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

This double-blind study sought to discover if cranial electrotherapy stimulation (CES), which is a known treatment of depression, anxiety and insomnia in non-head-injured patients, could be an effective, drug-free treatment of stress-related symptoms in the closed-head-injured (CHI) patient. In this study 10 CHI patients treated for 45 min daily, 4 days a week for 3 weeks, responded significantly on all negative mood factors of the Profile Of Mood States, while five sham-treated and six placebo controls did not. While the majority of the patients were known seizure cases, no patient suffered a seizure during CES therapy. No placebo effects were found, nor were any negative effects from CES treatment seen.
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PMID:The use of cranial electrotherapy stimulation in the treatment of closed-head-injured patients. 808 50

Among some 14 new antiepileptic drugs (AEDs), those most extensively tested in humans include felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OCBZ), vigabatrin (VGB), and zonisamide (ZNS). All are currently marketed in some but not all countries. Although no large, comparative studies on efficacy have been conducted, all of these new AEDs are effective in adult localization-related epilepsies, and some have activity in specific syndromes. Although these drugs all have some CNS side effects, especially when administered in combination with other AEDs, they also all have low toxicity profiles. The availability of AEDs with different mechanisms of action may facilitate rational polytherapy. FBM is not teratogenic in animals. Half-life of FBM in humans is 11-28 h. Daily FBM dosages are 15-45 mg/kg in children and 2,400-4,800 mg in adults. Side effects include insomnia and anorexia, with weight loss. FBM increases phenytoin (PHT) and valproate (VPA) concentrations, and FBM concentration may be affected by other drugs. It is available in the United States for treatment of Lennox-Gastaut syndrome and partial seizures in adults. GBP is very water soluble. Half-life of GBP in humans is 5-7 h and daily dosages range from 900 to 2,400 mg in adults. Few side effects have been observed. GBP is not metabolized by the liver and has no drug interactions. It is available in the United Kingdom and the United States. LTG has no teratogenicity in animal models. Half-life of LTG in humans depends on co-medication: with enzyme inducers it is 15-24 h, and with VPA it is approximately 60 h. LTG dosages are 100-600 mg/day in adults. LTG is available in Europe. OCBZ is rapidly metabolized to 10,11-dihydro-10-hydroxy-carbazepine (MHD), the active compound. Animal studies have shown similar efficacy but superior toxicity to carbamazepine (CBZ) in animal models. For MHD, half-life ranges from 10 to 15 h in patients. OCBZ dosages range from 300 to 1,800 mg/day. VGB is a potent, irreversible inhibitor of GABA transaminase which elevates GABA levels in the CNS. Daily dosages of 2,000-4,000 mg of VGB are needed in adults. Although intramyelinic edema has developed in rats and dogs, it has not yet presented in other mammals or humans. ZNS is a sulfonamide effective in animal models of epilepsy. Half-life of ZNS is 27-36 h. ZNS daily dosage is 400-600 mg. ZNS has been effective in some cases of Baltic myoclonic epilepsy.
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PMID:Antiepileptic drugs in development: prospects for the near future. 817 17

Felbamate (FBM) is an effective and safe novel antiepileptic drug (AED) for add-on treatment in adults with refractory partial seizures as shown in three pivotal controlled trials. In addition, FBM is effective and safe in monotherapy in adults with refractory partial seizures. FBM is also effective and safe as add-on therapy for children and adults with refractory Lennox-Gastaut syndrome. The effective daily dosage is approximately 30-45 mg/kg divided into three or four doses with resulting plasma concentrations of 50-80 mg/L. The safety profile of FBM is limited to mild gastrointestinal complaints, insomnia, and nonspecific CNS symptoms. Six pivotal controlled trials, with both classic and innovative design, showed that FBM is a useful AED.
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PMID:Felbamate: successful development of a new compound for the treatment of epilepsy. 824 76

Sleep-related disorders are revisited in the light of the physiological modality of NREM sleep expressed by the cyclic alternating pattern (CAP). Owing to its fluctuating properties on vigilance, muscle tone, and vegetative activities, CAP represents a highly favorable condition for the occurrence of interictal generalized and focal lesional EEG discharges, for motor seizures, and for periodic jerks in nocturnal myoclonus. All these manifestations are significantly associated with the components of activation during CAP, i.e., the A phases. On the contrary, the B phases of CAP appear chronologically linked to inhibitory phenomena in epileptic patients and in nocturnal myoclonus. The two phases of CAP seem especially involved in sleep apnea syndrome, where respiration is interrupted during a phase B and restored during a phase A. CAP rate, that measures the effort of the brain to maintain sleep, is increased by all conditions that induce vigilance instability such as noise, clinical insomnia, interictal EEG paroxysms, nocturnal seizures, periodic leg movements, and in certain extreme pathologic conditions such as Creutzfeldt-Jakob disease and stage 2 coma.
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PMID:Clinical applications of cyclic alternating pattern. 824 61

The central autonomic network (CAN) is an integral component of an internal regulation system through which the brain controls visceromotor, neuroendocrine, pain, and behavioral responses essential for survival. It includes the insular cortex, amygdala, hypothalamus, periaqueductal gray matter, parabrachial complex, nucleus of the tractus solitarius, and ventrolateral medulla. Inputs to the CAN are multiple, including viscerosensory inputs relayed on the nucleus of the tractus solitarius and humoral inputs relayed through the circumventricular organs. The CAN controls preganglionic sympathetic and parasympathetic, neuroendocrine, respiratory, and sphincter motoneurons. The CAN is characterized by reciprocal interconnections, parallel organization, state-dependent activity, and neurochemical complexity. The insular cortex and amygdala mediate high-order autonomic control, and their involvement in seizures or stroke may produce severe cardiac arrhythmias and other autonomic manifestations. The paraventricular and other hypothalamic nuclei contain mixed neuronal populations that control specific subsets of preganglionic sympathetic and parasympathetic neurons. Hypothalamic autonomic disorders commonly produce hypothermia or hyperthermia. Hyperthermia and autonomic hyperactivity occur in patients with head trauma, hydrocephalus, neuroleptic malignant syndrome, and fatal familial insomnia. In the medulla, the nucleus of the tractus solitarius and ventrolateral medulla contain a network of respiratory, cardiovagal, and vasomotor neurons. Medullary autonomic disorders may cause orthostatic hypotension, paroxysmal hypertension, and sleep apnea. Neurologic catastrophes, such as subarachnoid hemorrhage, may produce cardiac arrhythmias, myocardial injury, hypertension, and pulmonary edema. Multiple system atrophy affects preganglionic autonomic, respiratory, and neuroendocrine outputs. The CAN may be critically involved in panic disorders, essential hypertension, obesity, and other medical conditions.
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PMID:The central autonomic network: functional organization, dysfunction, and perspective. 841 66

This study enrolled patients with complicated urinary tract infections (UTIs) in a trial to determine the efficacy and safety of sequential therapy with intravenous fleroxacin (first 3 days) followed by oral fleroxacin, for a total course of 7-14 days, both administered at a dosage of 400 mg once a day. We enrolled 68 patients with complicated UTIs or acute pyelonephritis, 32 of whom were evaluable for bacteriologic and clinical efficacy. The pathogens isolated included Escherichia coli, 15; enterococci, 9; miscellaneous, 15. Intravenous fleroxacin was given for a mean of 3.2 days, followed by oral fleroxacin for a mean of 5.3 days. A total of 27 patients were clinically cured (84%), two improved, and three failed. A total of 26 patients were bacteriologically cured (81%), and six failed (19%). The bacteria that were not eradicated included enterococci, 4; Staphylococcus epidermidis, 1; and Pseudomonas species, 1. One enterococcal isolate became resistant to fleroxacin. Four patients were bacteremic (E. coli, 3; Proteus mirabilis, 1); the pathogen was eradicated in all cases. Two patients developed urinary enterococcal superinfections. A total of 12 patients experienced 16 adverse reactions remotely, possibly, or probably related to fleroxacin (insomnia, 3; dizziness, 2; miscellaneous, 11). One patient had a grand mal seizure after aspirating gastric contents; the seizure was thought to be only remotely related to the study drug. Fleroxacin was discontinued in two patients because of adverse effects (phlebitis at intravenous access site, 1; anxiety and insomnia, 1). Only minor and asymptomatic laboratory abnormalities were observed. All clinical and laboratory abnormalities resolved with discontinuation of the study drug. Fleroxacin is a safe and effective antibiotic for sequential intravenous and oral treatment of acute pyelonephritis and complicated UTIs. Enterococci may be problematic pathogens, as reported with other fluoroquinolones.
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PMID:A sequential study of intravenous and oral fleroxacin in the treatment of complicated urinary tract infection. 845 68

Benzodiazepines have a wide variety of indications. However, CNS and psychiatric adverse reactions, tolerance, and withdrawal effects of benzodiazepines are becoming increasingly recognized and must be better understood for proper drug use. Certain benzodiazepines are associated with memory impairment and other cognitive defects and hyperexcitability phenomena during treatment (early-morning insomnia, daytime anxiety) and following withdrawal (rebound insomnia and anxiety, seizures). Elimination half-life, receptor-binding affinity, effects on the locus coeruleus-norepinephrine (LC-NE) and hypothalamic-pituitary-adrenal (HPA) axes, and the interaction of these factors appear to be major determinants of frequency and severity of these untoward effects. Rapid drug elimination and high receptor-binding affinity were initially suggested as primary underlying factors which determine frequency, severity, and type of the side effects of benzodiazepines during administration and withdrawal. Newer data and information on triazolobenzodiazepines indicate that these psychiatric adverse reactions also relate to whether the benzodiazepine has strong direct effects on the LC-NE and HPA systems. Initial suppression of the LC-NE and HPA systems is followed, on an interdose basis, by a significant rebound and activation. This repetitive pattern of suppression followed by rebound results in a neurophysiologic and behavioral sensitization (kindling) of the limbic system and consequently contributes to central nervous system and psychiatric adverse reactions. The tendency of certain of these side effects to worsen over time supports empirically this neurophysiologic and biochemical model.
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PMID:Benzodiazepine side effects: role of pharmacokinetics and pharmacodynamics. 857 15

During December 1993-September 1995, the Bureau of Food and Drug Safety, Texas Department of Health (TDH), received approximately 500 reports of adverse events in persons who consumed dietary supplement products containing ephedrine and associated alkaloids (pseudoephedrine, norephedrine, and N-methyl ephedrine). This total included reports by individuals and reports identified by the Bureau of Epidemiology, TDH, in a review of records from the six centers of the Texas Poison Center Network. Reported adverse events ranged in severity from tremor and headache to death in eight ephedrine users and included reports of stroke, myocardial infarction, chest pain, seizures, insomnia, nausea and vomiting, fatigue, and dizziness. Seven of the eight reported fatalities were attributed to myocardial infarction or cerebrovascular accident. This report describes three patients in which the recommended dosage for the dietary supplements reportedly was not exceeded, summarizes results from ongoing investigations, and underscores the potential health risks associated with the use of products containing ephedrine.
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PMID:Adverse events associated with ephedrine-containing products--Texas, December 1993-September 1995. 877 3

Benzodiazepine drugs (BZ) are used for anxiety, insomnia, and seizures. They worsen memory, especially in large doses, but the mechanism of this action is uncertain. In micromolar concentrations, benzodiazepines have been shown to reduce long-term potentiation (LTP), which could be a cellular basis for their amnesic action. We have found that the LTP-inhibiting effects of BZ occur in the nanomolar concentrations attained in humans, and that this effect occurs through modulation of GABAA receptor function. We recorded extracellular synaptic input/output (I/O) curves for population spikes (PS) and EPSPs in rat hippocampal slices before and after induction of LTP. LTP increased maximal PS and EPSPs and shifted I/O curves for PS and EPSPs to the left, reflecting increased synaptic responsiveness after LTP. Curves relating EPSPs to PS were also shifted, so that after LTP larger PS were elicited for the same size EPSP (E-S potentiation). Midazolam (0.5 microM) markedly inhibited the left-shift in PS I/O curves due to E-S potentiation but did not significantly affect other parameters. 8-Phenyltheophylline (10 microM), an adenosine receptor antagonist, did not prevent midazolam inhibition of LTP. Bicuculline, a GABAA receptor antagonist, caused a dose-dependent antagonism of midazolam's LTP inhibition. Our results suggest that benzodiazepines reduce LTP primarily through reduction of E-S potentiation, and that this effect occurs through modulation of GABAA receptor function. This could in part account for the ability of benzodiazepines to disturb new memory formation.
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PMID:Midazolam inhibits long-term potentiation through modulation of GABAA receptors. 878 10

Triazolam (TZ) is a triazolobenzodiazepine used in the treatment of insomnia that possesses significant anticonvulsant properties. Despite the widespread use of this drug, detailed pharmacokinetic-pharmacodynamic information is lacking, especially with respect to inhibition of seizure activity. TZ disposition has been described previously by methods with limited specificity, and the concentration-anticonvulsant effect relationship has not been characterized. The current studies were undertaken to examine TZ disposition with a specific HPLC method, and to evaluate the relationship between anticonvulsant effect and concentration in Sprague-Dawley rats. TZ pharmacokinetics were characterized after bolus or infusion administration; in a separate experiment, TZ pharmacodynamics were assessed with pentylenetetrazol-induced seizures. The systemic disposition of TZ could be described with a two-compartment model; systemic clearance ranged from 2.45 to 5.30 L/h/ kg, steady-state volume of distribution ranged from 2.10 to 4.02 L/kg, and mean residence time ranged from 47 to 65 min. The concentration-effect relationship was well described by a simple Emax model: Emax, expressed as the ratio of post-TZ to pre-TZ threshold convulsant doses of pentylenetetrazol, was 9.9 +/- 0.7, and the EC50 values were 10.0 +/- 4.6 ng/mL and 34.8 +/- 9.0 ng/g in serum and whole brain tissue, respectively. Under single-dose conditions, TZ is a very potent anticonvulsant in the rat pentylenetetrazol seizure model.
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PMID:Anticonvulsant pharmacodynamics and disposition of triazolam in rats. 887 93


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