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At least 973 records · Page 54Linked to original sources
PubMed1990

Seizure susceptibility & intra rectal sodium valproate induced recovery in developing undernourished rats.

The seizure threshold and therapeutic potential of intrarectal sodium valproate were studied in young developing normal and undernourished rats, using the penicillin model. Undernourished rats were highly susceptible to seizure discharge. They exhibited generalised electrocortical inhibition and repeated episodes of epileptic discharges even after temporary neuronal recovery. Delayed spontaneous and drug induced neuronal recovery, low spike frequency and amplitude (P less than 0.001) reduced background EEG and marked electrocortical silence in response to intrarectal (25 mg/kg) sodium valproate treatment, was observed in the undernourished animals. Rehabilitated animals exhibited partial neuronal recovery which was related to the improvement in body weight. Analysis of spike frequency, spike amplitude and neuronal recovery time showed that both normal and undernourished animals behaved in a similar fashion at lower doses of penicillin (2.5 to 15 IU). Significant differences in the electrophysiological parameters were observed between the two groups at higher doses of penicillin (20 to 30 IU).

Administration, Rectal↗
PubMed1990

Therapeutic levels of valproate for psychosis.

Valproic acid was added to the treatment regimens of 21 psychiatric inpatients whose response to antipsychotic medications had been inadequate, and steady-state serum valproate levels were obtained on 15. The 7 patients who had unequivocal positive therapeutic responses to valproate improved at a mean serum level of 68, with a 95 percent confidence interval of 50 to 86. The 8 nonresponders had a mean serum level of 37.5 with a 95 percent confidence interval of 13 to 62. There was a weak relationship between oral dose and serum level. Two patients never reached therapeutic levels in spite of oral daily dosages of 5 g and 6 g respectively. Therapeutic levels could not be reached by 7 patients (47%) who were taking more than 1,250 mg daily. Our results suggest that the therapeutic serum range for seizures is valid for psychiatric patients but that the usual suggested oral dosage is often inadequate. Drug interactions may account for this.

Humans↗
PubMed1987

[Prenatal diagnosis of 4 cases of spina bifida in mothers treated with valproate].

The potential risk of spina bifida (SB) after fetal exposure to Valproate led the authors to apply the following protocol: in case of first trimester exposure to Valproate, prenatal diagnosis is offered and consists of both amniotic fluid examination and fetal ultrasound to detect open spina bifida. In the period 1983 to June, 1986, this program allowed early detection of three cases of SB and pregnancy termination. Another case escaped the programme: neural tube defect was detected lately and the child had to be operated upon. These four cases of SB underline the necessity of prenatal diagnosis with combined use and confrontation of ultrasound examination and biochemical amniotic fluid tests.

Adult↗
PubMed1989

Emerging perspectives on valproate in affective disorders.

The anticonvulsants, especially carbamazepine and valproate, offer new clinical and theoretical perspectives in the treatment of lithium-refractory bipolar disorders. They appear effective in a group of patients who often respond poorly to lithium, that is, those with rapid cycling illness. Given that these drugs have different profiles of clinical antiepileptic activity and different biochemical mechanisms of action, it is not unexpected that preliminary evidence indicates that some affectively ill patients may selectively respond to one, but not the other, agent. It remains to be determined whether common mechanisms underlie the anticonvulsant and psychotropic effects and whether "limbic" actions are important to their properties in affective illness. The potential role of valproate in acute and long-term treatment of bipolar illness deserves further controlled evaluation given the preliminary data summarized in the series of papers in this volume.

Adult↗
PubMed1989

Distribution of drugs over whole blood: I. The transport function of whole blood for valproate.

A method is presented for the determination of valproate (VPA) in approximately 40 microliters erythrocyte concentrations. Valproate partition between plasma proteins, ultrafiltrate, and erythrocytes at various concentrations was studied in vitro and in vivo. Partition ratios depended on VPA concentration in whole blood and the ratio of erythrocytes/ultrafiltrate, which increased with rising concentrations in the ultrafiltrate fraction. Shifts in ratios were studied by expanding the ultrafiltrate fraction of VPA-spiked blood. It appeared that VPA delivery to the expanded ultrafiltrate compartment originated in a disproportionately large part from erythrocytes. In vivo the half-life of VPA in the erythrocyte fraction was 0.7 h, whereas in the ultrafiltrate fraction and protein-bound fraction half-lives of 2 and 5 h were observed. It is concluded that for VPA in relation to erythrocytes a "last-come-first-go" system is plausible.

Blood Proteins↗
PubMed1989

Sleep disorders and depression with atypical features: response to valproate.

Symptoms of so-called atypical depression, such as hypersomnia and lethargy, may accompany specific sleep disorders. It is often difficult to determine which disorder is "primary". The authors examine three cases of depression with atypical features associated with specific sleep disorders and report a favorable response to valproate. Some clinical features of the cases suggest a primary sleep disorder with secondary affective symptoms. However, valproate may have direct mood-altering effects as well as effects on sleep physiology. The implications of these findings for diagnosis and treatment are discussed.

Adult↗
PubMed1989

Effects of sodium valproate and oxygen on the craniofacial skeletal pattern in the CD-1 mouse embryo.

Growth retardation is a consistent finding in animal studies on the effect of sodium valproate (NaVP) in the embryo. Apart from fetal weight, the state of ossification in the embryo may be regarded as an indication of growth. The present study was to determine what effect sodium valproate at human therapeutic drug plasma levels had on the craniofacial skeletal pattern in the CD-1 mouse embryo relative to oxygen conditions, drug treatment or the interaction of the two. Two NaVP-filled Alzet osmotic minipumps were implanted subcutaneously on day 5 of gestation for continuous delivery of a total daily dosage of 850 mg/kg for 7 days. During this same time period the dams were also exposed to either normoxic (21% oxygen), hyperoxic (50% oxygen), or hypoxic (12% oxygen) controlled environments. Dams were removed from the oxygen chambers on day 12 and killed on day 18 of gestation. The fetuses were then processed for skeletal evaluation of the craniofacial region. Ossification centers were present in all but six of the skeletal elements studied. The primary ossification delay was in the tympanic bony labyrinth. In addition, there was a decrease in maxillary and mandibular length and cranial base measurements. The greatest toxic effect on the fetus for all skeletal components studied was in the NaVP/hypoxia treated group. This finding suggests that fetal skeletal maturation may be affected by a combination of intrauterine as well as external factors.

Animals↗
PubMed1985

[Effect of diazepam, carbamazepine, sodium valproate and their combinations with vitamin preparations on epileptic activity].

The anticonvulsive action of diazepam, carbamazepine, sodium valproate and their combinations with pyridoxal-5-phosphate, nicotinamide, and alpha-tocopherol were investigated in acute experiments on mice with corazole-induced seizures. Diazepam (0.5 mg/kg), carbamazepine (50 mg/kg) and sodium valproate (200 mg/kg) were shown to reduce convulsive intensity and lethality. Vitamins nicotinamide (250 mg/kg), pyridoxal-5-phosphate (10 mg/kg) and alpha-tocopherol (100 mg/kg) potentiated anticonvulsive action of the above antiepileptic drugs. The results of the investigation suggest the efficacy of pathogenetic therapy and give new evidence of the advisability of using vitamins in combination with synthetic anticonvulsive drugs.

Animals↗
PubMed1985

Influence of valproate and carbamazepine on symmetrical cortical penicillin foci in the rat.

Two epileptogenic foci were formed in homotopic areas of sensorimotor cortices of both hemispheres by application of penicillin. Both valproate (200 and/or 400 mg/kg i.p.) and carbamazepine (50 and/or 100 mg/kg i.p.) did not significantly alter the synchronization of interictal focal discharges. The incidence of ictal phases was suppressed by both drugs in a dose-dependent manner--higher doses (valproate--400 mg/kg; carbamazepine--100 mg/kg i.p.) fully blocked the seizures. Both drugs did not suppress the projection of focal discharges into the opposite hemisphere but were efficacious against secondary generalization.

Animals↗
PubMed1986

Use of ethosuximide and valproate in the treatment of epilepsy.

Ethosuximide is the drug of first choice in absence seizures. Idiosyncratic side effects are rare. Valproate is effective against absence, generalized tonic-colonic, and partial seizures. It is the drug of choice in photosensitive seizures. Valproate is, on the whole, free from unpleasant side effects, but fatal hepatotoxicity and hyperamnionemia have been reported very rarely.

Abnormalities, Drug-Induced↗
PubMed1987

The management of epilepsy in women of child-bearing age and the Australian experience of valproate in pregnancy.

Published opinion is reviewed and summarized with special reference to the teratogenic potential of the newer anticonvulsant drugs, treatment decisions and patient supervision. An Australian report covering a period of eight years, summarizing congenital malformations in births to patients whose treatment included sodium valproate (EpilimR) is presented against the background of the WHO report on valproate and pregnancy.

Abnormalities, Drug-Induced↗
PubMed1987

[Preventing the recurrence of febrile seizures: intermittent prevention with rectal diazepam compared with continuous treatment with sodium valproate].

Sixty nine children suffering from a first febrile seizure without evidence of neurologic disorder or associated risk factors were randomly assigned to one of three groups: no treatment; intermittent rectal diazepam; or continuous oral sodium valproate. All patients were followed for two years. Periodical controls were performed every three months in order to record febrile episodes, recurrent seizures, and treatment side affects. Rate of recurrent febrile seizures was 16% in control group, and 5.5% in diazepam group. Sodium valproate group showed no recurrences in the follow-up period. The low relapsing rate in control group suggests that prophylaxis should not be established even if it is requested by certain parental attitudes.

Administration, Rectal↗
PubMed1988

Valproate-induced stimulation of renal ammonia production and excretion in the rat.

Administration of valproate, a widely used antiepileptic drug, markedly stimulated the production of ammonia by the rat kidney, resulting in an increase in both the renal venous release and the urinary excretion of ammonia. These effects were associated with a diminution of the plasma concentration of urea which was not accompanied by a stimulation of the urinary excretion of urea. These results indicate that the kidneys, together with the liver, might contribute to the hyperammonaemia caused by valproate.

Ammonia↗
PubMed1988

Valproate in the treatment of rapid-cycling bipolar disorder.

Six consecutive patients with rapid-cycling bipolar disorder, refractory or only minimally responsive to treatment with lithium salts and neuroleptics, including five also refractory to carbamazepine, all demonstrated a moderate or marked response to the anticonvulsant valproate. These observations suggest that valproate may represent a promising treatment alternative in this often treatment-resistant form of bipolar disorder.

Adult↗
PubMedDate not supplied

[Comparative study of preparations of sodium and magnesium valproate (VPA) in treatment of patients with epileptic seizures].

A double blind cross over trial of Sodium Valproate (Na VPA) vs Magnesium Valproate (Mg VPA) was performed in 122 patients affected by focal or generalized epilepsies. Only modest differences resulted from the comparison between the two drugs: retention was 8% superior in patients treated with Mg VPA, the number of critic episodes and the quantification of interictal events was significantly lower in patients affected by focal epilepsy treated with Mg VPA. The incidence of side effects was the same for the two drugs.

Adolescent↗
PubMed1978

Sodium valproate (Epilim) in the treatment of refractory epilepsy.

Sodium valproate was given to seven children with refractory epilepsy and mental retardation. Four of the children became fit free while another was much improved. Plasma levels of sodium valproate correlated well with the dose prescribed and did not approach the theoretical top-desirable level of 200 microgram/ml despite larger than recommended doses. Side effects were minimal and it is concluded that the drug is safe and useful.

Adolescent↗