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Biomedical subjects

F J Vajda

Publications and source records attributed to F J Vajda.

At least 37 records · Page 2Linked to original sources
PubMed1985

Clinical experience with clobazam: a new 1,5 benzodiazepine in the treatment of refractory epilepsy.

A benzodiazepine drug, clobazam, was evaluated in 14 refractory epileptic patients, nine of whom received the drug double-blind. Ten patients have been given clobazam long enough to assess results. Four showed marked benefit, four failed to respond and two showed a transient benefit which was maintained by dose changes of both clobazam and clonazepam. Side effects were minimal; doses ranged from 15 to 60 mg per day. Clobazam may have place in the treatment of the Lennox Gastaut syndrome and other types of refractory seizures.

Adolescent↗
PubMed1984

Effect of cimetidine and ranitidine on carbamazepine and sodium valproate pharmacokinetics.

The pharmacokinetics of a single oral dose (400 mg) of carbamazepine and sodium valproate were compared in peptic ulcer patients before and after four weeks of a therapeutic course of either cimetidine (1 g/day, n = 6 subjects) or ranitidine (300 mg/day, n = 6 subjects). There was a small (up to 20%) but statistically significant decrease in oral clearance of carbamazepine after cimetidine treatment. A similar fall in sodium valproate clearance in five cimetidine-treated patients was accompanied by a significantly prolonged elimination half-life. No such trends were demonstrated during ranitidine treatment. Since both anticonvulsants are partly metabolized by hepatic mixed function oxidases, an inhibition by cimetidine at this level may be responsible for the observed impairment of clearance. Thus a potentially important clinical interaction may occur in patients taking anticonvulsants and cimetidine concurrently.

Carbamazepine↗
PubMed1984

Drug treatment of epilepsy.

The most important factors in drug management of epilepsy are an accurate diagnosis of the type of seizures; the use of a first line drug as sole therapy for some weeks; and adjustment of the dose, according to plasma levels, to give maximum benefit.

Anticonvulsants↗
PubMed1984

Experience with continuous ambulatory EEG monitoring.

The value of continuous ambulatory EEG monitoring in the management of patients with seizures was assessed. Eighty-seven patients were studied over a two-year period, and 198 recordings were made. In six patients data from the monitor record changed management significantly by suggesting a diagnosis other than that made clinically and by routine EEG. In a further 33 patients data strongly supporting the clinical diagnoses were obtained. In 47 patients no positive diagnostic data were obtained, and in one patient the data could not be reconciled with the clinical picture. The ambulatory EEG was particularly useful for detecting nocturnal fits, such as tonic seizures, and for differentiating genuine seizures from pseudoseizures. Limitations of the instrument include the presence of only four channels and some distortion and degradation of the EEG signal. In spite of these problems, the instrument was found to be a valuable aid in the evaluation of patients with seizures.

Adolescent↗
PubMed1983

Reassessment of the concept of a therapeutic range of anticonvulsant plasma levels.

The significance of plasma-level measurements of anti-epileptic drugs is reviewed, especially as it applies to the treatment of childhood epilepsy. The problems associated with the determination and interpretation of 'therapeutic' levels are discussed, including the justification of applying to children the results of studies of adults. It is concluded that plasma-level determinations are of great value in specific circumstances, but that more study is needed to take into account the multiplicity of variables involved.

Anticonvulsants↗
PubMed1983

Use of drugs in the treatment of anxiety.

Anxiety is a common problem and often its treatment is inappropriate. Many classes of drugs have been used and benzodiazepines are the mainstay of treatment. Although drugs in this group are almost equivalent in their anxiolytic and hypnotic effects there are differences between their pharmacological characteristics and dosage schedules.

Adrenergic beta-Antagonists↗
PubMed1983

Hepatotoxicity of sodium valproate.

Repeated clinical and biochemical evaluations of liver function were performed on 60 patients taking sodium valproate. No clinical evidence of liver disease was found. Biochemical abnormalities were frequently found, but they were far more common in patients treated with multiple anticonvulsants than in patients on valproate alone. A control group of patients taking phenytoin or carbamazepine monotherapy also had a high incidence of biochemical abnormalities. A group of patients started on valproate therapy 6 years previously was followed up. No evidence of liver disease was found in this group. It was concluded that biochemical abnormalities of liver function in patients receiving valproate are not progressive, and in many cases relate to the intake of other drugs. The finding of abnormal liver function tests is not necessarily an indication for ceasing valproate.

Adolescent↗
PubMed1982

The relationship between alpha 2-adrenoceptor selectivity and anticonvulsant effect in a series of clonidine-like drugs.

Clonidine and the 4 clonidine-like drugs: 44-549, lofexidine, guanfacine, and CP-14,304-18, had anticonvulsant activity against pentylenetetrazole-induced convulsions in rats. The magnitude and dose range over which anticonvulsant effects were observed was related to the selectivity of the compounds for alpha 2 and alpha 1 adrenoceptors. Selective alpha 2 adrenoceptor agonists may form a new group of anticonvulsants.

Animals↗
PubMed1982

Anticonvulsant effects of clonidine mediated through central alpha2-adrenoceptors.

The effects of centrally (0.3-30 ng/kg) and peripherally (0.01 microgram/kg-1.0 mg/kg) administered clonidine on PTZ-induced seizures was studied in rats. At low doses, dose-dependent decreases in the duration of seizures was observed but at higher doses the duration returned to control levels. Anticonvulsant activity was antagonized by yohimbine (100 microgram/kg i.p.) indicating alpha2-adrenoceptor involvement, whereas the second phase of the response was antagonized by prazosin (10 ng/kg i.c.v.) indicating that it involved alpha1-adrenoceptors.

Animals↗
PubMed1982

Role of central beta-adrenoceptors in the control of pentylenetetrazol-induced convulsions in rats.

1 The role of central beta-adrenoceptors in the anticonvulsant effect of beta-adrenoceptor antagonists has been examined. 2 Oral administration of (-)- and (+)-propranolol (0.05-1 mg/kg) and (+/-)-pindolol (0.025-0.5 mg/kg) produced a dose-dependent decrease in duration of convulsions produced by pentylenetetrazol (PTZ 50 mg/kg, i.p.) in rats. 3 At the EC50 level, (-)-propranolol is seven times more effective than the (+)-isomer. 4 Oral administration of (-)-, (+)- or (+/-)-practolol (1-10 mg/kg) or (-)- or (+)-timolol (1-10 mg/kg), two beta-adrenoceptor antagonists that do not penetrate the blood brain barrier, had no significant effect on the duration of PTZ-induced convulsions. 5 Intracerebroventricular administration of (-)-propranolol (0.5 microgram/kg) or (-)-timolol (0.25 microgram/kg) produced highly significant anticonvulsant effects whereas the (+)-isomers at the same dose level were ineffective. (+/-)-Pindolol (0.25 microgram/kg) was also much more effective given by this route than when given orally. The (+)- and (-)-isomers of the beta 1-adrenoceptor selective antagonist practolol (10 microgram/kg) exerted only weak anticonvulsant effects. 6 This study provides evidence that beta-adrenoceptor antagonists exert an anticonvulsant effect through central beta 2-adrenoceptors. At high dose levels, additional anticonvulsant activity is associated with membrane stabilization in those antagonists which possess this property.

Adrenergic beta-Antagonists↗
PubMed1981

Renal clearance of methotrexate in man during high-dose oral and intravenous infusion therapy.

The renal excretion and clearance of methotrexate (MTX) following high-dose (800 mg) therapy followed by folinic acid rescue was studied in 12 patients (2 female, 10 male): the mean age was 49.3 +/- 5.5 (SE), weight 68.6 +/- 3.9 (SE) and body surface area 1.8 +/- 0.1 m2. Plasma and urine were collected over 154 h at intervals of 2-24 h, and the collection times, volume, and pH of urine samples recorded. Total MTX concentrations in urine and plasma were measured by the highly specific competitive protein-binding assay method. Plasma and urinary creatinine levels were measured on an SMA-12 autoanalyser. The renal clearance of MTX was calculated for each urine collection period. Following oral administration, clearance values during the first 6 h were high at 257 +/- 8.3 (ml/Min), followed by a trough in clearance of 27.9 +/- 4.2 (ml/min) in the 20- to 30-h period. This was followed by a secondary rise of MTX renal clearance to 180.4 +/- 14.6 ml/min during the 68- to 84-h period and again to 84.9 +/- 17.1 ml/min between 84 and 112 h. In the last two periods it rose to 209 +/- 57.9 ml/min. Similar fluctuations were seen following IV administration. The changes in clearance were statistically significant at the p less than 0.005 level. It is suggested that high concentrations of MTX in the renal tubules result in inhibition of carrier protein synthesis, leading to a fall in active tubular secretion. When MTX concentrations fall the tubular cell recovers and a secondary rise in renal clearance occurs, leading to cyclical changes in MTX elimination.

Administration, Oral↗
PubMed1981

Human brain, plasma, and cerebrospinal fluid concentration of sodium valproate after 72 hours of therapy.

Nine neurosurgical patients suffering from a variety of brain tumors were studied. Sodium valproate was given for 3 days before surgery. At craniotomy, sections of brain and samples of cerebrospinal fluid (CSF) and plasma were obtained and assayed for sodium valproate concentrations. Brain levels were 6.8 to 27.9% of plasma concentrations, and CSF levels were 7.6 to 25.0% of plasma levels. There was a significant correlation between brain and CSF levels and plasma on Spearman ranking. These results confirm that valproate is not selectively concentrated in brain fractions, and the concentration in brain is related to the free anticonvulsant level in plasma.

Adolescent↗