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

Several new antiepileptic drugs have become available recently. Since seizures and epilepsy are common, primary care physicians are likely to encounter a patient who is taking one of these new medications. Successful medical management of epilepsy requires a proper understanding of medication half-life, indications, and side effects. Felbamate has a broad spectrum of efficacy but is limited by side effects and idiosyncratic reactions. Fosphenytoin has the efficacy of phenytoin and offers the advantage of intramuscular and intravenous dosing without the significant adverse effects associated with intravenous phenytoin; however, it is expensive. Gabapentin has minimal side effects and drug interactions yet has limited efficacy for seizures. Lamotrigine has broad seizure efficacy but requires a slow adjustment to therapeutic levels. Topiramate has minimal drug interactions, but therapy must be initiated slowly to avoid side effects. All of the new antiepileptics hold great promise in the management of patients with recurrent seizures.
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PMID:New antiepileptic drugs. Overcoming the limitations of traditional therapy. 922 84

Twenty-five to 40 percent of patients with epilepsy continue to have seizures despite optimal treatment with traditional antiepileptic drugs. Treatment with standard anticonvulsants such as phenytoin, carbamazepine, valproic acid and phenobarbital is often complicated by side effects and by failure to adequately control seizures. Up to 61 percent of patients with seizures report having side effects with antiepileptic drugs. After a 15-year hiatus since the last new antiepileptic drug was marketed, five new drugs have been approved by the U.S. Food and Drug Administration for the control of seizures. Three of these, gabapentin, lamotrigine and topiramate, are approved for use in adults with partial seizures with or without generalization. Felbamate is approved for the above indication and also for use in children with Lennox-Gastaut syndrome, a rare childhood seizure disorder. Felbamate and lamotrigine have the potential of significant side effects and should be prescribed by physicians experienced in managing patients with complicated epilepsy. Fosphenytoin is a parenteral prodrug of phenytoin that is more tolerable than parenteral phenytoin.
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PMID:Newer antiepileptic drugs: gabapentin, lamotrigine, felbamate, topiramate and fosphenytoin. 947 99

Fosphenytoin, a prodrug of phenytoin, is rapidly and completely converted to phenytoin in adults after intravenous or intramuscular administration and is significantly better tolerated than parenteral phenytoin. Fosphenytoin is highly plasma-protein bound and, when present in sufficient concentration, will displace phenytoin from plasma proteins. The clinical utility is that fosphenytoin may be used to achieve therapeutic phenytoin concentrations more rapidly than intravenous phenytoin infused at its maximum recommended rate. In a clinical study of generalized convulsive status epilepticus, fosphenytoin, with or without benzodiazepine pretreatment, controlled seizures in 76 (93.8%) of 81 patients. In other studies, fosphenytoin maintained seizure control when substituted for oral phenytoin and for seizure prophylaxis in neurosurgery and trauma patients. Adverse events associated with fosphenytoin generally were related to the central nervous system and were similar to those associated with phenytoin, except for a higher incidence of transient pruritus with fosphenytoin. Intravenous fosphenytoin has significant advantages over intravenous phenytoin: It requires a shorter infusion time and fewer intravenous disruptions, causes less pain and burning at the infusion site and minimal consequences in case of intravenous infiltration, allows longer maintenance of intravenous sites, and has better intravenous fluid compatibility and stability. In contrast to intramuscular phenytoin, intramuscular fosphenytoin is well tolerated in both large loading doses and maintenance doses.
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PMID:Clinical experience with fosphenytoin in adults: pharmacokinetics, safety, and efficacy. 979 47

Two pharmacoeconomic studies on the treatment of acute seizures have been conducted. In 1991, Kriel and colleagues surveyed parents of children with a history of cluster seizures, prolonged seizures, or status epilepticus who had been instructed in the use of rectal diazepam. A comparison of data before instruction with data after instruction showed a reduced need for emergency department visits with rectal diazepam. Instruction thus provided a pharmacoeconomic benefit, despite the cost of the product. In 1996, Marchetti and coworkers found that intravenous fosphenytoin was associated with fewer adverse events than intravenous phenytoin. Fosphenytoin thus reduced the need for adverse event management and provided a substantial pharmacoeconomic benefit, despite its higher cost, compared with phenytoin. This study had a number of limitations, however, and hospital pharmacists remain resistant to the use of fosphenytoin. Additional studies may provide more pharmacoeconomic data to support the greater use of fosphenytoin in the treatment of acute pediatric seizures.
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PMID:Pharmacoeconomic considerations in treatment options for acute seizures. 979 50

Advantages and disadvantages of Fosphenytoin. Advantages. More rapid intravenous administration than phenytoin and no need for an in-line filter. May be administered by intramuscular injection. Lower potential for local tissue and cardiac toxicity than phenytoin. Associated with less pain and phlebitis at the injection site, fewer reductions in infusion rate and fewer changes of administration site because of injection site complications than phenytoin. Benefits in terms of ease of administration and improved tolerability vs phenytoin have pharmacoeconomic implications which may translate into an overall cost advantage. Disadvantages. Approximately 10-fold higher acquisition cost vs phenytoin. Fosphenytoin is a parenterally administered prodrug of phenytoin, used in the treatment of patients with seizures. Advantages of fosphenytoin over phenytoin include more rapid intravenous administration, no need for an intravenous filter, and a lower potential for local tissue and cardiac toxicity. Unlike phenytoin, fosphenytoin may also be administered by intramuscular injection. Pharmacoeconomic data from a small study of patients with acute seizures in a US emergency department showed an overall cost advantage of fosphenytoin over phenytoin, despite a considerably greater acquisition cost of fosphenytoin. The main cost drivers for phenytoin therapy were treatment costs associated with adverse events. In view of the limited pharmacoeconomic data currently available, it is in the interests of individual institutions to conduct their own formal pharmacoeconomic studies applying local cost data and patterns of clinical practise to determine whether fosphenytoin should replace phenytoin on their formularly list.
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PMID:Fosphenytoin. Pharmacoeconomic implications of therapy. 1034 19

An acute toxic interaction has been described, in which sublethal doses of pyridostigmine bromide (PB) and the insect repellent N,N-diethyl-m-toluamide (DEET), when administered concomitantly, resulted in seizures and lethality. To investigate the possible relationships between seizures and lethality and the role of the cholinergic system in this interaction, PB (5 mg/kg), DEET (200 mg/kg) or PB (3 mg/kg) + DEET (200 mg/kg) were administered i.p. to male ICR mice, alone or following i.p. pretreatment, with one of several anticonvulsant agents: diazepam, 10 mg/kg; fosphenytoin, 40 mg/kg; phenobarbital, 45 mg/kg; or dextrophan, 25 mg/kg), or the anticholinergic agents, atropine (5 mg/kg), atropine methyl nitrate (2.7 mg/kg), or mecamylamine (2.5 mg/kg). The anticonvulsants selected for this study act through different mechanisms to reduce seizures. None of the anticonvulsants was able to reduce the incidence of seizures following treatment with PB, DEET or PB + DEET. Only diazepam delayed the onset of seizures. Fosphenytoin or diazepam significantly prolonged the time to lethality following PB, but only fosphenytoin reduced the incidence of PB-induced lethality. Diazepam or phenobarbital significantly prolonged the time to lethality following PB + DEET. Both atropine and atropine methyl nitrate protected against PB and PB + DEET-induced lethality and PB-induced seizures. Neither agent blocked seizures resulting from DEET or PB + DEET. Mecamylamine reduced seizures and lethality in PB-treated mice, but not in mice treated with DEET or PB + DEET. The results indicate that seizure activity is not a causative factor in the toxic interaction between PB and DEET. Furthermore, PB, DEET and PB + DEET induce seizures that are resistant to standard anticonvulsants, and each appears to operate through different mechanisms to produce seizures. Peripheral muscarinic receptors may play a specific role in lethality caused by PB + DEET.
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PMID:Anticonvulsant-resistant seizures following pyridostigmine bromide (PB) and N,N-diethyl-m-toluamide (DEET). 1041 76

Status epilepticus (SE) treatment should proceed on four fronts: termination of SE, prevention of recurrence, management of potential precipitating causes, and management of SE complications and underlying conditions. The intensity of the treatment should reflect the risk to the patient from SE, and drugs likely to depress respiration and blood pressure should initially be avoided. The Veterans Administration cooperative trial showed that when treating overt SE, first-line treatment success rates were: lorazepam 64.9%; phenobarbital 58.2%; diazepam/phenytoin 55.8%; and phenytoin alone 43.6%. The aggregate response rate to second-line agents for patients who did not respond to first-line agents was 7.0%, and it was 2.3% for third-line agents, raising the question of the efficacy of a second and third drug. The recommended treatment for generalized convulsive SE is to begin with lorazepam. As a second-line agent, phenytoin or fosphenytoin, is still recommended if SE control is not achieved within 5 to 7 min. Fosphenytoin achieves a free phenytoin level of about 2 micro/mL in 15 min, as opposed to 25 min with phenytoin itself. Moreover, fosphenytoin is safer and, despite higher cost, it may be cost-effective. High-dose barbiturates, high-dose benzodiazepines, and propofol are employed for major treatment for refractory SE. Patients at this stage should undergo continuous electroencephalogram monitoring. Once SE is controlled, prevention of seizure recurrence should be individualized to each patient. The major complications of generalized convulsive SE (GCSE), rhabdomyolysis and hyperthermia, should be watched for and treated.
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PMID:Management approaches to prolonged seizures and status epilepticus. 1042 62

If continuous seizure activity lasts longer than 5 minutes generalized tonic-clonic seizures require prompt treatment, if significant morbidity and mortality are to be avoided. The mortality varies (mean: 20%) depending on patient age and etiology. Control of status epilepticus is achieved by benzodiazepines in about 80% of cases: Lorazepam is recommended due to its longer-acting effects on the central nervous system. To maintain the anticonvulsive effect phenytoin is usually administered intravenously. Fosphenytoin (not approved in Germany) has advantages over phenytoin, because it can be given three times more rapidly and produces fewer side effects. The IV use of valproic acid in status epilepticus seems to be promising, but needs further evaluation. There is no generally accepted treatment protocol for the therapy of persistent seizure activity lasting more than 60 minutes (i.e., refractory status epilepticus). Usually phenobarbital, or general anesthesia with thiopental or pentobarbital are treatment recommendations. In recent reports, the administration of midazolam or propofol proved to be effective and well-tolerated.
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PMID:[Therapy of generalized tonic-clonic status epilepticus in adulthood]. 1070 6

Tonic-clonic status epilepticus (TCSE) is the most common neurological emergency and affects approximately 60000 patients each year in the US. The risk of complications increases substantially as TCSE lasts longer than 60 minutes. Ideally, drugs used to treat this condition should be well tolerated when administered as rapid intravenous infusions and should not interfere with patients' state of consciousness or cardiovascular and respiratory functions. Because of its efficacy, absence of sedation or respiratory suppression, intravenous phenytoin has largely replaced phenobarbital (phenobarbitone) as the second agent of choice (following the administration of a benzodiazepine) in the treatment of TCSE. While the efficacy of phenytoin in the treatment of acute seizures and TCSE is well established, the parenteral formulation of phenytoin has several inherent shortcomings which compromise its tolerability and limit the rate of administration. Intravenous phenytoin has been associated with fatal haemodynamic complications and serious reactions at the injection site including skin necrosis and amputation of extremities. Fosphenytoin, a phenytoin prodrug, has the same pharmacological properties as phenytoin but none of the injection site and cardiac rhythm complications of intravenous infusions of phenytoin. While fosphenytoin costs more than intravenous phenytoin, treating the acute and chronic complications of TCSE itself, and the complications of intravenous phenytoin can also be costly. All other factors being equal, there is no doubt that fosphenytoin is better tolerated and can be delivered faster than intravenous phenytoin; 2 measures that clearly improve outcome in patients with TCSE. The tolerability of intramuscular fosphenytoin also extends its use to clinical situations where prompt administration of a nondepressing anticonvulsant is indicated but secure intravenous access and cardiac monitoring are not available, such as treatment of seizures by rescue squads in the field and serial seizures in the institutionalised, elderly and other patients with intractable epilepsy.
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PMID:Fosphenytoin and phenytoin in patients with status epilepticus: improved tolerability versus increased costs. 1087 39

The advent of numerous new treatment options in epilepsy therapy over the last decade is enabling a more flexible and individualized approach to patients with seizures. For some patients, these products offer added efficacy, reduction of troublesome side effects associated with standard anticonvulsants, and control over acute seizure exacerbations. This review profiles new formulations of anti-epileptic drugs. Tegretol-XR (TXR) and Carbatrol (CBTL), two extended-release preparations of carbamazepine (CBZ), which allow twice daily administration, minimising drug toxicity and improving efficacy. Topiramate sprinkles and lamotrigine chewable dispersible tablets allow easier administration in children. The rectal gel preparation of diazepam (Diastat) is useful for parents of patients with acute seizure exacerbations. Intravenous valproate (Depacon) and fosphenytoin (Cerebyx) provide parenteral treatment of acute seizures, without sedation or significant peripheral venous side effects. All of these new formulations expand treatment options for patients with epilepsy, who will benefit from them.
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PMID:New formulations of drugs in epilepsy. 1124 64


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