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PubMed2001

[Febrile convulsions, Treatment and prognosis].

Epidemiological data indicate that the long-term prognosis in the vast majority of children with febrile seizures is good. Three main problems are important for the treatment: febrile seizures are extremely upsetting for the parents, the recurrence rate is 30-40% and the febrile status occurs unpredictably and is potentially damaging to the CNS. There is universal agreement that daily prophylaxis with valproate, primidone, or phenobarbital should only be used in highly selected cases, if at all. The effectiveness of phenytoin and carbamazepine has not been documented. Antipyretic treatment does not reduce the recurrence rate. Intermittent diazepam prophylaxis at times of fever may or may not reduce the recurrence rate significantly, but there is no data to suggest that it improves the long-term outcome, as compared with short-term seizure control, in terms of IQ, cognition, academic progress, motor control, and subsequent epilepsy. Acute anticonvulsive treatment with rectal diazepam in solution or other benzodiazepines is effective in aborting recurrent seizures with almost the effectiveness of i.v. treatment and is safe, simple, and easy to use for the parents. The long-term prognosis is probably uninfluenced by the type of treatment given in early childhood. It has not been established that acute anticonvulsive treatment with benzodiazepine is better than placebo.

Analgesics, Non-Narcotic↗
PubMed2002

[Evaluation of antiepileptic therapy during pregnancy].

OBJECTIVE: The aim of the study was to analyse the course of pregnancy and labour in women with epilepsy. MATERIAL AND METHODS: The study was carried out on 53 pregnant women with epilepsy who delivered in the Department of Obstetrics and Perinatology of the University School of Medicine in Lublin (group E). RESULTS: In the group of women with epilepsy there were observed more pregnancy complications. The mean birth weight of infants and the condition of the infant after birth evaluated were lower in the study group E according to Apgar score. The increased risk of congenital malformations and intrauterine foetal growth retardation were observed in children exposed to valproate or carbamazepine in monotherapy or combination of phenobarbital and phenytoin and the combination of phenobarbital, phenytoin and primidone in polytherapy. CONCLUSION: Women with epilepsy require appropriate pregnancy planning and appropriate neurologic and obstetric care preconceptionally and during pregnancy.

Adult↗
PubMed1976

Ultramicro gas-chromatographic analysis for anticonvulsants, with use of a nitrogen-selective detector.

We describe a procedure for determining phenobarbital, primidone, and diphenylhydantoin simultaneously in 50-mul volumes of serum by use of gas chromatography and a detector with heightened sensitivity and selectivity for nitrogenous compounds. The drugs, together with an internal standard, 5-allyl-5-phenyl barbituric acid, are extracted from serum by the procedure of MacGee [Anal. Chem. 42, 421 (1970)]. The drugs are converted to their methyl derivatives by a modification of the procedure of Greeley [Clin. Chem. 20, 192 (1974)] and then analyzed on a column containing 3% OV-1, with a temperature program, and detected by a nitrogen-selective detector. The method is reproducible to about 7%. Sensitivities of 0.5 mg/liter for 50-mul serum samples are attained routinely. Mephobarbital interferes with the analysis because methylation yields the same product as methylated phenobarbital. Total analysis time for a single sample is 15 min.

Chromatography, Gas↗
PubMed2006

[Rapid analysis of antiepileptic drugs in human plasma by micellar electrokinetic capillary chromatography].

AIM: To develop a rapid and feasible method based on micellar electrokinetic capillary chromatography (MECC) for the simultaneous determination of antiepileptic drugs (AEDs)--phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ), primidone (PRM) and clonazepam (CZP) in human plasma. METHODS: Several factors that impact the separation of AEDs with MECC were investigated, such as concentration of sodium dodecyl sulfate (SDS), buffer compositions, pH, organic modifier, internal diameter and temperature, and an optimized MECC running condition was obtained the running buffer consisted of 8 mmol x L(-1) phosphate, 3 mmol x L(-1) sodium tetraborate, and 50 mmol x L(-1) sodium dodecylsulfate (SDS) (pH 8.0), containing acetonitrile (ACN) (18%) as organic modifier. Detection at 210 nm, run at 25 kV at 30 degrees C in a untreated fused silica capillary (50/45.5 cm length, 50 microm ID). RESULTS: The reproducibility of both migration time and relative peak area with MECC analysis were appropriate for the intra- and inter-assay coefficients. The evaluated drugs concentration intervals of PRM 1.0-40.0 microg x mL(-1), PB 1.0-60.0 microg x mL(-1), PHT 1.0-40.0 microg x mL(-1), CBZ 1.0-40.0 microg x mL(-1), CZP 0.2-8.0 microg x mL(-1) were linear with correlation coefficients higher than 0.999 1, and coefficients of the variation of the points of the calibration curve lower than 10%. The recoveries of AEDs varied from 80.0% to 100.0%, depending on the drug, with coefficients of the variation lower than 10.0%. CONCLUSION: The MECC technique is showed to be rapid, simple, efficient and low cost when applied to monitoring therapeutic drugs in patient treated with a combination of PHT and other AEDs such as hepatic enzyme-inducing agents.

Anticonvulsants↗
PubMed1991

[Effectiveness of bromide in therapy resistant epilepsy of dogs].

In therapy lasting between 8 and 79 (means = 31) months 22 epileptic dogs had been unsuccessfully treated with phenobarbital and/or primidone. Both drugs had been administered in their maximum dosages. In an add-on therapy, these dogs were given potassium bromide at a rate of 17 to 58 mg/kg daily for a period of 7 to 61 (means = 21) months. We could quantitatively evaluate the seizure data from 19 of the dogs: four became free of seizures; seven showed a greater than 50% reduction in seizure frequency; in two dogs, the seizures were reduced by greater than 50% but the number of seizure-days by less than 50%; in the remaining six dogs the therapy was unsuccessful. We achieved the best therapeutic results in animals that suffered only grand mal seizures. Grand mal in addition to other types of seizures and tonic seizures were affected to a lesser extent if at all. At the beginning of the therapy we saw temporary side effects--weakness in the hind limbs and sedation; these were temporary and dependent on the dosage. Serum concentrations differed even with the same dosage among individual dogs. The therapeutic range of bromide serum concentration was from 0.7 to 2.0 mg/ml. Most of the animals tolerated concentrations up to 1.5 mg/ml quite well. To begin an add-on therapy with potassium bromide we would recommend a daily dose of 30 to 40 mg/kg. During treatment, the dose should be determined for each individual dog.

Animals↗
PubMed1990

[Clinical and experimental control of optimal therapy in epilepsy].

On the basis of a psychopathologically calibrated battery of tests, the effects of four drugs commonly prescribed for the alleviation of epilepsy (Valproinat, Carbamazepin, Diphenylhydantoin, and Primidon) were examined before and after optimisation of therapy. The positive psychotropic effect of Valproinat and Carbamazepin, and probably also of Diphenylhydantoin, consists in the acceleration of the psychic and motor rate and in the reduction of viscosity and perseveration.

Anticonvulsants↗
PubMed1978

The extraction of antiepileptic drugs. Model study on partition coefficients.

To compare the extraction behaviour of hexane, toluene, chloroform, 1,2-dichloroethane, diethylether, ethyl acetate and acetone towards phenobarbital, phenytoin, primidone and carbamazepine, partition coefficients of these drugs between the above solvents and water (saturated with ammonium sulphate when working with acetone) were measured at different pH-conditions. Acetone rendered the highest partition coefficients for all drugs. Ethyl acetate was second in the range, except for carbamazepine, which showed a specific affinity for the chlorinated hydrocarbons.

Anticonvulsants↗
PubMed1989

[Factors influencing the effectiveness of preventive treatment of febrile convulsions].

The influence of risk factors predisposing to recurrences was assessed in 103 children with febrile convulsions who were given prophylactic treatment with phenobarbitone, primidone or sodium valproate at adequate doses and whose compliance with treatment was monitored. There was a greater risk of recurrence among girls. Increasing risk was observed with decreasing age at which children suffered the first febrile convulsion. Neither a family history of epilepsy, failure of previous treatment, history of perinatal incidents, focal or prolonged febrile convulsions, recognition of neurological disease nor the number of previous febrile convulsions led to any significantly greater risk in these children. There was an increased tendency for recurrence with increasing interval between the first febrile convulsion and the start of prophylactic treatment.

Anticonvulsants↗
PubMed1986

Anticonvulsant drugs: mechanisms of action.

A variety of the anticonvulsant drugs, including carbamazepine, phenytoin, primidone, phenobarbital, clonazepam, valproic acid, and ethosuximide, are available for use in the treatment of patients with seizure disorders. These anticonvulsants vary in their efficacy against experimental seizures in animals and against seizures in humans. The mechanistic basis for this variability in anticonvulsant drug action remains uncertain, but numerous mechanisms of action have been proposed. We have used mouse neurons in primary dissociated cell culture to study the action of these anticonvulsant drugs on several aspects of membrane excitability and synaptic transmission. We have proposed that the anticonvulsant drugs can be classified according to their actions on sustained high frequency repetitive firing (SRF) of action potentials and on postsynaptic gamma-aminobutyric acid (GABA) responses. Phenytoin and carbamazepine were both effective against SRF but did not modify postsynaptic GABA responses at therapeutically relevant concentrations. Phenobarbital, benzodiazepines, and valproic acid modified both SRF and postsynaptic GABA responses. Ethosuximide had no effect on SRF or GABAergic mechanisms. Based on these results, we have proposed that blockade of SRF may underlie the action of phenytoin, carbamazepine, phenobarbital, valproic acid, and benzodiazepines against generalized tonic-clonic seizures in humans and maximal electroshock seizures in animals. Enhancement of GABAergic synaptic transmission may underlie efficacy of benzodiazepines and valproic-acid drugs against generalized absence seizures in humans and pentylenetetrazol-induced seizures in experimental animals. The mechanism of action of ethosuximide against generalized absence seizures in humans and pentylenetetrazol-induced seizures in experimental animals may be by a third, as yet unknown, mechanism.

Action Potentials↗
PubMed1986

[Prenatal growth of children of epileptic mothers].

In this study 67 children of 59 females with epilepsy and on anticonvulsants were investigated. Children of epileptic women on medication with Primidon are of lower weight and have smaller heads than children from epileptic mothers without medication and children from parents without epilepsy.

Anticonvulsants↗
PubMed1987

[Orthostatic tremor: clinical aspects, pathophysiology and therapy].

Orthostatic tremor is characterized by its isolated occurrence in leg and trunk muscles during standing with undisturbed sitting, lying and walking. In a female patient with this tremor syndrome the basic electrophysiological feature of muscle activity was a 16 Hz, highly synchronized tremor in all leg muscles and sometimes in the arm muscles. This rhythmic EMG activity however, was not restricted to stance but occurred during all kinds of muscle activation in sitting, lying or standing positions, despite only standing was accompanied by a subjective sensation of unsteadiness and falling to the ground. Mechanical tremor analysis at the patella revealed an additional 8 Hz tremor caused by alternating large and small amplitudes of the 16 Hz tremor bursts. The occurrence of the 8 Hz tremor was much more related to the feeling of unsteadiness than the 16 Hz tremor. Single motor units mostly fired at a frequency of 8 Hz, but only at the time of tremor bursts. Hence the 16 Hz-pattern may not be explained as the result of a pure motoneuronal abnormality. There were no indications for abnormal reflexes contributing to tremor genesis. A fixed time relation of the tremor bursts in different muscles has been found suggesting a common generator within the CNS for the tremor. After successfully treatment with Primidon the pattern of muscle activation was normalized during sitting and lying, however, during standing and walking the 16 Hz tremor was still present. We believe that an unknown central oscillator is causing the tremor and central structures which are involved in stance regulation have a predominant access to switch on this oscillator.

Diagnosis, Differential↗
PubMed1988

Aspects of compliance: taking drugs and keeping clinic appointments.

Treatment of epilepsy depends on adherence to a drug regimen as prescribed and periodic assessment of progress. Typical problems of compliance to medication and adherence to follow-up in long-term epilepsy treatment in a clinical trial were analyzed. Zero drug levels, subtherapeutic levels, variable levels and delayed dose were measures of non-compliance to the drug regimen. Missed visits and non-drug-related dropouts from the study marked non-adherence. Data from 622 patients participating in a multicenter evaluation of the efficacy and toxicity of carbamazepine, phenobarbital, phenytoin and primidone, showed generally good compliance. Only 5% of patients had zero drug levels or greater than or equal to 24 h since prior dose at 2 or more visits. Good adherence to the protocol was demonstrated by 93% attendance as scheduled. The support structure of the study and the availability of a study assistant helped many patients to prevent potential problems and convert patients into excellent adherers.

Adolescent↗
PubMed1988

Relevance of poor compliance for seizure control.

The relationship of poor compliance to seizure control was analyzed in 101 patients with self-reported poor compliance in 2 seizure clinics. There was a close correlation of poor compliance and the coefficient of variation for phenytoin (P = 0.001), primidone (P = 0.01) and carbamazepine (P = 0.01). In comparison with self-reported compliers no difference was noted in seizure control and other clinical variables. Patients who experienced an increase of several seizures in temporal relationship with poor compliance more often reported loss of sleep (P = 0.006) and more often had frequent (more than 5 per year) seizures (P = 0.001) than non-compliers with a single seizure relapse or no change in seizure control. Exacerbation of seizures through poor compliance occurs primarily in patients with frequent seizures and through loss of sleep.

Adolescent↗
PubMed1978

Long-term use of the major anticonvulsant drugs.

The specific type of epilepsy must be identified. The history and the EEG provide the evidence. Drug selection is then based on the classification of the patient's epilepsy. Major drugs used in the management of epilepsy are phenytoin, phenobarbital, primidone, carbamazepine, ethosuximide and valproic acid. The physician should know their kinetics, interactions and side effects, and the value of monitoring blood levels of these anticonvulsant agents.

Abnormalities, Drug-Induced↗
PubMed1977

[Changes in the thyroid hormone system with combined anticonvulsion treatment of epileptic children and adolescents (author's transl)].

Anticovulsant combined treatment produces statistically significant reduction of total thyroxine, free thyroxine and protein-bound iodine. Total cholesterin is significantly raised on average of the total. Basal concentration of thyreotropic hormone is slightly lowered. The extent of changes is rather greater than with Valproat-, Diphenylhydantoin- and primidon permanent treatment; it corresponds with that seen in long term Carbamazepin treatment. No definite combinations of anticonvulsants could be found which would act in a particularly unfavorable fashion on the thyroid hormone system. In double combinations the changes in serum concentrations were the same as in triple combinations. The action of combined treatment in permanent treatment with single drugs is thought to be due to a removal of T4 from the transport protein link and induction of liver enzyme, which produces rapid conversion and metabolizing of T4. A hypothalamic action of combined antoconvulsants is discussed.

Adolescent↗
PubMed1983

Active metabolites in antiepileptic therapy. Reflections on a pharmacological joker.

Treatment with drugs that produce active metabolites in the organism may sometimes resemble playing cards that includes a joker. Both kinetically and dynamically the metabolites may be different from their parent compound, and antiepileptic drugs are no exception. Primidone, carbamazepine and valproate all have active metabolites, and the various problems which these mean for the treatment of epileptic patients are briefly discussed. Models for studying a parent compound and its active metabolite parallelly in man have been proposed for diazepam. These and other may be applied to antiepileptic drugs in order to increase the quality of their clinical use and the development of new drugs.

Anticonvulsants↗
PubMedDate not supplied

[Comparative study of the levels of anticonvulsants and their free fractions in venous blood, saliva and capillary blood in man].

There is a good correlation for the six anticonvulsants studied in mono and polytherapy in human serous and capillary blood. Blood can be taken either at the vein, or at the finger. The ratio free fraction and saliva/serous blood has given for phenobarbital 0.65 (0.52 - 0.83) and 0.30 (0.21 - 0.46), pH 5.9 - 7.5, phenytoin 0.11 (0.10 - 0.11) and 0.12 (0.08 - 0.23), primidone 0.81 (0.74 - 0.83) and 1.03 (0.88 - 1.11), carbamazepine 0.22 (0.20 - 0.26) and 0.37 (0.30 - 0.50), ethosuximide 0.99 (0.81 - 7.01) and 0.95 (0.90 - 1.30), and less than 0.10 for valproate levels. In certain conditions, saliva may have a considerable place in drug monitoring.

Anticonvulsants↗
PubMed1984

Excretion of organic acids associated with biotin deficiency in chronic anticonvulsant therapy.

Urinary organic acids, known to be elevated in children with biotin deficiency, were determined in 7 epileptics under long-term therapy with anticonvulsants and in three controls. Four patients administered phenytoin, primidone, phenobarbital, or carbamazepine, alone or in combination, had reduced plasma biotin levels (less than 250 ng/l) and an elevated excretion of certain organic acids indicating a possibly decreased activity of propionyl CoA carboxylase (3-OH-propionate, methylcitrate) and 3-methylcrotonyl CoA carboxylase (3-methylcrotonate and the glycine conjugate, 3-OH-isovalerate). Two epileptics receiving sodium valproate alone had normal circulating biotin levels and no changes in level of the investigated urinary acids were found. These findings indicate that the reduced biotin levels seen in epileptics receiving other anticonvulsants than sodium valproate lead to an elevated excretion of certain organic acids in urine.

Adult↗