Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics of antiepileptic drugs used for the treatment of human epilepsies is reviewed for dogs and cats. In dogs, especially phenobarbital and primidone must be regarded as useful drugs for chronic treatment on account of their elimination rate and bioavailability. Phenytoin, carbamazepine, valproic acid and benzodiazepines are eliminated so rapidly that a therapeutic value cannot be expected. In cats, phenytoin, phenobarbital, valproic acid and diazepam must be regarded as suited for chronic treatment, but there is a definite lack of clinical experience. Phenobarbital and primidone are useful for treatment of clonic-tonic generalized seizures (grand mal) in dogs. The effect of primidone depends mostly on its metabolite phenobarbital. Since primidone, given in high dosage for longer periods of time, gives rise to liver damage, phenobarbital is regarded as the drug of first choice. A status epilepticus may be treated by i.v. injection of diazepam, clonazepam, phenytoin or lidocaine. In cats with grand mal, treatment with daily doses of about 1 mg/kg diazepam may be tried. It proved effective for longer time periods without development of tolerance. There is no reliable clinical experience with other drugs in this species.
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PMID:[Pharmacologic principles in the treatment of epilepsy in the dog and cat]. 383 46

The in vivo effects of phenytoin (diphenylhydantoin, Dilantin) and the experimental anticonvulsant, eboracin, a substituted indenopyrrole, were compared in mice. Pretreatment with varying dosages of either agent followed by challenge with the chemoconvulsant pentylenetetrazol (Metrazol) indicated that eboracin provided slightly less protection against seizures than phenytoin and was much less toxic. Intermediate doses of either agent led to a form of clonic status epilepticus which persisted for an average of 18 min in phenytoin-treated and 58 min in eboracin-treated mice. Pretreatment with higher or lower doses did not lead to these manifestations. Animals in which this syndrome had been induced should be of value in studies of the chemistry and physiology of the clonic state.
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PMID:Comparison of anticonvulsive properties of eboracin and phenytoin in mice. 397 47

Cerebellar and cerebral neocortical explants were exposed to concentrations of phenytoin (DPH) ranging from 2 to 22.5 micrograms/ml of buffered balanced salt solution while extracellular electrical activity was recorded. DPH applied to cerebellar cultures produced a biphasic effect on cortical spontaneous activity, with an initial excitatory phase followed by more sustained suppression. The duration of each of these phases was dose dependent. A similar biphasic effect of DPH on stimulus-elicited responses in cultures of cerebral neocortex was noted. An enhancement of the amplitudes of these responses and prolonged oscillatory afterdischarges were early consequences of DPH application. After variable intervals up to 1/2 hour later, there was a prolonged attenuation of these responses. The initial excitatory effect of DPH demonstrated upon direct application to neurons in culture raises the possibility that intravenous DPH may not be the most appropriate drug for the rapid treatment of status epilepticus in man.
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PMID:Biphasic electrophysiological effects of phenytoin on neural tissue cultures. 631 8

Current trends and controversies in the antiepileptic drug therapy are reviewed from a clinical view. The usefulness of prophylactic therapy of febrile seizures and posttraumatic seizures or posttraumatic epilepsy is compromised by difficulties in the management of the patients especially by noncompliance. Previously untreated epilepsies can be treated successfully in 70--80% of the patients. Phenytoin or carbamazepine are equally effective for generalized tonic-clonic seizures of focal seizures, while absence seizures are controlled by ethosuximide or valproic acid. Only when the epilepsy is uncontrolled despite high plasma concentrations which cannot be raised because of side effects, a second drug should be given. A second drug is successful in about one out of six patients with focal epilepsy. Phenytoin, carbamazepine, phenobarbital and primidone seem to be equally effective for these drug-resistant cases. Status epilepticus can be treated with intravenous diazepam or phenytoin and, if necessary, with an infusion of phenytoin. Rectal diazepam is useful for acute pediatric therapy. Drugs of second choice are clonazepam, phenobarbital, lidocaine, and clomethiazole. In the pregnant epileptic patient a drop in the plasma concentration of antiepileptic drugs mainly through non-compliance and seizure provocation through sleep deprivation are major sources for the deterioration of epilepsies during pregnancy. The "fetal antiepileptic drug syndrome", malformations and an increased risk for epilepsy in the child are discussed as an interaction of parental epilepsy and drug-exposure during pregnancy. Finally, the interpretation of abnormal clinical chemistry data is reviewed. Disorders of the liver, bone, thyroid gland and blood are rarely seen in treated epileptic patients usually when specific risk factors are present. The over-interpretation of laboratory abnormalities e.g. an isolated increase of gamma-GT may lead to iatrogenic deterioration of epilepsy when the effective dose of the drug is reduced for unfounded fear of hepatic toxicity.
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PMID:[Pharmacotherapy of epilepsy--current problems and controversies]. 641 28

Single-dose intravenous phenytoin (9.4-21.3 mg/kg) effectively eradicated seizures within 3 minutes in 12 out of 13 patients in status epilepticus. Eleven additional patients were treated prophylactically. No adverse effects were observed and neurological status was unaltered in all 24 cases. Phenytoin volume of distribution was found to decline significantly with age from 1.6 L/kg at 1 year to 0.6 at 10 years (P less than 0.01). Estimates of Vmax, the maximal rate of phenytoin metabolism, were obtainable in 8/24 patients and were in the expected range (10.6 +/- 4.2 mg/kg/day) for their age (6.6 +/- 2.8 years). Therapeutic serum concentrations (initial post distribution values 17.9 +/- 9.0 micrograms/ml) were maintained for more than 10 hours in 15/24 patients. Single-dose intravenous phenytoin is both effective and safe in the treatment and prevention of epileptic seizures in pediatric patients.
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PMID:Kinetics of intravenous phenytoin in children. 673 85

Twenty-two patients with partial status epilepticus were treated with phenytoin (DPH) intravenously (mean daily dose: 18,6 +/- 7,3 mg/kg). Benzodiazepines had been administered unsuccessfully in 18 cases before DPH. Seizures were stopped in 14 cases (less than 2 hours after the end of the initial dose in 13 cases). Failures were usually encountered in patients with severe brain damages. Adverse effects were observed in two patients: choreo-athetosic movements in one case with DPH plasma levels lower than 15 mg/l, cerebellar signs in the second patient whose DPH plasma level was 28 mg/l. As previously suggested by Cranford and al., the authors recommend a single slow intravenous infusion of 20 mg/kg (at a rate not exceeding 1 mg/kg/mn). The determination of DPH plasma concentrations demonstrated that with this procedure effective plasma levels are obtained during the 24 hours following the IV injection. In case of failure or of adverse effects determination of DPH plasma levels may be useful for adjusting the daily DPH dose.
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PMID:[Use of intravenous phenytoin in treatment of partial status epilepticus (author's transl)]. 678 3

Five patients who were treated with long-term diphenylhydantoin for epilepsy developed neurological signs of poisoning. In 4 cases the symptoms appeared following treatment of status epilepticus with additional phenytoin medication. All patients had an acute symptomatic psychosis and a diffuse slowing of the curves in the EEG. All 5 patients showed cerebellar signs and two of them complained additionally of objective polyneuropathy, a third case complaining of itching only. An axonal polyneuropathy with minimal reduction in motor nerve conduction and a considerable extension of distal latency and diminution of compound action potential was found. In one case the biopsy showed concentric lamellar bodies coming from the axon, with intact myelin sheaths. All alterations were reversible. The pathogenesis of toxicity is discussed. Cumulation of toxic products in the plasma arising from delayed elimination of DPH metabolites is pointed out. However, one case with cerebellar signs had normal DPH levels.
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PMID:[Neurological signs in diphenylhydantoin intoxication (case reports and review) (author's transl)]. 725 13

Seizures are commonly encountered in patients who do not have epilepsy. Factors that may provoke such seizures include organ failure, electrolyte imbalance, medication and medication withdrawal, and hypersensitive encephalopathy. There is usually one underlying cause, which may be reversible in some patients. A full assessment should be done to rule out primary neurological disease. Treatment of seizures in medically ill patients is aimed at correction of the underlying cause with appropriate short-term anticonvulsant medication. Phenytoin is ineffective in the management of seizures secondary to alcohol withdrawal, and in those due to theophylline or isoniazid toxicity. Control of blood pressure is important in patients with renal failure and seizures. Non-convulsive status epilepticus should be considered in any patient with confusion or coma of unclear cause, and electroencephalography should be done at the earliest opportunity. Most ill patients with secondary seizures do not have epilepsy, and this should be explained to patients and their families. Only those patients with recurrent seizures and uncorrectable predisposing factors need long-term treatment with anticonvulsant medication.
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PMID:Medical causes of seizures. 980 2

An animal model of self-sustaining status epilepticus (SSSE) induced in rats by brief intermittent perforant path stimulation (PPS) was examined with regard to the effects of two conventional antiepileptic drugs, diazepam and phenytoin. Thirty or sixty minutes PPS induced SSSE characterized by continuous behavioral and electrographic seizures lasting for hours. Both diazepam (10 mg/kg i. v.) and phenytoin (50 mg/kg i.v.) prevented the establishment of SSSE when administered 10 min prior to PPS. The injection of diazepam to seizing animals, 10 min after the end of 30 min PPS, was significantly less effective than pretreatment in attenuating SSSE. Administration of diazepam after 60 min PPS was characterized by a further decrease of its efficacy. Phenytoin was effective in aborting SSSE when injected 10 min after 30 min PPS. However, its efficacy was vastly decreased if injected 40 min after 30 min PPS, or 10 min after 60 min PPS. It is concluded that antiepileptic drugs, while highly effective in blocking the induction of SSSE, failed to affect its maintenance. SSSE induced by PPS is an advantageous animal model of refractory status epilepticus, which may be used in preclinical studies of novel antiepileptic drugs.
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PMID:Time-dependent decrease in the effectiveness of antiepileptic drugs during the course of self-sustaining status epilepticus. 983

Phenytoin (5,5-diphenylhydantoin), which has been in use for 60 years, is still an important antiepileptic drug. Its primary mechanism of action is modulation of the sustained repetitive firing of neurones by direct inhibition and blockage of voltage-gated sodium channels in the neuronal cell membrane, and by delay of cellular reactivation. The plasma protein binding of phenytoin is normally between 90% and 95%. The drug is rapidly distributed from the blood to the tissues and is almost completely metabolized in the liver. The plasma phenytoin concentration normally reaches the steady-state level within 1-2 weeks. The half-life of phenytoin is less than 20 h in low doses, but is prolonged in high doses, newborn infants and elderly people. The half-life is shortened when phenytoin is given concomitantly with an enzyme-inducing drug, such as phenobarbital or carbamazepine. Phenytoin is effective for treating generalized tonic-clonic seizures, partial seizures with or without generalization, and convulsive status epilepticus. Over the years, many new, and even serious, adverse effects of phenytoin have been recognized. Phenytoin encephalopathy, manifesting as cognitive impairment and a cerebellar syndrome, is an important adverse neurological effect, the development of which depends on the saturation kinetics of phenytoin, individual differences in phenytoin metabolism, an inhibitory effect of certain drugs on phenytoin metabolism, or the ability of certain drugs to displace phenytoin from plasma proteins, leading to an increase in the plasma level of unbound phenytoin. Because of its potentially adverse effects, phenytoin is not recommended as the first choice for treating epileptic seizures, except as a co-drug for managing convulsive status epilepticus. In patients with epilepsy who also have intellectual disability, and are susceptible to balance disturbances and cognitive dysfunction, it is wise to replace phenytoin with another drug, such as carbamazepine or oxcarbazepine. The long-term use of phenytoin is not recommended for patients with loss of locomotion, marked cognitive impairment, or symptoms and signs of cerebellar disease. The prevention of phenytoin intoxication, with the subsequent development of phenytoin-induced encephalopathy, depends on careful observation of the patients and frequent monitoring of plasma levels of phenytoin and other concomitantly administered antiepileptic drugs.
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PMID:Phenytoin: effective but insidious therapy for epilepsy in people with intellectual disability. 1003 Apr 28


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