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At least 397 records · Page 22Linked to original sources
PubMed1983

Neonatal outcome in infants of epileptic mothers.

The effect of epilepsy and anti-epileptic treatment on neonatal outcome was investigated in 86 pregnancies terminating in delivery. Various maternal and neonatal parameters were considered. Each infant born to an epileptic mother was double-matched with two infants born to healthy mothers and the results were submitted for statistical analysis. Infants of epileptic mothers had smaller head circumference. Primidone was the only anti-epileptic drug, taken during pregnancy, to have a significant effect on infant head circumference. The results suggest that a drug effect, rather than an association with maternal epilepsy, is responsible for this difference. Hypertelorism is the only congenital anomaly to be significantly more frequent in newborns of epileptics. All drugs, except for primidone, were associated significantly with this anomaly. Further similar studies and prolonged follow-up of the infants of epileptic mothers are necessary before drawing any final conclusions regarding the outcome of these infants.

Analysis of Variance↗
PubMed1996

An acardiac acephalic monster following in-utero anti-epileptic drug exposure.

Acardia, the absence of the heart, is one of the rarest medical anomalies. The exact mechanism which causes this anomaly is still unknown. The authors report the acardiac acephalic fetus of an epileptic mother who was on primidone therapy. The mother who received no antenatal care stopped taking primidone (her sole medication) in the third month of pregnancy with the fear of delivering a malformed baby and had three convulsions until delivery. This is the first reported case of acardia associated with anti-epileptic medication. The cause of the anomaly in this patient may be an unknown genetic defect, the maternal epileptic disorder, the convulsions, the anti-epileptic medication, or a combination of these factors.

Abnormalities, Multiple↗
PubMed1994

An automated analytical method for the determination of felbamate in human plasma by robotic sample preparation and reversed-phase high performance liquid chromatography.

An automated analytical method for the determination of felbamate in human plasma is described. Sample cleanup and preparation was performed by means of a Zymate II laboratory robot and consisted of a liquid-liquid extraction of felbamate and the internal standard, primidone, from human plasma to dichloromethane. The dichloromethane was evaporated and reconstituted in a phosphate buffer. Separation was performed by reversed-phase high performance liquid chromatography using a 5 microns Hypersil ODS column (150 x 4.6 mm) and a mobile phase consisting of a mixture of phosphate buffer (pH = 6.5, 0.015 M) and acetonitrile (79:21, v/v). Quantitation was performed by measurement of the UV absorbance at a wavelength of 210 nm. The lower limit of quantitation was 0.100 micrograms ml-1 using 200 microliters of plasma. The mean absolute analytical recovery of felbamate was 75.2% (n = 28). The recovery of the internal standard, primidone was 74.7% (n = 10). The within-day precision was below 3.8% at all concentration levels, except at the lower limit of quantitation (18.3%). The within-day accuracy varied between -3.7 and +7.4%. The between-day precision was below 5.0% at all concentration levels. The between-day accuracy of the method varied between -5.7 and +1.6%. The selectivity of the method towards several other anti-epileptic drugs has been demonstrated.

Anticonvulsants↗
PubMed1977

Simultaneous determination of anticonvulsant drugs by gas-liquid chromatography.

A quantitative gas-liquid chromatographic method for the determination of blood levels of ethosuximide, phenobarbitone, primidone and diphenylhydantoin is described. All four compounds are determined using 1 ml of serum. A simple, direct extraction technique is employed. Ethosuximide is analysed without derivatization. Subsequent flash alkylation with trimethylanilinium hydroxide allows the simultaneous determination of phenobarbitone, primidone, and diphenylhydantoin.

Anticonvulsants↗
PubMed2000

Seizure-inducing paradoxical reaction to antiepileptic drugs.

We report on an 18-month-old girl with a seizure frequency of five/day, receiving an antiepileptic polytherapy consisting of primidone, clonazepam and phenytoin. Following discontinuation of clonazepam and primidone, the patient has been seizure-free under monotherapy for 2 years and shows marked developmental progress. Possible mechanisms of this paradoxical effect of antiepileptic drugs and the implications for antiepileptic therapy are discussed.

Anticonvulsants↗
PubMed2002

Unverricht-Lundborg disease with cystatin B gene abnormalities.

The clinical, neurophysiologic, and genetic findings in two Japanese patients with the Unverricht-Lundborg type of progressive myoclonus epilepsy are described. The cystatin B gene of Patient 1 exhibited expansion of the dodecamer (12-mer) repeat located in the 5' region and a point mutation (G-->A mutation) in exon 2. The cystatin B gene of Patient 2 exhibited homozygous expansion of the dodecamer repeat. Both parents of Patient 2 were heterozygous carriers. The two patients had a similar clinical course, and their symptoms were similar to those of previously reported patients in Finland. They both had a good response to zonisamide and low-dose primidone. We recommend that zonisamide and low-dose primidone should be introduced as the first drugs of choice for the treatment of patients with the Unverricht-Lundborg type of progressive myoclonus epilepsy.

Adolescent↗
PubMed1985

Differential effect of anionic and cationic drugs on the synaptosome-associated acetylcholinesterase activity of dog brain.

The evoked effects of the negatively charged drugs phenobarbital and barbituric acid, the positively charged imipramine, perphenazine and trifluoperazine, and the neutral primidone, on the synaptosome-associated acetylcholinesterase activity were studied. A marked increase in the enzyme activity was exhibited in the presence of low concentrations (up to 3 mM) of phenobarbital, barbituric acid and primidone. Higher concentrations (up to 10 mM), however, led to a progressive inhibition of the enzyme activity. However, the activity of the enzyme was not affected by imipramine, but it was decreased by perphenazine and trifluoperazine. Arrhenius plots of acetylcholinesterase activity exhibited a break point at 23.4 degrees C for the untreated (control) synaptosomes, which was shifted to around 16 degrees C in the synaptosomes treated with the charged drugs. The allosteric inhibition by F- of acetylcholinesterase was studied in control synaptosomes and in those treated with the charged drugs. Changes in the Hill coefficients in combination with changes in Arrhenius activation energy produced by the charged drugs would be expected if it is assumed that charged drugs 'fluidize' the synaptosomal plasma membranes.

Acetylcholinesterase↗
PubMedDate not supplied

[How effective is the treatment schedule in children with infantile spasms?].

A fatal incident during combined anticonvulsive therapy with ACTH and Dexamethason prompted us to reevaluate our treatment results in 19 children suffering from infantile spasms. We followed Doose's recommendation using Clonazepam as a means of first choice. Failing that, than Dexamethason and Primidone was used. A combination of ACTH, Dexamethason and Primidone was administered to patients failing both treatment courses. Our results question the necessity, the tolerance limit and the efficacy of this treatment schedule. Therefore we propose a prospective multicentric study to reinvestigate the therapeutic guideliness for infantile spasms.

Adrenocorticotropic Hormone↗
PubMed1979

High pressure liquid chromatography for simultaneous analysis of anticonvulsants: comparison with EMIT system.

We present a new high pressure liquid chromatography (HPLC) method for the simultaneous analysis of primidone, phenobarbital, phenytoin, and carbamazepine in serum. The chromatographic separation is carried out using an Altex model 110-A pump, a 250 times 4.6 mm column containing 5 mum Spherisorb ODS particles and a variable wavelength ultraviolet detector set at 197 nm. The mobile phase is a mixture of acetonitrile, distilled water, and 1.75 M phosphoric acid (27:72.8:0.2). The flow rate is 1.5 ml/min, and the analysis time is 17 min. A 200 mul aliquot of serum is buffered at pH 5 and extracted with dichloromethane. The extract is evaporated to dryness and dissolved in methanol for chromatographic analysis. Cyclopal is used as the internal standard and quantification is achieved using peak height ratios. This HPLC method is evaluated for precision and accuracy with reference to the EMIT system. The least-squares regression analysis of comparison data for the drugs shows a favorable correlation. Also, a paired t-test indicates no significant difference for the HPLC and EMIT values for primidone, phenobarbital, phenytoin, and carbamazepine. From this study we conclude that this HPLC method could be successfully used for the simultaneous therapeutic monitoring of the four anticonvulsants.

Anticonvulsants↗
PubMed1984

The place of saliva in antiepileptic drug monitoring.

It has previously been shown that saliva phenytoin concentration bears a constant relationship to plasma free concentration whether protein binding of phenytoin is normal or disturbed by other drugs, pregnancy, renal failure, or hypoalbuminaemia. The present work examines the relationship between saliva (S), plasma free (F), and plasma total (P) concentrations of other anticonvulsants in 100 epileptic patients. Mean S/P ratios were for phenobarbitone 0.37 (r = 0.95), primidone 0.95 (r = 0.87), and carbamazepine 0.27 (r = 0.94). A highly significant correlation of S with F was found for these drugs, more significant than the correlation of S with P for carbamazepine in patients receiving multiple anticonvulsant drugs. Saliva valproate, however, had no predictive value for P or F. No binding to saliva proteins was demonstrated for any drug. Data for in vitro binding to plasma proteins was in good agreement with ex vivo data. Saliva is therefore a valid medium for monitoring treatment with phenobarbitone, primidone, and carbamazepine, as well as phenytoin.

Adolescent↗
PubMed1986

Carbamazepine drug interactions.

Carbamazepine (CBZ) is commonly prescribed as an anticonvulsant or for the pain of trigeminal neuralgia. The potential for clinically important drug interactions exists because CBZ may induce the hepatic metabolism of other drugs or, conversely, other drugs may induce or inhibit the metabolism of CBZ. Studies and case reports demonstrate that CBZ may accelerate the metabolism of phenytoin, phenobarbital (PB), primidone, valproic acid, and warfarin. Likewise, phenytoin, PB, and primidone may increase the hepatic metabolism of CBZ. Inhibition of the metabolism of CBZ has been caused by triacetyloleandomycin, erythromycin, propoxyphene, isoniazid, and cimetidine. Future investigations will document the clinical significance of the CBZ interactions as well as reveal new interactions.

Carbamazepine↗
PubMed1990

Clearance of phenylethylmalonamide during haemodialysis of a patient with renal failure.

Information is presented for the serum concentrations during haemodialysis of primidone, phenobarbitone, and phenylethylmalonamide (PEMA) in a patient with renal failure receiving chronic primidone therapy. The concentrations of drug and metabolites fell during haemodialysis, but PEMA concentrations were above normal at all times. The average renal clearance of PEMA during 6 h of dialysis was found to be 84.7 +/- 4.6 ml min-1.

Humans↗
PubMed1975

Efficacy of standard anticonvulsants in monkey model with spontaneous motor seizures.

Monkeys were rendered chronically epileptic by injection of alumina gel into the pre- and postcentral gyrus. To test the validity of this primate model, the effects of diphenylhydantoin (DPH), phenobarbital, and primidone on spontaneous seizures evaluated for 8 months with a Latin-Squar experimental design. All three drugs were effective, the frequency of seizures being reduced by at least one-half during 6 weeks with treatment as compared with 6 weeks without. In most monkeys the frequency and severity of seizures were correlated to the number of interictal spikes in the EEG, and were inversely related to the level of drug in plasma. During withdrawal of phenobarbital and primidone, epileptic activity increased over that during control periods. Side effects were minimal with all three drugs. Patterns of behavior, although they differed from one monkey to the next, exhibited trends specific to each drug but particularly DPH. The seizures of some animals seemed to be related to the sleep-waking cycle.

Aluminum↗
PubMed1985

Effects of pregnancy on antiepileptic drug utilization.

Pregnancy is associated with characteristic changes in the disposition of antiepileptic drugs; recent findings on this aspect of drug utilization are presented. In one study involving 48 pregnancies, the mean level-dose ratio of phenytoin decreased by 34%. In another study of 111 patients, phenytoin clearance increased gradually over the first 32 weeks of pregnancy and reached twice the preconception value. In two studies with phenobarbital, levels tended to decrease, although this effect was less pronounced than for phenytoin. Similarly for primidone, pregnancy had little effect on steady-state levels; however, levels of phenobarbital formed from primidone exhibited large decreases during pregnancy followed by increases after delivery. This effect was quite consistent. Carbamazepine clearance tended to increase to a relatively small extent. Limited data indicate that valproate levels decrease by 30 to 40% during pregnancy. The mechanisms responsible for these effects have not been elucidated and possibly include decreased bioavailability or compliance, increased metabolic clearance, or decreased plasma protein binding. Since the patient at risk of an increase in seizure frequency cannot be identified prior to conception, therapeutic monitoring is imperative during and after pregnancy.

Anticonvulsants↗
PubMed1983

Pharmacokinetics of antiepileptic drugs.

The rational use of antiepileptic drugs requires the consideration of their pharmacokinetics, which may be influenced by the physiological and pathological factors. Pharmacokinetic interactions between antiepileptic drugs may lead to considerable fluctuation in plasma drug concentration, and monotherapy is often preferable. The absorption of phenytoin depends on pharmaceutical formulation. Phenytoin is highly bound to plasma proteins, thus the changes in the unbound fraction are of clinical significance. The saturation kinetics of its metabolism and drug interactions have further consequences. Carbamazepine is well absorbed and largely metabolized. Due to the autoinduction its half-life shortens in chronic administration. Valproate is highly, but variably bound to plasma proteins. It is eliminated mainly by metabolism. Due to the long half-life of phenobarbital its plasma concentrations change slowly, and time to the steady-state may be up to 30 days, if no loading dose is given. Primidone is partly metabolized to phenobarbital, and at steady-state plasma concentration of phenobarbital often exceeds that of primidone. Diazepam, clonazepam and nitrazepam are largely bound to plasma proteins and extensively metabolized with the half-lives of 20 to 60 hours.

Adult↗
PubMed1982

Two antiepileptic drugs for intractable epilepsy with complex-partial seizures.

The value of adding a second antiepileptic drug in intractable epilepsy with complex-partial seizures was studied in a long-term prospective trial in 30 adult patients who failed to respond to the maximum use of carbamazepine, phenytoin, phenobarbital or primidone as the first drug. Based on the individual previous history of one-drug treatment, the most promising antiepileptic drug (carbamazepine, clobazam, clonazepam, phenobarbital, phenytoin, primidone, valproic acid) was added, if necessary until clinical toxicity occurred. A reduction of the seizure frequency by more than 75% was seen in only four patients (13%) exposed to a second drug in the event of failure of optimum one-drug treatment. The remaining majority of patients (87%) did not benefit from the second drug; in three patients the seizure frequency increased by more than 100%. The common practice of adding another drug in difficult-to-treat cases may need to be reconsidered until further evidence is presented that two drugs are more beneficial than one drug in the treatment of intractable epilepsy.

Anticonvulsants↗
PubMed2005

Genetic essential tremor in gamma-aminobutyric acidA receptor alpha1 subunit knockout mice.

Essential tremor is the most common movement disorder and has an unknown etiology. Here we report that gamma-aminobutyric acidA (GABA(A)) receptor alpha1-/- mice exhibit postural and kinetic tremor and motor incoordination that is characteristic of essential tremor disease. We tested mice with essential-like tremor using current drug therapies that alleviate symptoms in essential tremor patients (primidone, propranolol, and gabapentin) and several candidates hypothesized to reduce tremor, including ethanol; the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801; the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA); the GABA(A) receptor modulators diazepam, allopregnanolone, and Ro15-4513; and the L-type Ca2+ channel antagonist nitrendipine. Primidone, propranolol, and gabapentin reduced the amplitude (power) of the pathologic tremor. Nonsedative doses of ethanol eliminated tremor in mice. Diazepam, allopregnanolone, Ro15-4513, and nitrendipine had no effect or enhanced tremor, whereas MK-801 and CCPA reduced tremor. To understand the etiology of tremor in these mice, we studied the electrophysiological properties of cerebellar Purkinje cells. Cerebellar Purkinje cells in GABA(A) receptor alpha1-/- mice exhibited a profound loss of all responses to synaptic or exogenous GABA, but no differences in abundance, gross morphology, or spontaneous synaptic activity were observed. This genetic animal model elucidates a mechanism of GABAergic dysfunction in the major motor pathway and potential targets for pharmacotherapy of essential tremor.

Adrenergic beta-Antagonists↗
PubMed1977

Salivary levels of anticonvulsants: a practical approach to drug monitoring.

Phenobarbital, phenytoin, carbamazepine, primidone, and ethosuximide were measured in saliva and plasma obtained simultaneoulsy from 115 patients. A method to correct for the effect of salivary pH on phenobarbital concentration of saliva was developed. Salivary concentrations of these drugs were found to be equivalent to the plasma free drug and to correlate closely with the total plasma levels. Expressed as percent of total plasma drug, the salivary (S) and plasma free (P) concentrations were: phenytoin, S 11.1 +/- 2.0 percent (mean +/- SD), P 10.1 +/- 2.4 percent (r = 0.97); carbamazepine, S 26.0 +/- 2.4 percent, P 25.9 +/- 3.4 percent (r = 0.97); phenobarbital, S 43.1 +/- 5.2 percent, P 40.8 +/- 7.9 percent (r = 0.91); primidone, S 75.4 +/- 24.9 percent, P 66.4 +/- 8.8 percent (r = 0.76). Ethosuximide was not bound by plasma proteins, and its plasma and salivary levels were equal.

Anticonvulsants↗