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)

Gamma-aminobutyric acid (GABA), one of the main inhibitory neurotransmitters in the brain, interacts with three types of receptors for GABA--GABA(A), GABA(B) and GABA(C). GABA(A) receptors, associated with binding sites for benzodiazepines and barbiturates in the form of a receptor complex, control opening of the chloride channel. When GABA binds to the receptor complex, the channel is opened and chloride anions enter the neuron, which is finally hyperpolarized. GABA(B) receptors are metabotropic, linked to a cascade of second messengers whilst the physiological meaning of ionotropic GABA(C) receptors, mainly located in the retina, is generally unknown. Novel antiepileptic drugs acting selectively through the GABA-ergic system are tiagabine and vigabatrin. The former inhibits neuronal and glial uptake of GABA whilst the latter increases the synaptic concentration of GABA by inhibition of GABA-aminotransferase. Gabapentin, designed as a precursor of GABA easily entering the brain, was shown to increase brain synaptic GABA. This antiepileptic drug also decreases influx of calcium ions into neurons via a specific subunit of voltage-dependent calcium channels. Conventional antiepileptics generally inhibit sodium currents (carbamazepine, phenobarbital, phenytoin, valproate) or enhance GABA-ergic inhibition (benzodiazepines, phenobarbital, valproate). Ethosuximide, mainly controlling absences, reduces calcium currents via T-type calcium channels. Novel antiepileptic drugs, mainly associated with an inhibition of voltage-dependent sodium channels are lamotrigine and oxcarbazepine. Since glutamate-mediated excitation is involved in the generation of seizure activity, some antiepileptics are targeting glutamatergic receptors--for instance, felbamate, phenobarbital, and topiramate. Besides, they also inhibit sodium currents. Zonisamide, apparently sharing this common mechanism, also reduces the concentration of free radicals. Novel antiepileptic drugs are better tolerated by epileptic patients and practically are devoid of important pharmacokinetic drug interactions.
 ...
PMID:Mechanisms of action of antiepileptic drugs. 1563 74

Bupropion, a unique, non-nicotine smoking cessation aid and an effective antidepressant, is well known to produce seizures following overdosing in humans. However, the experimental background for the usefulness of antiepileptic drugs in the protection against bupropion-induced convulsions has not been established yet. Therefore, we tested if the antiepileptic drugs were able to protect mice against clonic convulsions induced by intraperitoneally (i.p.) administered bupropion in the CD97 dose (139.5 mg/kg). Among 13 tested drugs, clonazepam showed the greatest potency (dose-dependent full protection; ED50 = 0.06 mg/kg, i.p.). No signs of locomotor impairment were observed in the rotarod test after anticonvulsive doses of clonazepam, resulting in a broad therapeutic window and favorable protective index (PI) (33.3). Gabapentin produced dose-dependent protection against convulsions at nontoxic doses (up to 1000 mg/kg), having PI>29. Diazepam in a very high dose showed full protection but its PI (1.7) was much less favorable than that of clonazepam. The PI values for ethosuximide, phenobarbital and valproate were slightly higher than unity and lower than 2, and for topiramate and felbamate were lower than unity. Phenytoin, carbamazepine, and lamotrigine as well as tiagabine failed to block the convulsant effects of bupropion even at doses that caused severe motor impairment. Our results encourage clinical testing of clonazepam against seizures developing after bupropion overdose.
 ...
PMID:Bupropion-induced convulsions: preclinical evaluation of antiepileptic drugs. 1586 10

Gabapentin is an antiepileptic drug approved for the treatment of postherpetic neuralgia and as adjunctive therapy for partial seizures. The drug has been shown to be safe and nontoxic. The current literature has limited reports of neurologic toxicity associated with gabapentin therapy in patients with or without renal dysfunction. We describe the case of a 75-year-old man with renal dysfunction who developed neurologic toxicity due to gabapentin accumulation. Future studies are warranted to confirm the neurologic adverse effects of gabapentin, including any additional risks in patients with renal dysfunction.
 ...
PMID:Gabapentin-induced neurologic toxicities. 1630 1

Summary Gabapentin is an antiepileptic drug indicated for the treatment of partial seizures in children. Many studies have proved its analgesic action in the treatment of neuropathic pain in adults and we have noticed an analgesic action of gabapentin in neuropathic pain in children. Five patients treated in the Children's Hospital Pain Control Service for intractable neuropathic pain were included in gabapentin treatment. Four were cancer patients and one suffered from neuropathic pain in the neck (C3). The visual analog scale (VAS) scores of pain were compared before and during treatment with gabapentin. We noticed a rapid improvement, in 1 week, of our patients' VAS scores (from 9 or 10 to 4 or 3) with minimal adverse effects. In the follow-up period of 6 months we gradually reduced the dose of gabapentin. Our findings are that gabapentin should be included earlier in the treatment of neuropathic pain in adolescents, because it rapidly improves analgesia and has minimal side effects.
 ...
PMID:Experience with gabapentin for neuropathic pain in adolescents: report of five cases. 1649 Jan

We posted a questionnaire on epilepsy to all 375 GPs in Cork and Kerry (population 500,000) The questionnaire consisted of 10 sections, covering areas like GP demographics, initial referral practice following a first seizure, advice given to patients and GP's attitudes towards patients with epilepsy. The main focus of the study was GP awareness of 7 of the newer anti-epileptics and their side effects. There was a response rate of 46.7% (175) and revealed that the majority (87%) initially refer patients to a neurologist for further assessment. The majority of GPs gave patients advice about driving, AED side effects, interaction with the OCP and pregnancy counselling. GP awareness of the newer anti-epileptics is very variable with Gabapentin and Lamotrigine having the highest GP awareness rates. Almost 25% of GPs would initiate treatment following a first time seizure although only 30% would change therapy initiated by a consultant neurologist. Finally the majority of GPs were unhappy with the level of access to neurologists and 95% of GPs felt that the provision of an Epilepsy Clinical Nurse Specialist would help alleviate the problem.
 ...
PMID:Management of epilepsy in the community. 1654 22

Using a large US health insurance claims database, we identified all persons aged > or =18 years with > or =2 medical encounters with diagnoses of cancer and > or =2 medical encounters with diagnoses of painful neuropathies in calendar year (CY) 2000; persons with seizure disorders or depression were excluded. We then examined the use of antiepileptics (AEDs), tricyclic antidepressants (TCAs) and other pain-related pharmacotherapy among these selected persons, as proxied by pharmacy dispenses. A total of 956 persons were identified who met all entry criteria; 17% received AEDs in CY2000 and 14% received TCAs. Gabapentin was the most widely used AED (92% of all AED patients); amitriptyline was the most widely used TCA (79% of all TCA patients). Patients who received AEDs and/or TCAs were similar in age, gender and the presence of metastases to those who had not received these medications; they were more likely to have received other pain-related therapies, however, including short-acting opioids (73% vs. 53%; P < 0.01) and long-acting opioids (23% vs. 8%; P < 0.01). Use of AEDs and TCAs appears to be relatively low among cancer patients with painful neuropathies. Further research is needed to better understand reasons for this finding, as well as its potential implications for pain management in this patient population.
 ...
PMID:Use of antiepileptics and tricyclic antidepressants in cancer patients with neuropathic pain. 1664 61

This double-blind study was conducted to evaluate the efficacy and safety of gabapentin 1200 mg/day and 1800 mg/day (t.i.d.) compared to placebo as an adjunctive therapy in patients with refractory epilepsy. Patients were included when they had partial seizures at least eight times during a 12-week baseline period despite treatment with one to two antiepileptic drugs. After baseline, eligible patients were randomized to gabapentin 1200 mg/day, 1800 mg/day, or placebo for 12-week treatment. The primary end-point, response ratio, was derived from seizure frequencies during treatment and baseline period based upon the seizure daily record by a patient. Of the 209 randomized patients, 86 received gabapentin 1200 mg/day, 41 received gabapentin 1800 mg/day, and 82 received placebo. A statistically significant difference was found between each of the two gabapentin groups and placebo for the primary efficacy end-point, response ratio (P < 0.005) with definite dose-response (P < 0.001). More gabapentin patients reported moderate to marked improvement in seizure frequency and intensity/duration of each seizure than placebo patients. Treatment-related adverse events were reported by approximately 65% of patients receiving gabapentin compared to approximately 46% of patients receiving placebo; somnolence and dizziness were the most common events. Gabapentin 1200 mg/day and 1800 mg/day significantly reduced the frequency of refractory seizures compared to placebo. Favorable tolerability of gabapentin was confirmed also in a Japanese population, consistent with previous global studies.
 ...
PMID:Treatment of partial seizures with gabapentin: double-blind, placebo-controlled, parallel-group study. 1688 55

This work was designed to study the influence of drugs during seizures and status epilepticus (SE) induced by pilocarpine and mortality in adult rats. Fluoxetine (10 and 20 mg/kg), NMDA (N-methyl-D-aspartate, 10 and 20 mg/kg), amitriptyline (25 and 50 mg/kg), ketamine (0.5 and 1.0 mg/kg), gabapentin (100 and 150 mg/kg) and pimozide (10 and 20 mg/kg) were administered intraperitoneally, 30 min prior to pilocarpine (400mg/kg, s.c.). The animals were observed (24h) to determine: number of peripheral cholinergic signs, tremors, stereotyped movements, seizures, SE, latency to first seizure and number of deaths after pilocarpine treatment. Fluoxetine, amitriptyline, NMDA, and pimozide had proconvulsant effects in both doses tested. Smaller and higher doses of these drugs no protected and increased pilocarpine-induced seizures and/or mortality. Gabapentin and ketamine protected against seizures and reduced the latency to first seizure. Thus, these results suggest that caution should be taken in the selection of pharmacotherapy and dosages for patients with epilepsy because of the possibility of potentiating convulsive process toxicity.
 ...
PMID:Effect of gabaergic, glutamatergic, antipsychotic and antidepressant drugs on pilocarpine-induced seizures and status epilepticus. 1701 Nov 25

New generation antiepileptic drugs, including gabapentin and tiagabine, are used in monotherapy or in combination with other drugs for specific seizure types. The multidirectional mechanism of activity and varied pharmacological properties of these drugs suggest that they could also be used in the therapy of other diseases. A possible limitation of new generation antiepileptic drugs is the incidence of CNS-related adverse effects. Few studies have assessed the effect of new antiepileptic drugs on electroencephalogram (EEG) recordings in subjects using these drugs for diseases other than epilepsy. The aim of this study was to determine the effects of tiagabine and gabapentin on EEG recordings from the midbrain reticular formation, dorsal hippocampus and frontal cortex in rabbits. Tiagabine was administered orally at a single dose of 5 and 20 mg kg(-1), or repeatedly at a dose of 5 mg kg(-1) (twice a day) for 14 days. Gabapentin was administered orally at a single dose of 25 and 100 mg kg(-1), or repeatedly at a dose of 25 mg kg(-1) (twice a day) for 14 days. Both tiagabine and gabapentin caused changes indicative of CNS inhibitory properties, which may be associated with the adverse effects of the drugs. After repeated doses of the drugs, the changes in EEG recordings were less pronounced than after single doses, which may indicate adaptive changes. The hippocampus was found to be the least sensitive to the effect of gabapentin.
 ...
PMID:Effect of the administration of tiagabine and gabapentin on rabbit electroencephalogram activity. 1703 60

Patients with epilepsy may suffer from renal or hepatic diseases that interfere with their antiepileptic drug (AED) treatment. Furthermore, such diseases may themselves cause seizures. Reduced renal function and hypoalbuminemia lead to accumulation of renally excreted AEDs, such as gabapentin, vigabatrin, topiramate, levetiracetam, and phenytoin. Valproate, lamotrigine, and benzodiazepines are less affected. Low protein-bound AEDs are extensively removed by hemodialysis and supplemental doses are required for dialysis patients. Uremia and related conditions, including intracranial hemorrhage, glucose and electrolyte imbalances, and concomitant drug use, can cause seizures, as can dialysis encephalopathy, primary cerebral lymphoma, fungal infections, and immunosuppressant toxicity in renal transplant recipients. Hepatic dysfunction reduces enzymatic metabolism of AEDs and causes hypoalbuminemia. Gabapentin, topiramate, and levetiracetam are preferred in these conditions, whereas conversely valproate and felbamate are potentially hepatotoxic and should be avoided. Seizures related to hepatic encephalopathy are controlled by oral lactulose or neomycin. Porphyria sufferers may benefit from gabapentin, oxcarbazepine, or levetiracetam. Seizures in Wilson's disease may derive from d-penicillamine-induced pyridoxine deficiency. Effective treatment of seizures in renal and hepatic diseases requires attention to changes in AED pharmacokinetics and adequate care of the underlying illnesses. Monitoring of free drug concentrations is a valuable aid to therapy.
 ...
PMID:Optimizing therapy of seizures in patients with renal or hepatic dysfunction. 1719 Sep 18


<< Previous 1 2 3 4 5 6 7 8 9 10