Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum levels of mephenytoin (Mesantoin) and its metabolite nirvanol were correlated with effectiveness and side effects in 93 patients. Mean mephenytoin level was 8% of the combined mephenytoin plus nirvanol levels. "Total mephenytoin" level should be used clinically, as neither individual component is as well correlated with clinical phenomena. Serum levels of 25 to 40 mug/ml usually yield improvement in seizure control without discomfort, and three-quarters of patients had fewer seizures. Side effects frequently associated with phenytoin were absent, but drowsiness, an occasional rash, and a single, fatal case of aplastic anemia were found. Performance on psychological tests of cognitive-attentional skills showed a modest improvement during mephenytoin administration. The drug merits wider employment in refractory seizure problems, but vigilant follow-up is required.
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PMID:Mephenytoin: a reappraisal. 100 Dec 84

Plasma phenytoin levels were measured in 60 patients under steady-state conditions for a period of six weeks. During the trial, the preparation of phenytoin was changed from Phenytoin BP (Regent) to Epanutin Infatabs. A significant increase in plasma phenytoin levels following the change of tablet was matched by a decrease in the number of seizures.
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PMID:Bioavailability of phenytoin. A comparison of two preparations. 124 84

In this article the efficacy of carbamazepine for seizure prophylaxis in severe head injuries is tested. In addition, conditions with high risk of seizures requiring prophylactic regimen, were defined. One hundred and thirty-nine patients above 15 years of age with severe head injuries were included in the study. They were randomly divided into two groups--carbamazepine versus placebo. Prophylaxis was started immediately after the accident and was continued for one and a half to two years. Carbamazepine dosage was adjusted individually to provide serum levels within therapeutic range. In case of a seizure all the necessary clinical management was initiated. Patients on carbamazepine showed a lower probability of post-traumatic seizures than those on placebo (p less than 0.05). This difference was statistically significant with regard to early seizures within the first week and with regard to the follow-up time in total, but not regarding late seizures per se. Brain lesions with a high risk of post-traumatic seizures were situated in the parietal and temporal areas and included acute subdural haematomas in all locations, temporal lobe contusions, parietal epidural haematomas accompanied by other lesions and the deep stages of coma. Brain stem contusions were accompanied by a rather low probability of seizures. The above mentioned types and locations of brain lesions with the exception of brain stem contusions justify antiepileptic prophylaxis. The regimen consists of oral carbamazepine 100 mg three times daily by gastric tube during the first two days increasing to about 200 mg three times daily on the third day corresponding to the serum level. If oral medication is not possible within the initial twelve hours, phenytoin in a dose of 750 mg Phenhydan-Infusion Konzentrate is given on the first day, followed by an intravenous dose of 250-500 mg on the second day or until oral carbamazepine administration is tolerated. Treatment should be continued for one year.
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PMID:[Seizure prevention using carbamazepine following severe brain injuries]. 641 Feb 92

In the past decade, several new antiepileptic drugs have been tested. Most recently, 5 new antiepileptic drugs have been launched onto European and US markets. These include vigabatrin, oxcarbazepine and lamotrigine in Europe, and felbamate and gabapentin in the US. In addition to these, 3 additional drugs are in the clinical investigational stage: flunarizine, fosphenytoin and stiripentol. A fourth agent is midazolam, which was originally introduced in 1986, but recently has shown effectiveness in the treatment of status epilepticus. Flunarizine is a selective calcium channel blocker that has shown anticonvulsant properties in both animal and human studies. It is a long-acting anticonvulsant that clinical studies have shown to have effects similar to those of phenytoin and carbamazepine in the treatment of partial, complex partial and generalised seizures. Fosphenytoin was developed to eliminate the poor aqueous solubility and irritant properties of intravenous phenytoin. It is rapidly converted to phenytoin after intravenous or intramuscular administration. In clinical studies, this prodrug showed minimal evidence of adverse events and no serious cardiovascular or respiratory adverse reactions. It may have a clear advantage over the present parenteral formulation of phenytoin. Midazolam is a benzodiazepine that is more potent than diazepam as a sedative, muscle relaxant and in its influence on electroencephalographic measures. It has been shown to be an effective treatment for refractory seizures in status epilepticus. Stiripentol has anticonvulsant properties as well as the ability to inhibit the cytochrome P450 system. There are significant metabolic drug interactions between stiripentol and phenytoin, carbamazepine and phenobarbital (phenobarbitone). Stiripentol has been studied in patients with partial seizures, refractory epilepsy and refractory absence seizures with some efficacious results.
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PMID:New anticonvulsant drugs. Focus on flunarizine, fosphenytoin, midazolam and stiripentol. 752 21

Phenytoin is widely used for the prevention and treatment of acute seizures in children. Although it has the advantage of being available in parenteral form, it cannot be given through the i.m. route. Furthermore, problems with venous accessibility and maintenance may complicate i.v. administration of phenytoin in newborns and very sick infants. Fosphenytoin, a new phenytoin prodrug, can be safely administered through the i.m. route, and, because of the physical characteristics of its formulation, it offers advantages over phenytoin for i.v. administration. Clinical studies with i.v. and i.m. fosphenytoin demonstrate that the efficacy, safety, and pharmacokinetics of this drug are similar in 5- to 18-year-old children and in young adults. The safety and pharmacokinetic profile of i.v. and i.m. fosphenytoin in younger children and infants is currently being investigated.
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PMID:Fosphenytoin use in children. 864 8

Fosphenytoin is a water-soluble disodium phosphate ester of phenytoin that is converted in plasma to phenytoin. Fosphenytoin is compatible with most common i.v. solutions and can be administered safely through the i.m.route. An additional safety factor is the absence of propylene glycol in the fosphenytoin formulation. Propylene glycol is used as a vehicle in the i.v. phenytoin preparation and by itself may produce serious cardiovascular complications. Studies of the pharmacokinetics, safety, and tolerance of i.v. fosphenytoin have demonstrated that fosphenytoin produces phenytoin plasma concentrations similar to those achieved with oral and i.v. phenytoin, but without significant cardiovascular effects and only minimal discomfort at the injection site. Aside from local reactions, the most common adverse events associated with fosphenytoin have been pruritus and reactions typical of phenytoin (e.g., dizziness, somnolence, and ataxia). Fosphenytoin represents a significant advance in the treatment of patients with seizures who require parenteral therapy.
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PMID:Intravenous administration of fosphenytoin: options for the management of seizures. 864 9

Phenobarbital, diazepam, lorazepam, and phenytoin are all currently used for the treatment of acute seizures, including status epilepticus. None of these drugs is considered ideal. Fosphenytoin is a new phenytoin prodrug that fulfills many of the properties of an ideal anticonvulsant drug. The safety, tolerance, and pharmacokinetics of intramuscularly administered fosphenytoin have been evaluated in three clinical trials involving patients requiring loading or maintenance doses of phenytoin. These investigations demonstrated that fosphenytoin is rapidly and completely absorbed after injection into muscle and is quickly converted to produce therapeutic phenytoin plasma concentrations within 30 min of administration. Plasma concentrations of phenytoin achieved with i.m. fosphenytoin exceeded those associated with an equimolar dose of oral phenytoin. i.m. fosphenytoin was well tolerated both locally and systemically. Only mild and transient reactions occurred at the injection site. The most common systemic adverse events reported--somnolence, nystagmus, dizziness, and ataxia--are side effects commonly seen with phenytoin and tended to be mild. Preexisting seizure disorders remained stable. Combination treatment with i.v. diazepam or lorazepam to attain rapid seizure control and i.m. fosphenytoin to maintain the anticonvulsant effect theoretically offers many advantages for control of acute seizures and should be studied.
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PMID:Intramuscular use of fosphenytoin: an overview. 864 11

The cost of emergency department services has become a major concern for patients, providers, and payers. Solid economic information is needed to provide a rationale for the selection of therapeutic options and the provision of care that is both clinically and financially prudent. To assess the full cost of care for patients with seizures who are treated in an acute care setting, a modified activity-based cost-accounting model was developed. The model was populated with data from a double-masked, parallel-group, single-dose, multicenter clinical trial designed to investigate the safety and tolerability of phenytoin (Dilantin) and fosphenytoin (Cerebyx) given intravenously in equivalent loading doses according to established recommendations. A total of 52 patients were enrolled in the trial; 13 were given phenytoin and 39 were given fosphenytoin. Salaries and benefits of emergency medical services personnel, drug acquisition costs, and direct and indirect overhead expenditures common to a large hospital emergency department comprised the total costs to treat enrolled patients and manage adverse events. The average cost to treat patients with fosphenytoin was lower than the cost to treat similar patients with phenytoin based on the frequency of adverse events associated with each comparator and the resources (human and material) consumed in the management of those events.
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PMID:A pharmacoeconomic evaluation of intravenous fosphenytoin (Cerebyx) versus intravenous phenytoin (Dilantin) in hospital emergency departments. 893 Apr 34

Several new agents have recently become available for the long-term treatment of epilepsy. Until now, there has been little change for the acute management of seizures. Three new agents may alter our present practice. Fosphenytoin has recently been approved as a substitute for parenteral phenytoin. It provides similar efficacy without the risk for infusion site injury while allowing greater flexibility in intravenous solutions. Intravenous valproate adds flexibility for patients on valproate, allowing patients to be rapidly loaded. In addition, it will prevent patients from having to change seizure medications when intervening medical illness or surgery do not allow medications by mouth. Viscous diazepam solution for rectal administration will allow for safe and effective treatment for seizures at home and will potentially decrease emergency department services and hospitalization.
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PMID:New drug therapy for acute seizure management. 909 67

The therapeutic options for the treatment of epilepsy have expanded during the 1990s. Since 1993, four novel agents (felbamate, gabapentin, lamotrigine, and topiramate) have been approved by the US Food and Drug Administration, primarily for adjunctive treatment of partial seizures. In addition, a water-soluble pro-drug of phenytoin, fosphenytoin, and a sustained-release preparation of carbamazepine have been introduced. The novel anticonvulsants represent a potential improvement for patients whose seizures are incompletely controlled or who experience significant adverse effects with older anticonvulsants. Felbamate, lamotrigine, and topiramate appear to have a broad spectrum of action in seizure control, but felbamate use is limited by the potential for serious adverse effects. Gabapentin, lamotrigine, and topiramate are all well tolerated. Gabapentin has no known drug interactions, whereas lamotrigine and topiramate have limited interactions compared with older agents. The sustained-release preparation of carbamazepine may decrease the incidence of adverse effects and increase patient compliance. Fosphenytoin offers a safer method for intravenous administration of phenytoin and the added flexibility of intramuscular administration. Taken together, these recent advances in treatment may bring about improved efficacy and decreased adverse effects for many patients with epilepsy.
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PMID:Recent advances in the pharmacotherapy of epilepsy. 922 Feb 4


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