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)

Changing attitudes towards the use of antiepileptic drugs have led to an emphasis on monotherapy with serum concentration measurement coupled with standard, weight-adjusted starting and maintenance regimens to guide initial therapy and subsequent dosage titration. Currently, the established anticonvulsants are carbamazepine, valproic acid (sodium valproate) and phenytoin. Phenobarbital is now less commonly prescribed due to its propensity to produce sedation and impair cognitive function. The value of pharmacokinetic optimisation with valproic acid is limited by its wide therapeutic index, large fluctuations in the concentration-time profile and concentration-dependent protein binding. Thus, although serum concentrations are often measured, they are rarely subjected to pharmacokinetic interpretation. Carbamazepine has a flatter concentration-time profile than valproic acid. Its target range is more clearly defined and it undergoes autoinduction of metabolism and interacts with other drugs. Pharmacokinetic principles can, therefore, be more readily applied to carbamazepine, although, in general, a simple clinical approach to its use is usually satisfactory. Phenytoin has required the greatest pharmacokinetic input due to its nonlinear pharmacokinetics and narrow target range. Many different graphical methods, equations and computer programs have been reported, some of which demand 2 steady-state, dose-concentration pairs; others function satisfactorily with only 1. Recent attempts have been made to interpret non-steady-state data. In addition, a number of workers have demonstrated the value of altering the population parameter estimates to account for ethnic differences. A pharmacokinetic approach can also be used to tailor the use of phenytoin in the treatment of status epilepticus. Dosage alterations may be needed for specific patient groups. In particular, children generally require higher dosages on a weight-for-weight basis than adults, while equivalently lower dosages should be given to neonates. Most anticonvulsants are principally cleared by hepatic mechanisms, so dosage adjustment is not usually required in renal disease, although care must be taken in interpreting serum concentrations because of changes in protein binding. Close monitoring is required in the elderly and patients with hepatic impairment, while increased dosages may be needed in critically ill patients and during pregnancy. Pharmacokinetic principles can be used in the treatment of treat self-poisoning with anticonvulsants. There are few data available on the pharmacokinetics of vigabatrin, lamotrigine, oxcarbazepine and gabapentin in patients. Due to its mode of action in binding irreversibly to its target enzyme, serum concentration monitoring of vigabatrin plays no role in optimising therapy. The value of applying pharmacokinetic principles with the other 3 drugs remains to be investigated.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacokinetic optimisation of anticonvulsant therapy. 151 37

The relative bioavailability of an investigational carbamazepine suspension was studied following rectal administration in human volunteers. Carbamazepine, in doses of approximately 6 mg/kg, was given to nine men. The routes of administration were oral tablet, oral suspension, and rectal suspension. There was no significant difference (p greater than 0.05) in total absorption, maximum serum concentration, and time to achieve maximum serum concentration between the orally-administered tablet and the rectally administered suspension. Orally administered suspension was absorbed more quickly and completely. All volunteers complained of a strong defecatory urge after the suspension was given rectally. The slow absorption after rectal administration precludes the use of this route in status epilepticus; however, it may be a satisfactory alternative for maintenance therapy when administration by the oral route is not possible.
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PMID:Relative bioavailability of rectally administered carbamazepine suspension in humans. 404 11

The mentally retarded often need concomitant antiepileptic and neuroleptic drug treatment. High doses of neuroleptic drugs may provoke seizures. Antiepileptic drugs may aggravate behavioural problems. The mutual influence of neuroleptic and antiepileptic drug treatment and the effect of seizure control were studied in 20 mentally retarded patients between 1980 and 1989. The treatment was tailored individually, aiming at the lowest effective dose. Carbamazepine was preferred to phenobarbital and phenytoin. The mean defined daily dose (DDD) of neuroleptics and antiepileptics was reduced by 64% and 5%, respectively. Changing the mean DDD of neuroleptics neither correlated significantly with seizure activity nor with the change of the mean DDD of the antiepileptics. Evidently, seizure control may be improved by small neuroleptic doses in some patients. In one patient, however, a non-convulsive status epilepticus was associated with the introduction of neuroleptics. The assumption that carbamazepine has a beneficial effect on behavioural problems was not supported. Apparently, changing the regime of antiepileptics contributed to less neuroleptic requirements, possibly through reduced side-effects and/or improved seizure control. When combining neuroleptics and antiepileptics, interactions should always be considered. The epileptogenic effect of small to standard doses of neuroleptic drugs should, however, not be overemphasized.
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PMID:Neuroleptic and antiepileptic treatment in the mentally retarded. 790 68

The major established drugs used in the management of epilepsy are carbamazepine, valproic acid, phenytoin, phenobarbital, primidone, ethosuximide and benzodiazepine drugs. Carbamazepine and phenytoin are used mainly in the treatment of partial seizures and primarily or secondarily generalized tonic-clonic seizures. Valproic acid is effective against all types of seizures, but it is used most extensively in the management of generalized epilepsies. Ethosuximide is effective against absence seizures. Phenobarbital and primidone are effective against all types of seizures (except for absences) although they are less commonly used because of their sedative properties and adverse effects on cognition. Benzodiazepines are most valuable in the treatment of status epilepticus, but their long-term use is often associated with undesirable sedation and development of tolerance to their antiepileptic effect. Irrespective of the drug used, optimal clinical management requires individualization of dosage and dosing schedules based on careful evaluation of clinical response and sound knowledge of the pharmacokinetics and interaction potential of the individual compounds. Monitoring serum drug concentrations may provide a useful guide to dosage adjustments, particularly in the case of phenytoin, which shows dose-dependent kinetics within the therapeutic dosage range.
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PMID:Established antiepileptic drugs. 906 76

The scorpion venom peptide toxins tityustoxin-K(alpha) (TsTx-K(alpha)) and pandinustoxin-K(alpha) (PiTx-K(alpha)) are novel, highly potent and selective blockers of voltage-activated K+ channels. PiTx-K(alpha) preferentially blocks rapidly inactivating (A-type) K+ channels whereas TsTx-K(alpha) is selective for slowly inactivating (delayed rectifier-type) channels. K+ channel blockers are known to induce seizures, but the specific K channel types that can serve as convulsant targets are not well defined. To address this issue, we examined for convulsant activity the K+ channel type-specific scorpion toxins and the selective K+ channel antagonists 4-aminopyridine (4-AP), an inhibitor of A-type voltage-activated K+ channels, and paxilline, a selective blocker of large conductance (maxi K) Ca(2+)-activated K+ channels. Intracerebroventricular injection of recombinant TsTx-K(alpha) and PiTx-K(alpha) in mice produced limbic and clonic-tonic seizures. The severity of the seizures increased during the 60-min period following injection, culminating in continuous clonic seizure activity (status epilepticus), tonic hindlimb extension, and eventually in death. The estimated doses producing limbic and clonic seizures in 50% of animals (CD50) for TsTx-K(alpha) and PiTx-K(alpha) were 9 and 33 ng, respectively. 4-AP produced seizure activity similar to the toxins (CD50, 76 ng) whereas paxilline failed to induce seizures at doses up to 13.5 microg. Carbamazepine protected fully against the toxin- and 4-AP-induced seizures whereas phenytoin had variable activity against the clonic component although it was protective against tonic hindlimb extension. The AMPA receptor antagonist GYKI 52466 also conferred full protection against toxin-induced seizures, but the NMDA receptor antagonists (R)-CPP and dizocilpine failed to affect limbic and clonic seizures, although they protected against hindlimb extension. We conclude that selective blockade of delayed rectifier- or A-type voltage-activated K+ channels can produce limbic, clonic and tonic seizures, whereas blockade of maxi K-type Ca(2+)-activated K+ channels does not. The convulsant effects may be related to enhanced glutamate release and, in the case of the limbic and clonic convulsions, activation of AMPA receptors.
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PMID:Induction of seizures by the potent K+ channel-blocking scorpion venom peptide toxins tityustoxin-K(alpha) and pandinustoxin-K(alpha). 1021 33

Five children (3F:2M), in the age group 1 years to 11 years, with Munchausen syndrome by proxy are reported from the Sultanate of Oman. They were seen over a four years period from 1996-1999. In all these children, the mother came up with history of uncontrolled epilepsy. Carbamazepine was the most common antiepileptic drug used. One of these children remained hospitalized elsewhere for nearly 9 months, as a case of uncontrolled status epilepticus. It took 18 months to 6 years (mean 2.8 years) to establish the diagnosis and the mother was the offender in all. The main lead to diagnosis, was the disparity between history and clinical presentation to hospital. The carbamazepine levels were several times above the upper limit of therapeutic range. Munchausen syndrome by proxy very much exists here, but is possibly less recognized and needs immediate attention to formulate policies to identify and manage these children. It is necessary to create awareness even in the medical community, to recognise this problem. There is an urgent need to develop a child protection council at the national or regional level.
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PMID:Munchausen syndrome by proxy. 1150 Jun 87

The causes and mechanisms underlying multidrug resistance (MDR) in epilepsy are still elusive and may depend on inadequate drug concentration in crucial brain areas. We studied whether limbic seizures or anticonvulsant drug treatments in rodents enhance the brain expression of the MDR gene (mdr) encoding a permeability glycoprotein (P-gp) involved in MDR to various cancer chemotherapeutic agents. We also investigated whether changes in P-gp levels affect anticonvulsant drug concentrations in the brain. Mdr mRNA measured by RT-PCR increased by 85% on average in the mouse hippocampus 3-24 hr after kainic acid-induced limbic seizures, returning to control levels by 72 hr. Treatment with therapeutic doses of phenytoin or carbamazepine for 7 d did not change mdr mRNA expression in the mouse hippocampus 1-72 hr after the last drug administration. Six hours after seizures, the brain/plasma ratio of phenytoin was reduced by 30% and its extracellular concentration estimated by microdialysis was increased by twofold compared with control mice. Knock-out mice (mdr1a/b -/-) lacking P-gp protein showed a 46% increase in phenytoin concentrations in the hippocampus 1 and 4 hr after injection compared with wild-type mice. A significant 23% increase was found in the cerebellum at 1 hr and in the cortex at 4 hr. Carbamazepine concentrations were measurable in the hippocampus at 3 hr in mdr1a/b -/- mice, whereas they were undetectable at the same time interval in wild-type mice. In rats having spontaneous seizures 3 months after electrically induced status epilepticus, mdr1 mRNA levels were enhanced by 1.8-fold and fivefold on average in the hippocampus and entorhinal cortex, respectively. Thus, changes in P-gp mRNA levels occur in limbic areas after both acute and chronic epileptic activity. P-gp alterations significantly affect antiepileptic drugs concentrations in the brain, suggesting that seizure-induced mdr mRNA expression contributes to MDR in epilepsy.
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PMID:Limbic seizures induce P-glycoprotein in rodent brain: functional implications for pharmacoresistance. 1212 45

Selecting a specific antiepileptic drug for the treatment of seizures in those with mental retardation requires a balance of the drug's likely efficacy for both seizures and comorbid disorders versus adverse events. Phenobarbital is the most commonly used of the barbiturate drugs. Phenytoin is actually one of the best tolerated AEDs (side effects in most patients are signs of neurotoxicity). Carbamazepine is the drug of choice for many neurologists for the treatment of partial epilepsy, with a relative lack of sedation and low incidence of cosmetic, cognitive, and behavioral side effects. For more than 30 years, valproate has been available for treatment of generalized and partial seizures, convulsive or nonconvulsive. For this reason, it is used in the treatment of epilepsy in the multiply handicapped and mentally retarded. Benzodiazepines are the drug of choice for treatment of status epilepticus; however, good medical control requires early diagnosis and treatment.
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PMID:Treatment considerations: traditional antiepileptic drugs. 1260 8

Nonconvulsive status epilepticus can be confused with psychiatric disorders. Inappropriate drug treatment can represent a precipitating factor. We describe two patients with idiopathic generalized epilepsy in whom nonconvulsive status epilepticus, aggravated by carbamazepine, was misdiagnosed as psychiatric disorder. A 14-year-old girl experienced a tonic-clonic seizure at age 12 years preceded by monthly episodes of confusion with awkward behavior since age 9 years. She was treated with carbamazepine, and the episodes of confusion became more frequent, leading to a diagnosis of dissociative disorder. An electroencephalogram during one of these episodes revealed nonconvulsive status epilepticus. Substitution of carbamazepine with valproic acid controlled the episodes of status epilepticus. A 23-year-old woman presented at age 16 years with a tonic-clonic seizure. Since early adolescence, she had had episodes of depressive mood, worsening of school performances, and facial tics. Carbamazepine treatment caused worsening of the depressive episodes and facial tics. An electroencephalogram during a typical episode revealed nonconvulsive status epilepticus. Carbamazepine substitution with valproate led to seizure freedom and behavioral improvement. Nonconvulsive status epilepticus should be suspected and searched for in patients with epileptic seizures and ictal or fluctuating behavioral disorders.
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PMID:Nonconvulsive status epilepticus precipitated by carbamazepine presenting as dissociative and affective disorders in adolescents. 1622 18

Non-convulsive status epilepticus (NCSE) is relatively rare, but recognized condition observed in non-epileptic comatose patients. In coma state NCSE may be precipitated by stroke, severe electrolyte disturbance, acute intoxication, infection, traumatic brain injury and etc. All these critical disorders can cause coma themselves and without clinical EEG investigation it is impossible to attribute impaired consciousness to NCSE, while the condition can be responsive to anticonvulsant medication. The proper and rapid diagnosis of NCSE is challenging, because it can severely impact the patient and often is a treatable and completely reversible state. Case reports describe the state of three comatose patients affected by severe neurological disorders, who were diagnosed as NCSE after EEG investigation. Nor of these patients were noted to have the epileptic seizures and convulsions. The patients were treated with different anticonvulsive medications (Finlepsin, Levetiracetam, Depakin) and fully recovered from coma state. Frequently, physicians could not suspect presence of NCSE in patients with impaired consciousness because of sufficiently complicated underlying illness. Apparently, clinical EEG investigation is useful to be performed in all comatose patients.
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PMID:Non-convulsive status epilepticus in comatose patients (case reports). 2285 43


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