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

During the past 10 years, better results in the treatment of epilepsy have been obtained through the application of pharmacokinetic data to drug therapy of epilepsy. However, pediatric drug therapy is complicated by the continuous change in body weight and body composition with the growth and development, especially during infancy. Younger children require a higher dose per kilogram of body weight than older children in order to achieve comparable plasma concentrations. Plasma levels and seizure control were investigated in a prospective randomized study when phenytoin, carbamazepine (CBZ) or sodium valproate (VPA) was given as a single drug to pediatric patients with several types of epileptic seizures. Studies on newly referred, previously untreated children suggest that both partial and generalized tonic-clonic seizures can be prevented by each of the three drugs. No significant differences in clinical efficacy were found among the three drugs, when optimum plasma concentration ranges were maintained with blood level monitoring. Clonazepam (CZP) may be effective in partial seizures. However, as a wide range of plasma levels was associated with complete freedom from seizures, it was not possible to define a therapeutic range for CZP. Any patient who receives multiple-drug therapy is at risk to develop a drug-drug interaction. Simultaneous administration of VPA was associated with a raised plasma level of carbamazepine-10,11-epoxide (CBZ-E), a major metabolite of CBZ, relative to the CBZ dose, whereas the plasma CBZ level remained unaltered. High plasma concentration of CBZ-E may be responsible for side effects in some patients. Drug-protein binding interactions are another source of side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Aspects of antiepileptic drug therapy in children]. 210 92

The anticonvulsant effects of two doses of clonazepam (CZP, Rivotril Roche, 0.1 and 1 mg/kg i.p.) were studied on model motor seizures induced by strychnine, bicuculline, 3-mercaptopropionic acid and metrazol in male laboratory rats (Wistar strain). In the first part the effects of different doses of the convulsants were investigated and for interaction with CZP doses were chosen after which more than 70% of the animals displayed generalized tonic-clonic convulsions (a grand mal seizure). Strychnine induced this type of seizure only: two doses (2 and 3 mg/kg s.c.) were used. CZP reduced the incidence of convulsions only after the larger dose, but plain solvent (propylene glycol, ethanol, water) was equally effective. The other substances first induced a seizure of minimal (mainly clonic) convulsions and only later a grand mal seizure. CZP was highly effective against bicuculline (3 mg/kg s.c.) and metrazol (100 mg/kg s.c.), but was less so against 3-mercaptopropionic acid. The effect on grand mal seizures was more pronounced in every case than on minimal seizures. The decisive role in the anticonvulsant effect of CZP is played by the mechanisms by which the convulsants induce epileptic manifestations. CZP is most effective against substances acting on the supramolecular complex GABA receptor (benzodiazepine receptor) chloride ionophore (bicuculline and probably metrazol).
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PMID:Anticonvulsant effects of clonazepam on chemically induced convulsions. 215 Sep 91

A rapid kindling procedure was used to distinguish between the anticonvulsant activity of drugs and their ability to retard the kindling process. MK-801 is a specific ligand at the phencyclidine (PCP) recognition site, and acts as a noncompetitive antagonist of NMDA-type glutamate/aspartate receptors. Intraperitoneal injections of MK-801 (0.5-4.0 mg/kg IP) significantly reduced the cumulated effect of 12 2-hr kindling stimulations, as determined from behavioral measures of seizure activity in immediately ensuing 24-hr drug-free kindling sessions; however, the corresponding electrographic effects did not reach significance. MK-801 also showed significant anticonvulsant activity when injected in fully kindled rats. Higher doses tested were accompanied by locomotor and postural effects. The anticonvulsant benzodiazepine, clonazepam, formulated with a proprietary diluent (as Rivotril, Roche), injected in anticonvulsant doses during the first 12 kindling sessions (0.64 mg/kg IP, repeated after 9 hr) did not significantly affect the course of subsequent sessions of drug-free kindling. Systemic injections of kynurenic acid (300-600 mg/kg IP 4 hours), a nonspecific antagonist of glutamate receptors in vitro, were without significant anticonvulsant or antikindling activity. Activity of NMDA-sensitive glutamate/aspartate receptors associated with the PCP recognition site may induce lasting facilitation of neural transmission; this facilitation may be responsible for the remote propagation and progressive enhancement of seizure activity kindled in the amygdala. The facilitatory process appears to be antagonised by MK-801.
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PMID:The effect of the NMDA receptor antagonist, MK-801, on the course and outcome of kindling. 216 Nov 8

Although reliable biological markers of dysfunctional childhood anxiety disorders are lacking, such disorders can be recognized by their symptoms. In separation anxiety and avoidance disorders, anxiety is limited to certain settings; in overanxious disorder, anxiety is generalized. Treatment for childhood anxiety disorders has included behavioral and pharmacologic intervention alone or in combination, but evidence of the efficacy of medical treatment is sparse. Some antidepressants and benzodiazepines have undergone limited studies. Clonazepam has been chosen for further study because in adults it reduced panic attacks and produced few serious side effects. In extensive studies of clonazepam for childhood seizure disorders, side effects were reported, but later reports indicate that many side effects were due to rapid induction and large doses. Transient drowsiness, lethargy, irritability, or excitability have been reported in various epilepsy studies. Clonazepam's minimal potential for drug interactions is another feature recommending it for extended trials in childhood anxiety disorders, and such a double-blind crossover study is underway.
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PMID:High anxiety in children. 218 21

Because hypothermia and anorexia were previously found to be more sensitive indices of the effects of lindane than were convulsions, these endpoints were used to quantify the ability of benzodiazepines (BDs) and phenytoin either to ameliorate or exacerbate the toxicity of lindane in the rat. After administration of lindane (40 or 50 mg/kg) in oil per os, toxicity was counteracted by phenytoin and the "central" BD agonists diazepam and clonazepam, but was worsened by Ro 5-4864 a "peripheral" BD agonist. Clonazepam and diazepam were each more effective in counteracting lindane-induced anorexia than in stimulating food intake, presumably because the animals had been fasted and probably even controls ate maximally when food was presented. Diazepam alone (3 injections in 1 day) produced withdrawal-induced decreased food intake the following day. Clonazepam and diazepam alone each transiently decreased colonic temperature, yet effectively blocked the more severe hypothermia produced by lindane. Ro 5-4864 by itself did not produce any measurable effects, yet exacerbated all of the effects, including lethal effects, of lindane. The present findings are compatible with other evidence that lindane and Ro 5-4864 act at the picrotoxinin receptor of the GABAA-activated chloride channel and that systemic administration of agents acting at this site may produce a constellation of effects, including seizures, hypothermia and anorexia.
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PMID:"Central" and "peripheral" benzodiazepines and kinetics of lindane-induced toxicity. 247 Dec 14

Convulsions from abrupt clonazepam withdrawal in patients with a seizure history or concurrent neuroleptic use have been described in the literature. This is a report of a patient without these precipitating factors developing seizure despite "gradual" reduction of clonazepam by .5 mg every 4 days. The possibility of clonazepam withdrawal seizures should be kept in mind even in patients not considered at risk for developing seizures. Clonazepam cessation should be more gradual, even slower than .5 mg every 4 days.
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PMID:Seizure in gradual clonazepam withdrawal. 232 91

The Lennox-Gastaut Syndrome is one of the most refractory form of epilepsy and a variety of compounds, such as traditional antiepileptics, "new anticonvulsants" and non-anticonvulsant drugs has been tested. ACTH and, among the traditional antiepileptics. Clonazepam and Sodium Valproate showed the most favorable effects. The immediate (within 6 months) therapeutic response to ACTH and Clonazepam is satisfactory, with a more than 50% reduction of seizures in about one half of patients; after one year, however, only a small percentage of cases (7-10%), rather close to that with spontaneous remission, shows some therapeutic benefit. Valproate, when used as a single drug, produces a decrease in seizures (greater than 50%) in 25-30% of pts. A list of compounds, such as amphetamine, taurine, amantadine, allopurinol and, among the new putative antiepileptics, cinromide and gamma-vinyl-GABA, has been tested with some occasionally observed improvement in seizure control. None of these compounds, however, is of really proven efficacy. An acquired general rule of treatment is to avoid complex polypharmacy and overdose; there is in fact good evidence that making the child drowsy will greatly increase the number of fits.
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PMID:[Lennox-Gestaut syndrome: therapeutic aspects]. 270 Aug 41

Clonazepam (1 mg h.s.) and temazepam (30 mg h.s.) were studied in 10 patients diagnosed as having insomnia with nocturnal myoclonus. Each subject underwent two nocturnal polysomnographic recordings while drug-free, two during treatment with clonazepam, and two during treatment with temazepam. Treatment sessions were 7 days long, and recordings were done on nights 6 and 7 of the treatment sessions. A 14-day washout period separated the treatment sessions. The order of drugs used in the first and second treatment sessions was randomized. Objective and subjective sleep laboratory data showed that both drugs improved the sleep of patients with insomnia in association with nocturnal myoclonus. Neither drug significantly reduced the number of nocturnal myoclonic events. Sleep changes were consistent with those produced by sedative benzodiazepines in general. Thus, the data support clinical reports that clonazepam, a benzodiazepine marketed for the indication of seizure, is useful in improving sleep disturbances associated with nocturnal myoclonus. Temazepam, a benzodiazepine marketed for the indication of insomnia, was found to be a suitable alternative to clonazepam in the treatment of insomnia associated with nocturnal myoclonus. The present data and other studies suggest the need for a model that explains why leg movements and sleep disturbances may wax and wane independently.
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PMID:Nocturnal myoclonus: treatment efficacy of clonazepam and temazepam. 287 85

Studies suggest that the 1,5-benzodiazepine clobazam possesses a favorable anticonvulsant profile due to its minimal neurotoxicity. The anticonvulsant and motor impairment effects of clobazam and 2 1,4-benzodiazepine, diazepam and clonazepam, were compared by dose-response analysis in amygdala-kindled rats and on 3 tests of motor function: gross motor impairment, a vertical screen test, and muscle tone. All drugs produced a significant, dose-dependent decrease in the duration of both behavioral and electrographic kindled seizure measures. Forelimb clonus suppression was the most sensitive measure of anticonvulsant drug effect. The order of potency for all effects was clonazepam greater than diazepam greater than clobazam. ED50s for the benzodiazepines' effects on motor impairment were compared to their ability to protect rats from forelimb clonus. Different spectrums of action for the various benzodiazepines were found depending on the comparison measure. Clonazepam had the most favorable ratio of potency for anticonvulsant vs. motor impairment activity when ataxia rating was the comparison measure. Diazepam had the most advantageous profile when the more sensitive screen test was used for comparison. Clobazam was not found to have a superior spectrum of action when compared across these measures. The results emphasize the importance of dose-response analyses and the consideration of behavioral measures used to assess beneficial and adverse effects of anticonvulsants.
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PMID:A comparison of the anticonvulsant effects of 1,4- and 1,5-benzodiazepines in the amygdala-kindled rat and their effects on motor function. 291 46

The article deals with a rare case of granulocytopenia following a seizure prophylaxis after a severe head injury. Although fatal complications like the one described occur extremely seldom, we want to emphasize the necessity of regular controls during the critical time period between the 10th and the 67th day of diphenylhydantoin treatment. The blood level should not exceed 10-20 micrograms/ml to prevent any toxic reaction to the myelopoetic system. If this treatment cannot be provided, we suggest to administer Clonazepam or Convulex.
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PMID:Diphenylhydantoin induced granulocytopenia following a seizure prophylaxis after a depressed skull fracture. 310 93


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