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)

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

Fosphenytoin is a phosphate ester prodrug of phenytoin developed as a replacement for standard injectable sodium phenytoin. After absorption, phenytoin is cleaved (conversion half-life 8-15 min) from fosphenytoin. Unlike phenytoin, fosphenytoin is freely soluble in aqueous solutions (including standard intravenous solutions) and rapidly absorbed by the intramuscular route. Fosphenytoin has been tested successfully for three indications in humans: intramuscular maintenance dosing, intramuscular loading dose administration, and intravenous treatment of status epilepticus. Local toxicity (pain, burning, itching) is less by the intramuscular or intravenous route for fosphenytoin than for standard injectable sodium phenytoin. Systemic toxicity is similar with both preparations except that hypotension is less common and paresthesias are more common with fosphenytoin.
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PMID:Fosphenytoin (Cerebyx). 903 68

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

Fosphenytoin is a phosphate ester prodrug developed as an alternative to intravenous phenytoin for acute treatment of seizures. Advantages include more convenient and rapid intravenous administration, availability for intramuscular injection, and low potential for adverse local reactions at injection sites. Drawbacks include the occurrence of transient paraesthesias and pruritus at rapid infusion rates, and cost. Fosphenytoin is highly bound (93-98%) to plasma proteins. Saturable binding at higher plasma concentrations accounts for an increase in its distribution volume and clearance with increasing dose and infusion rate. Fosphenytoin is entirely eliminated through metabolism to phenytoin by blood and tissue phosphatases. The bioavailability of the derived phenytoin relative to intravenous phenytoin is approximately 100% following intravenous or intramuscular administration. The half-life for conversion of fosphenytoin to phenytoin ranges from 7-15 minutes. Faster intravenous infusion rates and competitive displacement of derived phenytoin from plasma protein binding sites by fosphenytoin compensate for the expected conversion-related delay in appearance of phenytoin in the plasma. Unbound phenytoin plasma concentrations achieved with intravenous fosphenytoin loading doses of 100-150 or 50-100mg phenytoin sodium equivalents/min are comparable, and achieved at similar times, to those with equimolar doses of intravenous phenytoin at 50 (maximum recommended rate) or 20-40 mg/min, respectively. The rapid achievement of effective concentrations permits the use of fosphenytoin in emergency situations, such as status epilepticus. Following intramuscular administration, therapeutic phenytoin plasma concentrations are observed within 30 minutes and maximum plasma concentrations occur at approximately 30 minutes for fosphenytoin and at 2-4 hours for derived phenytoin. Plasma concentration profiles for fosphenytoin and total and unbound phenytoin in infants and children closely approximate those in adults following intravenous or intramuscular fosphenytoin at comparable doses and infusion rates. Earlier and higher unbound phenytoin plasma concentrations, and thus an increase in systemic adverse effects, may occur following intravenous fosphenytoin loading doses in patients with a decreased ability to bind fosphenytoin and phenytoin (renal or hepatic disease, hypoalbuminaemia, the elderly). Close monitoring and reduction in the infusion rate by 25-50% are recommended when intravenous loading doses of fosphenytoin are administered in these patients. The potential exists for clinically significant interactions when fosphenytoin is coadministered with other highly protein bound drugs. The pharmacokinetic properties of fosphenytoin permit the drug to serve as a well tolerated and effective alternative to parenteral phenytoin in the emergency and non-emergency management of acute seizures in children and adults.
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PMID:Fosphenytoin: clinical pharmacokinetics and comparative advantages in the acute treatment of seizures. 1248 78

The characteristic rash of systemic juvenile idiopathic arthritis is a transient erythematous eruption associated with a quotidian spiking fever. Usually asymptomatic, it can be pruritic, with dermatographism at sites of scratching or pressure. An illness similar to this entity in adults is designated adult-onset Still disease. The relationship between the pediatric and adult disease is uncertain and differences in case definition have evolved. Specifically, a sustained arthritis for at least 6 weeks is required for a diagnosis of systemic juvenile idiopathic arthritis, whereas transient arthritis and arthralgia are accepted criteria in adult-onset Still disease. We describe five patients less than 16 years of age who presented with an acute illness characterized by fever and a distinctive skin eruption. Intense pruritus and linear erythematous lesions flared with a spiking fever, usually in the late afternoon and evening. Periorbital edema/erythema and nonlinear urticarial lesions were also seen. Two children had splinter hemorrhages of the nail beds and one girl developed a fixed, scaling, pigmented, linear eruption. Severe malaise, myalgia, arthralgia, and leukocytosis were present in every patient. Other systemic manifestations included sore throat, transient arthritis, abdominal pain, lymphadenopathy, hepatomegaly, splenomegaly, hyperferritinemia, and hepatic dysfunction. No patient had a sustained arthritis. The course of the disease was variable. One patient, diagnosed with macrophage activation syndrome, recovered on oral naproxen. Two patients responded to systemic corticosteroid therapy. One girl developed status epilepticus and died from aspiration and asphyxia. A boy with severe hepatitis developed renal failure and thrombotic thrombocytopenic purpura and was treated with plasmapheresis, dialysis, and systemic corticosteroids; he had recurrent episodes of rash and fever into adult life. These children did not fulfill the case definition of systemic juvenile idiopathic arthritis because they lacked a persistent arthritis. Adolescent and adult patients with the same clinical and laboratory findings are described under the rubric of adult-onset Still disease. Recognition of the distinctive urticarial skin eruption and spiking fever is important in the diagnosis of a disease with severe morbidity and potentially life-threatening complications.
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PMID:A pruritic linear urticarial rash, fever, and systemic inflammatory disease in five adolescents: adult-onset still disease or systemic juvenile idiopathic arthritis sine arthritis? 1546 68

Twenty dogs with confirmed atopic dermatitis were treated with homeopathy. In the first phase of this pilot study, all of the dogs were treated by a veterinary homeopath with individualised remedies prescribed on the basis of the dog's cutaneous signs and constitutional characteristics. The response to treatment was assessed by scoring the severity of pruritus from 0 to 10 on a validated scale. The dogs were evaluated at monthly intervals for at least two months. In 15 cases, the owners reported no improvement following homeopathic treatment. In the other five cases, the owners believed that the homeopathic treatment was associated with a substantial improvement, and reported reductions in pruritus scores ranging from 64 to 100 per cent. These five dogs were selected for the second phase of the study, in which homeopathic remedies were tested against placebos in a randomised and blinded trial. In one of these dogs, atopic dermatitis resolved completely and so this dog could not participate in phase 2; another dog was euthanased because of status epilepticus before phase 2 could be started. In the remaining three cases, the owners correctly distinguished between the placebo and homeopathic remedies, and reported reductions in the pruritus score of 0, 0.2 and 0.8 following placebo treatment and 4.3, 2.4 and 3.0, respectively, following the remedy.
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PMID:Pilot study of the effect of individualised homeopathy on the pruritus associated with atopic dermatitis in dogs. 1944 62

Status epilepticus (SE) and seizure clusters (SC) represent neurologic emergencies with a case fatality rate up to 34%, depending on cause and comorbidity. As SE becomes more refractory to treatment over time, appropriate medication is important. This study aimed to investigate efficacy and tolerability of intravenous (IV) lacosamide (LCM) in treatment of SC and SE. Data of patients with SE or SC who were treated with IV LCM between December 2009 and February 2011 in two Austrian centers were analyzed retrospectively. Clinical information was extracted from patients' charts. Forty-eight patients (26f/22m) aged median 62 years (range 17-95 years) were identified. Thirty-five percent of patients (17 of 48) had SC and 65% (31 of 48) had SE. SE was nonconvulsive in 10 (32%), convulsive in 11 (36%), and focal in 10 (32%) patients. SE was acute symptomatic in six (20%) and remote symptomatic in 11 (35%) patients. Fourteen (45%) had preexisting epilepsy. Median initial bolus dose was 200 mg (range 200-400 mg) in patients with SE and 200 mg in patients with SC. Maximum infusion rate was 60 mg/min. Cessation was observed in 42 patients (88%). Success rate in patients with SE receiving LCM as first or second drug was 100% (8 of 8), as third drug 81% (11 of 15), and as fourth or later drug 75% (6 of 8). There were no side effects observed except for pruritus and skin rash in two patients. These data support use of IV LCM as a potential alternative to standard antiepileptic drugs for acute treatment of seizure emergency situations, although randomized controlled studies are needed.
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PMID:Intravenous lacosamide in status epilepticus and seizure clusters. 2246 73

Status epilepticus is among the most common neurologic emergencies, with a mortality rate of up to 20%. The most important therapeutic goal is fast, effective, and well-tolerated cessation of status epilepticus. Intravenous phenytoin/fosphenytoin, phenobarbital, or valproate is the current standard treatment after failure of benzodiazepines. Lacosamide as a new antiepileptic drug has been available as an intravenous solution since 2009. To date, PubMed lists 19 studies (10 single case reports and 9 case series), reporting a total of 136 episodes of refractory status epilepticus (50% nonconvulsive status epilepticus, 31% focal status epilepticus, and 19% convulsive status epilepticus) treated with lacosamide. The most often used bolus dose was 200-400 mg over 3-5 min. The overall success rate was 56% (76/136). Adverse events (AEs) were reported in 25% (34/136) of patients: mild sedation in 25 cases, 1 patient with possible angioedema, 2 with allergic skin reaction, 4 with hypotension, and 1 with pruritus. One patient developed a third-degree atrioventricular (AV) block and paroxysmal asystole. Overall, the rate of AEs was low. Current evidence on the use of intravenous lacosamide in acute seizures and status epilepticus is restricted to retrospective case reports and case series (class IV). Further prospective studies to inform clinicians are necessary.
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PMID:Lacosamide as a new treatment option in status epilepticus. 2329 81

Fosphenytoin, a water-soluble prodrug of the antiepileptic drug phenytoin, is entirely and rapidly converted to this antiepileptic drug. The mechanism of action of fosphenytoin is related to the blockade of voltage-operated sodium channels. It was developed in order to obtain a phenytoin-like drug with improved water solubility. Its maximal plasma concentration is achieved within 90-190 min following intramuscular administration with bioavailability being complete after intravenous injection. The main indications for fosphenytoin are the treatment of convulsive status epilepticus and the prevention/management of seizures during neurosurgery. Adverse effects of fosphenytoin may include: cardiovascular events (hypotension, arrhythmias), paresthesias or pruritus or some central events - somnolence, headache, dizziness, nystagmus and ataxia. The incidence of purple glove syndrome (edema, discoloration and pain distal to the site of intravenous administration) is less frequent than after phenytoin. Generally, the development of fosphenytoin aimed at avoiding complications associated with parenteral use of phenytoin.
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PMID:The safety and efficacy of fosphenytoin for the treatment of status epilepticus. 2628 87