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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seizures in the neonatal period are usually concomitants of serious neurological disease. The convulsive phenomena take certain distinctive and often subtle forms because of the status of the neuroanatomical and neurophysiological development of the neonatal brain. The predominant etiological process is hypoxic-ischemic encephalopathy, but intracranial hemorrhage, intracranial infection, development defects and metabolic disorders are also responsible for a considerable proportion of cases. Prognosis is related primarily to the neurological disease that underlies the seizures. Treatment may be specific for the underlying disorder, e.g., glucose, calcium, magnesium, pyridoxine, but whatever the cause, urgent control of the convulsions is important because they may have deleterious consequences. Phenobarbital is the single, most important anticonvulsant in the management of neonatal seizures.
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PMID:Management of neonatal seizures. 83

The effects of leptazol and bicuculline on the efflux of endogenous acetylcholine (ACh) from the surface of the cerebral cortex have been related to EEG activity in urethane-anaesthetised rats. During seizure activity there was a calcium dependent increase in ACh efflux which was related to increase EEG activity and clonic muscle movements. ACh release and EEG activity were reduced during convulsive activity by trimethadione but not phenytoin. Phenobarbitone reduced convulsive EEG activity but left ACh release relatively unaffected. Blood pressure changes induced by convulsant and anticonvulsant drugs were not consistently related to EEG activity or ACh release. It is suggested that ACh efflux from the cerebral cortex is closely related to the activity of neurones within the cortex where it is released from nerve endings. Comparison of EEG changes induced by anticonvulsants and urethane during control and convulsant activity showed that only trimethadione produces anticonvulsant activity unaccompanied by general CNS depression.
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PMID:Convulsant-anticonvulsant interactions on seizure activity and cortical acetylcholine release. 85 9

The plasma concentration of phenobarbital given as anticonvulsive treatment in the newborn period has been followed in 18 infants. With constant daily doses, the drug accummulated for at least 5 days. After intramuscular injection of a single dose, 90% of the peak concentration was reached within 4 hours in 8 of the 10 infants. The peak concentration (in mug/ml) approximately equalled 1.3 x the dose (in mg/kg). Absorption after oral administration was less reliable. In 12 of the infants the clinical course allowed attempts to evaluate the anticonvulsive effect of phenobarbital. In 4 cases the convulsions continued. In those 8 infants where phenobarbital seemed to be effective, the approximate range of phenobarbital concentration when convulsions ceased was 12-30 mug/ml. Phenobarbital half-life ranged between 59 and 182 hours. In some infants the rate of phenobarbital disappearance from the plasma varied considerably from day to day. The pathological conditions causing seizures probably influence the distribution, metabolism and excretion of the drug. For the often seriously ill infants with convulsions it is therefore difficult to construct rational maintenance dose schedules, and optimal dosage must be based on repeated determinations of the plasma concentration.
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PMID:Plasma concentrations of phenobarbital in the treatment of seizures in newborns. 115 69

The results of serum level determination in 250 epileptics confirm previous papers. Phenobarbital: --Is a "safe" anticonvulsant: steady serum level during 24 hours periods in chronic treatment and rather stable relationship between ingested dose and serum level. It can therefore be given as in the past, without blood level control. --Must always be prescribed according to the patient's weight, because serum level and therefore cerebral concentration depends on the dose per kilogram and not on the absolute dose. --Must be given in relatively higher dosage to children on account of a faster catabolism. --Is interfered with in its kinetics by other anticonvulsants and this fact must be taken into consideration for drugs associations. --Has no predetermined blood level for the control of every epilepsy. Some patients no longer have seizures with a theoretically too low serum level, while others still have seizures in spite of very high serum levels.
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PMID:[Serum phenobarbital levels in epileptics]. 122 Sep 57

The anticonvulsive properties of orally administered cinnarizine [(E)-1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine], its difluoro derivative flunarizine [(E)-1-(bis-(4-fluorophenyl)methyl)-4-(3-phenyl-2-propenyl)-piperazine], diphenylhydantoin and phenobarbital, were studied against maximal metrazol seizures (MMS) in rats and maximal electroshock seizures (MES) in mice. In rats (MMS), the lowest ED50 for protection against tonic extension of hindpaws was 4.10 mg/kg (1 h 35 min after treatment) with sodium phenobarbital, 6.04 mg/kg (5 h 45 min) with flunarizine dihydrochloride, 9.84 mg/kg (2 h 34 min) with cinnarizine and 19.30 mg/kg (3 h 38 min) with diphenylhydantoin. In mice (MES), protection against tonic extension of hindpaws was (2 h after treatment) 7.0 mg/kg with diphenylhydantoin, 13.2 mg/kg with sodium phenobarbital, 20.9 mg/kg with flunarizine kihydrochloride and 49.0 mg/kg with cinnarizine. Except at subtoxic doses no side effects were observed in rats and mice given cinnarizine, flunarizine kihydrochloride or kiphenylhydantoin. Phenobarbital induced ataxia in rats and mice at 22 mg/kg and 42.7 mg/kg, respectively, and loss of righting reflex at 112.8 mg/kg and 160 mg/kg, respectively. Flunarizine is the longest-acting drug and has the slowest onset. At a dose of twice the minimal ED50 flunarizine affords protection against tonic extension of hindpaws in rats (MMS) for 23 h 30 min dephenylhydantoin for 11 h 38 min, phenobarbital for 8 h 22 min and cinnarizine for 8 h 16 min. Peak effect was reached with flunarizine at 5 h 45 min, with diphenylhydantoin at 3 h 38 min, with cinnarizine at 2 h 34 min and with phenobarbital at 1 h 35 min. The anti-MMS profiles of cinnarizine and flunarizine resemble that of dephenylhydantoin as all three compounds are selective blockers of tonic extension of hindpaws. Phenobarbital antagonized the whole MMS-pattern, i.e., tremors, clonic convulsions and tonic extension of fore- and hindpaws. However, the effects of phenobarbital against tremors, clonic convulsions and tonic extension of forepaws may reflect more a general CNS-depressant effect than a specific anticonvulsive activity since neurotoxic effects (ataxia and loss of righting reflex) appear at the same doses.
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PMID:Anticonvulsive properties of cinnarizine and flunarizine in rats and mice. 124 63

Phenobarbital is a long-acting barbiturate often prescribed for seizure disorders. It has a high abuse potential and was commonly used in suicide attempts in the past. Although benzodiazepines are now more frequently used in suicide attempts, barbiturate intoxications are still occasionally seen and constitute a medical emergency. The management of phenobarbital overdose includes cardiac and respiratory support, cathartics, activated charcoal, and alkaline diuresis. In severely compromised patients, hemodialysis and hemoperfusion can be used to enhance drug clearance.
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PMID:Acute phenobarbital intoxication. 150 22

Leukocyte activation is known to involve cell membrane potential changes. Phenobarbital, an anesthetic and anticonvulsant that can inhibit neuronal membrane depolarization, may also affect leukocyte activation. Measuring membrane potential, actin polymerization, chemotaxis, superoxide production, lymphocyte proliferation, intracellular calcium concentration, and cytokine production, we found that phenobarbital at a concentration of 15-30 micrograms/ml, which is considered a therapeutic serum level for controlling seizures, did not affect polymorphonuclear neutrophil (PMN) activation. At levels higher than 100 micrograms/ml, phenobarbital significantly suppressed formylmethionyl-leucyl-phenylalanine (fMLP)-induced chemotaxis. Concentrations greater than 300 micrograms/ml also inhibited phorbol myristate acetate-stimulated membrane potential change. In contrast, 30 micrograms/ml phenobarbital significantly inhibited lymphocyte proliferation stimulated by phytohemagglutinin (PHA) and pokeweed mitogen. This concentration of phenobarbital also suppressed the increase of intracellular free calcium induced by PHA. However, only a higher concentration of phenobarbital (300 micrograms/ml) was able to inhibit PHA-induced interleukin-2 (IL-2) production and suppress the proliferation of PHA-induced IL-2 receptor-bearing lymphocytes. These results suggest that concentrations of phenobarbital associated with anticonvulsive levels do not affect PMN activation but suppress lymphocyte activation, possibly by affecting intracellular signal transduction.
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PMID:Effects of phenobarbital on leukocyte activation: membrane potential, actin polymerization, chemotaxis, respiratory burst, cytokine production, and lymphocyte proliferation. 150 69

The K+ channel blocker 4-aminopyridine (4-AP) causes epileptiform activity in in vitro preparations and is a potent convulsant in animals and man. In mice, 4-AP produces behavioral activation, clonic limb movements and wild running, followed by tonic hindlimb extension and death (ED97, 13.3 mg/kg, s.c.). We evaluated the ability of a series of anticonvulsant drugs to protect against 4-AP-induced seizures using lethality as the endpoint. Drugs with a phenytoin-like profile of activity were protective with ED50 values (all in mg/kg, i.p.) of 34.4 for phenytoin, 18.6 for carbamazepine, 26.9 for felbamate, and 41.5 for zonisamide. Phenobarbital and valproate also protected against 4-AP-induced seizures and lethality (ED50s, 30.6 and 301, respectively). In contrast the NMDA antagonists (+/-)-CPP and (+)-MK-801 were inactive as were the GABA enhancers diazepam, vigabatrin and tiagabine; the antiabsence drug ethosuximide; and the L-type Ca2+ channel blocker nimodipine. We conclude that drugs like phenytoin which block seizure spread are effective antagonists of seizures induced by K+ channel blockade. Drugs with specific actions on other cellular targets may be weak or inactive, presumably because they are unable to attenuate the spread of intense (non-NMDA receptor mediated) excitation evoked by 4-AP.
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PMID:Effects of anticonvulsant drugs on 4-aminopyridine-induced seizures in mice. 156 41

Five children with Landau-Kleffner syndrome (epilepsy, acquired aphasia, and continuous spike-wave discharges during sleep), were treated with antiepileptic drugs (AEDs), sleep-modifying drugs, and corticosteroids. The pharmacologic profiles differed from those observed in focal epilepsies, resembling instead those of certain generalized epilepsies, such as West or Lennox-Gastaut syndromes. Phenobarbital (PB), carbamazepine (CBZ), and phenytoin (PHT) were ineffective or worsened the EEG and neuropsychological symptoms, whereas valproate (VPA), ethosuximide (ESM), and benzodiazepines were partially or transiently efficacious. Dextroamphetamine produced a dramatic but transient improvement in waking and sleep EEG in one of two children; aphasia did not change. Corticosteroid treatment resulted in improved speech, suppression of seizures, and normalization of the EEG in three of three children. Our own experience and data from the literature suggest that corticosteroids should be given in high doses as soon as the diagnosis is firmly established and should be continued in maintenance dose for several months or years to avoid escape. Early diagnosis, before mutism or global deterioration develops, appears to be essential for effective therapy with minimal neuropsychological sequelae.
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PMID:Landau-Kleffner syndrome: a pharmacologic study of five cases. 170 Sep 53

Barbiturates retain an important place in clinical neurological practice. They are used as both diagnostic and therapeutic drugs, their most common uses being as anticonvulsant and anaesthetic agents. This article explores the current theories explaining the mechanism of action of the barbiturates, with special emphasis on their anaesthetic and anticonvulsant effects. The primary mechanism of action of barbiturates is to increase inhibition through the gamma-aminobutyric acid (GABA) system. Anaesthetic barbiturates also decrease excitation via a decrease in calcium conductance. Phenobarbital (phenobarbitone), the primary anticonvulsant barbiturate, is effective for partial, complex partial and secondarily generalised seizures. While no longer the drug of choice for all these seizure types, it remains an important and useful agent. Mysoline has been shown to be useful in the treatment of essential tremor and several other movement disorders, and as an anticonvulsant. Barbiturates are also used for their sedative-hypnotic properties. A relatively new use is in the evaluation of patients with medically intractable seizure disorders for possible surgical therapy. The roles of methohexital and amobarbital (amylobarbitone) are discussed in the section on barbiturates used as diagnostic agents. The experimental use of barbiturates is also commented on; the most important of these is perhaps the use of barbiturates in cerebral resuscitation.
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PMID:The clinical use of barbiturates in neurological disorders. 172 Mar 79


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