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At least 595 records · Page 33Linked to original sources
PubMed1994

The relationship of essential tremor to other movement disorders: report on 678 patients. Essential Tremor Study Group.

We examined 678 essential tremor patients in specialty, university, and private practice clinics. The mean age of patients was 65.2 years with a similar number of men and women. Six percent of patients were left-handed. A positive family history of tremor was reported in more than 60% of patients. Alcohol ingestion was reported to decrease tremor in 74% of patients who were cognizant of the effect of alcohol on tremor. Mean age at tremor onset was 45.3 years. An earlier onset of tremor was observed in those patients having a positive family history of tremor. Tremor affected the hands in 90% of patients, head in 50%, voice in 30%, and legs and chin in 15%. Functional disability was common and impairment at work occurred in 18%. Propranolol and primidone were the most frequently used drugs and were effective in 40% of patients. Six and one-tenth percent of essential tremor patients had concomitant Parkinson's disease, 6.9% had a coexisting dystonia, and 1.8% had myoclonus. It is concluded that the frequency of Parkinson's disease in essential tremor is more than would be reported in the general population and that other movement disorders are infrequently observed in essential tremor.

Aged↗
PubMed1986

Automated and routine liquid chromatographic analysis of antiepileptic drugs.

We describe an optimized automated liquid chromatographic method for simultaneous measurement of primidone, phenobarbitone, phenytoin, carbamazepine and clonazepam. A Waters Tri-Module automation system is used and it provides direct read-out of results after chromatography. A one-step extraction with ethyl acetate is used to extract the drugs from 100 microL serum samples. We use an isocratic mobile phase and monitor the column effluent at 210 nm. Drug levels as low as 5 mumol/L can be detected. The within-run CV's range from 1.4 to 2.7%, and the between-run CV's range from 5.2 to 6.1%. Analytical recovery is in the range from 94-108%. The method compares favourably with the enzyme multiple immunoassay technique for routine antiepileptic drugs monitoring, in accuracy, efficiency and cost-effectiveness.

Anticonvulsants↗
PubMed1979

Kinetics and metabolism of carbamazepine during combined antiepileptic drug therapy.

The kinetics of carbamazepine using 15N-carbamazepine were investigated in epileptic patients during combined anticonvulsant therapy. The 15N-carbamazepine plasma half-lives ranged from 5.0 to 13.6 hr with a mean of 8.2 hr. These half-lives are appreciably shorter than reported during chronic carbamazepine monotherapy. Predicted steady-state plasma levels and observed plasma levels of carbamazepine were in excellent agreement. Between 32% and 61% of the dose administered is excreted in the urine as carbamazepine-trans-diol, 5.2% to 8.8% as 9-hydroxymethyl-10-carbamoyl acridane, 1% to 1.4% as 10,-11-carbamazepine epoxide, and 0.5% as carbamazepine. The data indicate that it is the epoxide-diol pathway which is induced during long-term treatment. Concomitant therapy with primidone, phenytoin, phenobarbital, ethosuximide, or methsuximide further induces carbamazepine metabolism.

Adult↗
PubMed2003

Microemulsion electrokinetic chromatography applied for separation of levetiracetam from other antiepileptic drugs in polypharmacy.

Microemulsion electrokinetic chromatography was applied for the separation of levetiracetam from other antiepileptic drugs (primidone, phenobarbital, phenytoin, lamotrigine and carbamazepine) that are potentially coadministered in therapy of patients. The influence of the composition of the microemulsion system (with sodium dodecyl sulfate as charged surfactant) was investigated, modifying the kind of cosurfactant (lower alcohols from C3 to C5), the pH (and salinity) of the aqueous background electrolyte, and the ratio of aqueous phase to organic constituents forming the microdroplets of the oil-in-water emulsion. Separation selectivity was depending on all these parameters, resulting even in changes of the migration sequence of the analytes. Only moderate correlation was observed for the microemulsion system compared with a micellar system, both consisting of the aqueous borate buffer (pH 9.2) and SDS as micelle former (linear correlation coefficient for analyte mobilities is 0.974). The sample solvent plays an important role on the shape of the resulting chromatograms: methanol at concentrations higher than 35% impairs peak shape and separation efficiency. The microemulsion method (with 93.76% aqueous borate buffer (pH 9.2, 10 mM), 0.48% n-octane, 1.80% SDS, 3.96% 1-butanol, all w/w) is suitable for the determination of levetiracetam in human plasma (combined with a sample pretreatment based on solid-phase extraction).

Anticonvulsants↗
PubMed1994

Hepatic cytochrome P450 2B induction by ethyl/phenyl-substituted congeners of phenobarbital in the B6C3F1 mouse.

The abilities of structural congeners of phenobarbital to induce immunoreactive hepatic cytochrome P450 2B (CYP2B) protein and associated catalytic activity (benzyloxyresorufin O-dealkylation) in the male B6C3F1 mouse were examined. Interspecies differences in inducing ability were examined through comparison of the results with induction data obtained previously with the male F344/NCr rat. The congeners were administered in the diet for 2 weeks at concentrations equimolar to 500 ppm of the prototype CYP2B inducer, phenobarbital. Of the series of compounds tested, phenobarbital was the most effective inducer of benzyloxyresorufin O-dealkylation and immunoreactive CYP2B protein, with 2-ethyl-2-phenylsuccinimide, 5-ethyl-5-phenylhydantoin, primidone, and glutethimide being only 19-42% as effective. 5-Ethyl-5-phenyloxazolidinedione and the ring-opened and decarboxylated congeners, N-(2-ethyl-2-phenylacetyl)urea and 2-ethyl-2-phenylmalonamide, displayed minimal induction of these catalytic activities. Dose-response experiments performed with 5-ethyl-5-phenylhydantoin indicated that the intrinsic CYP2B-inducing activity of this congener was as great as that of phenobarbital in the mouse, although a fourfold greater dietary concentration of this hydantoin (2000 ppm) was required to elicit a response equivalent to that caused by 500 ppm phenobarbital. When extent of induction was related to serum total xenobiotic concentration rather than to administered dietary concentration, the potencies of the two congeners were determined to be more similar (58 vs. > or = 78 microM for phenobarbital and 5-ethyl-5-phenylhydantoin, respectively).

Animals↗
PubMed2004

Natural history and syndromic associations of orthostatic tremor: a review of 41 patients.

Orthostatic tremor (OT) is a rare condition characterized by unsteadiness when standing still that is relieved when sitting or walking and is thought to arise from a central generator in the cerebellum or brainstem. OT is considered to be a distinct, discrete condition, and little is known about its demographic characteristics, natural history, associated features, and treatment response. We have reviewed these aspects in 41 OT patients fulfilling current diagnostic criteria, seen at our institution between 1986 and 2001. We classified 31 (75%) as having idiopathic "primary OT" either with (n = 24) or without an associated postural arm tremor. We found that 10 of 41 (25%) cases had additional neurological features, and we defined this group as having "OT plus" syndrome. Of these 10, 6 had parkinsonism; 4 of these had typical Parkinson's disease (PD), 1 had vascular and 1 had drug-induced parkinsonism. Among the remaining 4 patients, 2 had restless legs syndrome (RLS), 1 had tardive dyskinesia, and 1 orofacial dyskinesias of uncertain etiology. One patient with PD and the patient with vascular parkinsonism also had RLS. Age at onset was significantly earlier in the "primary OT" (mean +/- SD, 50.4 +/- 15.1) than in the "OT plus" (61.8 +/- 6.4; z = 2.7; P =.006) group. In 7 of the 10 "OT plus" patients, OT leg symptoms preceded the onset of additional neurological features. OT appeared to be underdiagnosed, and on average, it took 5.7 years from the initial complaints until a diagnosis was made. In general, treatment response to a variety of drugs such as clonazepam, primidone, and levodopa was poor. In most cases, OT symptoms remain relatively unchanged over the years, but in 6 of 41 cases (15%), the condition gradually worsened over the years, and in some of these cases, symptoms spread proximally to involve the trunk and arms. OT may not be a discrete disorder as commonly believed and associated features like parkinsonism present in nearly 25% of cases. Dopaminergic dysfunction may have a role in the pathophysiology of this disorder.

Aged↗
PubMed1993

Effectiveness of piracetam in cortical myoclonus.

Twenty-one patients with disabling spontaneous, reflex, or action myoclonus due to various causes, who had shown apparent clinical improvement on introduction of piracetam, entered a placebo-controlled double-blind crossover trial of piracetam (2.4-16.8 g daily). All but one patient had electrophysiological evidence of cortical myoclonus. Patients were randomly allocated to a 14-day course of piracetam followed by identical placebo, or placebo followed by piracetam. Nineteen patients received piracetam/placebo in addition to their routine antimyoclonic treatment (carbamazepine, clonazepam, phenytoin, primidone, sodium valproate, or tryptophan plus isocarboxazid, alone or in combination) and two received piracetam/placebo as monotherapy. All patients were rated at the end of each treatment phase using stimulus sensitivity, motor, writing, functional disability, global assessment, and visual analogue scales. Ten of the 21 patients had to be rescued from the placebo phase of the trial because of a severe and intolerable exacerbation of their myoclonus. No patients required rescue from the piracetam phase of the double-blind trial. When the 21 patients were considered together, there was a significant improvement in motor, writing, functional disability, global assessment, and visual analogue scores during treatment with piracetam compared with placebo. The total rating score also improved significantly with piracetam, by a median of 22%. Piracetam, usually in combination with other antimyoclonic drugs, is a useful treatment for myoclonus of cortical origin.

Adult↗
PubMed1998

Pharmacologic treatment of tremor.

Tremor is a common neurologic symptom that can also be incapacitating to the patient, so effective therapy is needed. The causes of tremor are heterogeneous. Essential tremor (ET) and the tremor associated with Parkinson's disease (PD) are the most common encountered in clinical practice. Beta-adrenergic blockers and primidone remain the mainstay of treatment for ET, whereas carbidopa/levodopa and anticholinergics are most beneficial in PD. However, the efficacy of various other medications has been studied in ET and PD, and also in patients with tremor resulting from other conditions, with varying results.

Humans↗
PubMed1993

Hydantoin syndrome with holoprosencephaly: a possible rare teratogenic effect.

We report on a newborn girl with lobar holoprosencephaly and clinical signs of hydantoin syndrome. During pregnancy the mother was treated with diphenylhydantoin and primidon for psychomotor and petit mal seizures. The possible relationship between hydantoin syndrome, holoprosencephaly, and maternal intake of anticonvulsants during pregnancy is discussed.

Abnormalities, Drug-Induced↗
PubMed1996

Antiepileptic drug pharmacokinetics in patients with epilepsy using a new microdialysis probe: preliminary observations.

Using a newly developed microdialysis probe which allows continuous monitoring of drugs in blood, we have studied the pharmacokinetics of various antiepileptic drugs (carbamazepine, and its primary metabolite carbamazepine-epoxide, phenytoin primidone and phenobarbitone) in 5 patients (2 male, 3 female, aged 40-50 years) with intractable epilepsy. It was observed that microdialysate pharmacokinetic profiles were comparable to those obtained by direct blood sampling. Furthermore, patients found the microdialysis probe highly acceptable and desirable and indeed preferable to that of blood sampling.

Adult↗
PubMed1987

Discriminative stimulus properties of ethosuximide in the pigeon.

After initial exposure to 80 mg/kg, pigeons trained on a two-key drug discrimination procedure rapidly learned to discriminate 120 mg/kg ethosuximide from saline. When 40-160 mg/kg doses of ethosuximide were administered during generalization tests, the percentage of responses directed to the ethosuximide-appropriate key varied directly with dose. Time-effect determinations revealed that the discriminable properties of ethosuximide were evident as early as 15 min after, and as late as 2 h after, intramuscular injection. The discriminative stimulus properties of ethosuximide failed to generalize to the anticonvulsant compounds clonazepam (0.5-4 mg/kg), methsuximide (25-200 mg/kg), and phenytoin (5-15 mg/kg). Generalization was apparent with certain doses of primidone (250, 300 mg/kg) and mephenytoin (80, 160, 240 mg/kg). The concomitant administration of pentylenetetrazol (5, 10, 20 mg/kg) partially blocked the discriminable properties of the training dose of ethosuximide.

Animals↗
PubMed1980

Role of striatal acetylcholine and free ammmonia in the central stimulatory effects of pp'DDT in rats. Protective effects of barbiturates.

pp'DDT (600 mg/kg, orally) produced an increase in the level of free ammonia and a decrease of acetylcholine in the corpus striatum of rats. These effects were maximal 5 h after the administration of pp'DDT. The animals showed tremors after 2 h, mild or moderate convulsions after 3.5 h and severe convulsions 5 h after treatment with pp'DDT. The neurochemical changes and convulsions induced by pp'DDT were modified to different degrees by barbiturates. Phenobarbitone sodium abolished the convulsions while prominal reduced the severity of convulsions in pp'DDT treated animals. The level of striatal acetylcholine in pp'DDT-phenobarbitone treated animals was not significantly different from the control values. In prominal-pp'DDT treated animals, it was slightly but significantly reduced. Primidone neither changed the severity of convulsions nor the level of striatal acetylcholine in pp'DDT treated animals. Further barbiturates had no significant effect on the level of free ammonia in pp'DDT treated rats. The results suggest that changes in the level of acetylcholine are not the cause but an effect of pp'DDT induced stimulatory effects or convulsions, mediated through an increase in the level of free ammonia or some other mechanism.

Acetylcholine↗
PubMed1982

Therapeutic drug monitoring: a comprehensive and critical review of analytical methods for anticonvulsive drugs.

In the last 20 years, there has been considerable improvement in the determination of anticonvulsive drugs in body fluids. Gas-liquid chromatography, high-performance liquid chromatography and immunological methods (radio-, enzyme-, fluoro-, and nephelo-immunoassays) have progressively supplanted spectrophotometry and thin-layer chromatography. As the number of publications shows, these methods have included a great variety of procedures. At present, gas-liquid chromatography and enzyme-immunoassays are routinely performed, awaiting a wider spread of liquid chromatography and other immunological techniques. This paper is a comprehensive review of the analytical literature on the determination of phenobarbitone, primidone, phenytoin, carbamazepine, valproic acid, ethosuximide, clonazepam, and some of their metabolites in physiological fluids. Gas-liquid chromatographic methods are more particularly reviewed. In order to facilitate the choice between these procedures, a critical selection of the techniques is given and recommendations are made. Emphasis is laid on technical problems encountered with the assays, as well as the need for a rigorous analytical assessment and internal and external quality controls. This review is completed by considerations on the determination of the free drug fraction and on sample collection and storage.

Anticonvulsants↗
PubMed1982

Discriminative, disinhibitory, and depressant effects of several anticonvulsants.

The discriminative attributes of drugs were used to assess the degree to which several anticonvulsants have behavioral effects resembling those of pentobarbital. Rats were trained to make alternative responses to obtain water, depending on whether they had been injected IP with pentobarbital (10 mg/kg) or saline 10 min before the session. The pentobarbital response was chosen in tests with phenobarbital, dimethylphenobarbital, or methsuximide in the anticonvulsant dosage range. Increasing doses increased the percentage pentobarbital choice. Response rate was generally increased by doses that increased percentage of pentobarbital choice. The rats predominantly chose the saline response when administered phenytoin, primidone, or phenylethylmalondiamide, even at doses that were sufficiently high to reduce the response rate. The results suggest that different types of depressant effects are associated with the anticonvulsants tested.

Animals↗
PubMed1982

Plasma high-density lipoproteins and hepatic microsomal enzyme induction. Relation to histological changes in the liver.

The relationship between high-density lipoproteins (HDL) in plasma and hepatic structure and microsomal function has been investigated in 54 patients undergoing diagnostic liver biopsy. Plasma HDL cholesterol and major apoproteins were correlated with hepatic histology and microsomal enzyme activity assessed directly as liver cytochrome P-450 concentration and indirectly by plasma antipyrine clearance rate. HDL cholesterol, the concentrations of apoproteins A-I and A-II, the HDL cholesterol/total cholesterol ratio and cytochrome P-450 were low in subjects with moderate or severe hepatic fatty infiltration or cirrhosis when compared with the values for subjects with a normal live. HDL cholesterol and apoprotein A-I and the HDL cholesterol/total cholesterol ratio were directly proportional to the amount of non-fatty parenchyma in the livers. Subjects with a normal liver undergoing treatment with enzyme-inducing drugs, such as phenytoin, phenobarbital and primidone, had higher HDL cholesterol, apoproteins A-I and A-II, HDL cholesterol/total cholesterol ratio, cytochrome P-450 and antipyrine clearance rate than subjects not receiving such therapy. Treatment with inducers appeared to have compensated for the effect of liver disease in lowering plasma HLD. In the entire population, and also in subjects not taking inducing drugs, when considered separately, plasma HDL cholesterol, apoproteins A-I and A-II and the HDL cholesterol/total cholesterol ratio were significantly correlated with cytochrome P-450 concentration. In subjects on enzyme inducers, HDL cholesterol and apoprotein A-I levels and the HDL cholesterol/total cholesterol ratio were proportional to the magnitude of the induction. Serum triglycerides were inversely proportional to the measures of liver microsomal enzyme activity. The lipoprotein pattern, high HDL cholesterol and apoproteins A-I and A-II, and high HDL cholesterol/total cholesterol ratio that accompany microsomal induction are characterized by a reduced risk of atherosclerotic vascular disease and a prolonged expectation of life. The plasma changes presumably reflect the effect of enzyme inducers, such as phenytoin and phenobarbital on hepatic lipids and proteins.

Adult↗
PubMed1986

Antagonism of seizures induced by the administration of the endogenous convulsant quinolinic acid into rat brain ventricles.

The effect of pretreatment with drugs on generalized clonic-tonic seizures induced by intracerebroventricular (i.c.v.) administration of the endogenous convulsant quinolinic acid (QUIN, 50 micrograms) was studies in rats. Of the inhibitory amino acids tested, only 1-glycine (50 and 100 micrograms, i.c.v.) diminished the number of animals with seizures while taurine and GABA were ineffective. Of the kynurenine metabolites, only kynurenic acid (50 micrograms, i.c.v.) prevented seizures and lethality. Picolinic acid, nicotinic acid and nicotinamide were ineffective. The standard anticonvulsants phenobarbital, diphenylhydantoin and primidone were effective antagonists of QUIN-induced seizures at doses which did not influence pentylenetetrazol seizures. However, the only drug which completely prevented QUIN-induced seizures was diazepam (10 mg/kg). It also prevented pentylenetetrazol seizures in rats in a four times lower dose. The GABA derivatives sodium hydroxybutyrate and phenibut (beta-phenyl-GABA), which are effective QUIN-antagonists in mice, were found to be ineffective in rats. Species differences between rats and mice in the efficacy of antagonists QUIN are discussed.

Animals↗
PubMed1992

Influence of co-medication on the metabolism of valproate.

Valproate is extensively metabolized in the liver and at least six main pathways which produce about 50 metabolites have been identified in man. The enzyme-inducing antiepileptic drugs phenobarbital, primidone, phenytoin and carbamazepine increase total valproate clearance by 30-85%, whereas cimetidine and the new anticonvulsant compound striripentol display a small inhibitory effect (10-20%). Both carbamazepine and phenytoin induce a two-fold increase in the formation of delta 4-valproate and stimulate omega-oxidation and omega-1-oxidation. Acetylsalicylic acid causes a fall of 60-70% in the content in the urine of the metabolites of the beta-oxidative pathway, i.e. delta 2-valproate, 3-OH-valproate and 3-oxo-valproate, and an increase of glucuronidation (approximately 30%) and delta-dehydrogenation (approximately 20%). Stiripentol inhibits the formation clearance of delta 4-valproate by 30%. In the light of the possible therapeutic and toxic effects of some valproate metabolites, drug interactions with valproate at metabolic level may have important clinical implications.

Anticonvulsants↗
PubMed1990

Detection of anticonvulsants and their metabolites in urine within a "general unknown" analysis procedure using computerized gas chromatography-mass spectrometry.

Detection of the anticonvulsants carbamazepine, clonazepam, diazepam, ethosuximide, mephenytoin, mesuximide, methylphenobarbital, phenobarbital, phenytoin, primidone, propylhexedrine, sultiame, trimethadion and their metabolites in urine is described. The method presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs, detecting several hundred drugs and over 1000 metabolites. It includes cleavage of conjugates by acid hydrolysis, isolation by liquid-liquid extraction, derivatization by acetylation, separation by capillary gas chromatography and identification by computerized mass spectrometry. Using mass chromatography with the selective ions m/z 58, 104, 113, 117, 165, 193, 204 and 246, the possible presence of anti-convulsants and/or their metabolites was indicated. The identity of positive signals in the reconstructed mass chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The sample preparation, mass chromatograms, reference mass spectra and gas chromatographic retention indices are documented.

Anticonvulsants↗