Permanent neurologic deficits would seem to be of greater importance than mental disorders in determining drug withdrawal.
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PMID:[Possibilities for recovery in epilepsy]. 262 38

Four criteria should be fulfilled when establishing an animal model of alcoholism. (1) The animal should voluntarily and selectively consume a solution of the drug to yield pharmacologically significant blood alcohol concentrations. When ethanol is consumed for several weeks under these conditions, (2) the animals should exhibit tolerance to the acute effects of the drug. Furthermore, (3) abrupt termination of drug administration should result in physical signs of drug withdrawal (e.g. audiogenic seizures). (4) Changes in endocrine and liver function would also be expected to occur following the chronic administration of alcohol, such effects being particularly pronounced if the diet of the animal is nutritionally deficient. A number of self-administration, operant conditioning and forced alcohol administration models are critically assessed. A detailed description of the models in which rodents are forced to consume increasing quantities of alcohol as part of a nutritionally enriched milk diet suggests that this method fulfils most of the above criteria.
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PMID:Rodent models of alcoholism: a review. 267 61

Female Sprague-Dawley rats were placed on a 6-week barbital feeding regimen, previously documented to result in drug tolerance and dependence. Groups of animals were sacrificed on the 2nd and 5th day of each week, up to week 5, or at various time points following drug withdrawal. Cerebellae and cerebral cortices were collected for cyclic GMP (cGMP) measurements. Initial suppressions of cGMP were seen in both the cerebellum and cerebral cortex during early weeks of the feeding regimen. These gradually returned essentially to control levels by the end of 5 weeks, a finding consistent with the development of tolerance to chronic barbiturates in the cGMP system. Barbital was withdrawn after 6 weeks of chronic administration. Four hours after withdrawal, a dramatic elevation of cerebellar cGMP was seen. This elevation was coincident with a significant decline in serum barbital levels and preceded the onset of weight loss, spontaneous seizures and locomotor depression. The elevation of cGMP was less dramatic but still apparent at 72 hr postwithdrawal when all other evaluated parameters had returned to control values. Alterations of cGMP during chronic barbital treatment and subsequent to abrupt barbital withdrawal may reflect aberrations in the function of neurotransmitter pathways involved in regulating cGMP in the cerebellum. Further, the elevation of cGMP after barbiturate withdrawal may itself play a functional role in the manifestation of barbital abstinence.
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PMID:Development of tolerance to chronic barbital treatment in the cerebellar cyclic guanosine monophosphate system and its response to subsequent barbital abstinence. 299 85

A retrospective survey on the frequency of seizure-recurrence after drug withdrawal in all forms of adolescent seizures has been undertaken to detect possible prognostic criteria. Patients were selected according to 3 criteria: first seizure between 11 and 19 years of age; out-patients seen by one of us between 1955 and 1979 within the year of onset of epilepsy; all patients followed for at least 5 years after the first seizure. Two-hundred and seventy two patients entered the study. One-hundred and four patients (49 per cent) relapsed, most of them (83 per cent) within the first year after drug withdrawal. In univariate analysis, partial seizures, a normal initial EEG, an isolated seizure, a short length of illness, a long seizure-free period, one seizure only during the first year were significantly linked to a low relapse rate. The probability of being seizure-free after drug withdrawal was about 73 per cent in partial epilepsy, 20 per cent in idiopathic generalized epilepsy, and 36 per cent in undetermined generalized epilepsy. In patients having had a single seizure a dramatic difference was noted according to the seizure type: 12 per cent of relapses after a partial seizure, 69 per cent after a generalized seizure. Neither the age of onset of epilepsy nor the presence of an etiological factor were significant variables in predicting the outcome. When all factors were analysed simultaneously with Cox's hazard function, the type of seizure and the initial EEG appeared to be the only two independent factors significant for a risk of relapse.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Discontinuation of treatment in epileptic seizures in adolescence]. 310 8

We compared the cognitive effects of carbamazepine and phenytoin with neuropsychological tests exploring intelligence, vigilance, attention, memory, and visuomotor performances in 25 epileptics (13 receiving carbamazepine and 12 receiving phenytoin) and 26 matched normal controls. Patients were seizure free for at least two years and taking prolonged monotherapy. We also evaluated the effects of drug withdrawal by retesting patients three months after reduction at half drug dose and three months and one year after complete withdrawal. Our findings suggest that phenytoin affects the cognitive functions more than carbamazepine does, although the negative effects of both drugs are reversible by complete therapy withdrawal.
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PMID:Carbamazepine and phenytoin. Comparison of cognitive effects in epileptic patients during monotherapy and withdrawal. 339 63

While 80% of patients who develop epilepsy will enter prolonged remissions with drug therapy, there is no agreement about who can safely be withdrawn from treatment without the risk of relapse. In light of the fact that seizure recurrence often has very important social implications, the final decision about drug withdrawal must be made by the patient and their family after full consultation with their physician about possible risks and benefits.
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PMID:Drug withdrawal and epilepsy. When and how? 339 68


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