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

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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Intramuscular use of fosphenytoin: an overview. 864 11

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.
 ...
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.
 ...
PMID:Recent advances in the pharmacotherapy of epilepsy. 922 Feb 4

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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Pharmacoeconomic considerations in treatment options for acute seizures. 979 50


1 2 3 Next >>