salicylates and Epilepsy

Topics: Acidosis; Bicarbonates; Biguanides; Diabetes Mellitus; Epilepsy; Ethanol; Fructose; Heart Failure; Humans; Hypoglycemic Agents; Lactates; Leukocytosis; Methanol; Neoplasms; Physical Exertion; Salicylates; Shock

Valproic acid has become a regular component of antiepileptic therapy. Generally it is used against genetically caused, primary generalized epilepsies with bilateral hypersynchronous neuronal discharges in the EEG. An improvement can also be observed by Valproic acid-treatment for secondary generalized and partial epilepsies. Therapeutic results could possibly be improved through a consideration of the serum concentration of valproic acid. Some of the commercial preparations contain the sodium salt of Valproic acid. The free acid which is quickly absorbed, is released in the stomach (tablet) or in the intestine (dragee). The half life is about 15 to 17 hours (one finds a range of 6 to 20 hours in the literature). In view of the half life, it is recommended that the daily dose should be divided into three single doses. About 84 to 95% of the substance is protein bound. Up to now, clinically relevant observations concerning the displacement of valproic acid from its protein binding are unknown. Recently in in vitro studies a decreased protein binding of valproic acid due to phenylbutazone, salicylic acid, and sulfadimethoxine and vice versa, a displacement of phenobarbital and phenytoin caused by valproic acid could be demonstrated. The therapeutic range of the serum level was between 50 and 120 mcg/ml. Individual patients showed that the dispensed dose did not reliably yield the expected serum levels. The necessary daily dose lies for adults between 600 and 2400 mg, in children between 15 and 150 mg/kg. The wide range of allowable dosis is dependent on whether or not valproic acid is to be given in conjunction with other antiepileptic drugs. When phenobarbital and valproic acid are given in conjunction one should be alert for a rise in the phenobarbital serum level. Results of studies in which valproic acid was combined with several other antiepileptic and psychotropic drugs are reported. The majority of the researchers determine a clear parallelism between clinical improvement and a normalization of the EEG in primary generalized epilepsies with bilateral synchronous 3/sec. spikes and waves. The background activity, determined by visual inspection, is not affected. Few workers discuss the correlation of the side effects of valproic acid and its serum level. Tiredness and impaired function of thrombocytes has been observed to be dependent on the valproic acid plasma level.

Topics: Blood Platelets; Drug Interactions; Electroencephalography; Epilepsy; Fatigue; Half-Life; Humans; Phenobarbital; Phenylbutazone; Phenytoin; Protein Binding; Salicylates; Sulfadimethoxine; Valerates; Valproic Acid

Topics: Antihypertensive Agents; Blood Coagulation Disorders; Cardiovascular Diseases; Coumarins; Drug Interactions; Epilepsy; Heparin; Humans; Hypertension; Lidocaine; Mental Disorders; Pharmaceutical Preparations; Phenothiazines; Phenytoin; Procainamide; Salicylates

Topics: Asthma; Epilepsy; Hypoxia; Muscle Relaxants, Central; Myasthenia Gravis; Salicylates; Tetanus; Toxicology; Wounds and Injuries

Hypoxia preconditioning states that a sublethal hypoxia period will afford neuroprotection against a second harmful event. In our experiments, we carried out a procedure for the development of hypoxia preconditioning in adult male Wistar rats using hypoxic exposure (9% O(2); 91% N(2)) for 1 h. The protection against pentylenetetrazol (PTZ)-induced seizures was studied. For this, rats were tested by a single injection of PTZ (55 mg/kg i.p.) on days 1-21 after hypoxia exposure. The hypoxia exposure significantly prevented the development of acute PTZ convulsion at different times after hypoxia. The present study was designed to determine the effect of N-t-butyl-alpha-phenylnitrone (PBN), an electron-trapping agent and free radical scavenger, on hypoxia preconditioning against PTZ seizures 7 days after hypoxia exposure. PBN abolished the protective action of hypoxia exposure. The generation of free hydroxyl radicals in the brains of animals exposed to hypoxia was determined in a second experiment. For this purpose, the rats were i. p. pretreated with 30 mg/kg PBN and NaCl, respectively, 20 min before the start of hypoxia exposure. Forty-five minutes later the rats were i.p. injected with 300 mg/kg sodium salicylate and once again exposed to hypoxia for 15 min. Immediately after that the animals were decapitated and the free hydroxyl radicals and the salicylate content were estimated in the whole brain without cerebellum. Hypoxia preconditioned animals pretreated with NaCl showed a significantly higher extent of free hydroxyl radicals in the brain compared with PBN-injected preconditioned animals and with naive and sham exposed controls. The results pointed out that the generation of free reactive oxygen species under hypoxic conditions in the brain is involved in the development of the hypoxic preconditioning phenomenon.

Topics: Animals; Brain; Convulsants; Epilepsy; Hydroxyl Radical; Hypoxia, Brain; Ischemic Preconditioning; Male; Pentylenetetrazole; Rats; Rats, Wistar; Salicylates

In five of six epileptic children who were taking 18 to 49 mg/kg/day valproic acid (VPA), the steady-state serum free fractions of VPA rose from 12% to 43% when antipyretic doses of aspirin were also taken. Mean total VPA half-life (t1/2) rose from 10.4 +/- 2.7 to 12.9 +/- 1.8 hr and mean free VPA t1/2 rose from 6.7 +/- to 2.1 to 8.9 +2- 3.0 hr when salicylate was present in the serum. The in vitro albumin binding association constant (ka) for VPA was decreased by salicylate, but the in vivo ka value was not affected. The 12-hr (trough) concentrations of both free and total VPA were higher in the presence of serum salicylate in five of six patients. Renal excretion of unchanged VPA decreased in five of six patients, but the VPA carboxyl conjugate metabolite-excretion patterns were not consistently affected. Salicylate appeared to displace VPA from serum albumin in vivo, but the increased VPA t1/2 and changes in VPA elimination patterns suggest that serum salicylate also altered VPA metabolism.

Topics: Aspirin; Blood Proteins; Child; Child, Preschool; Drug Interactions; Epilepsy; Female; Humans; Kinetics; Male; Protein Binding; Salicylates; Valproic Acid

The effects of a dietary manipulation on seizure frequency and activity level of a 3 1/2-year-old male with tuberous sclerosis, mental retardation, and uncontrolled seizures were assessed. Using a reversal design, the Feingold (K-P) diet was presented and withdrawn three times, while the medication regimen remained unaltered. Every application of the K-P diet resulted in substantial reductions in seizure frequency. During a 21-week follow-up, seizure frequency remained low despite the phasing out of one drug, and seizures were reportedly eliminated 1 year later. Brief objective measures of hyperactivity failed to show any effect due to the diet changes.

Topics: Child, Preschool; Diet; Epilepsy; Food Additives; Humans; Hyperkinesis; Male; Salicylates

The interactions of antiepileptic drugs in multiple drug treatment have been discussed. Although some combinations may lead to predictable increase or decrease of clearance of the respective drugs, most combinations will individually lead to a reduced predictability. Monitoring plasma concentrations may lead to adaptations of the choice of the drug and of the dosage regimen. Also physiological conditions control the individual clearance of antiepileptic drugs.

Topics: Animals; Anticonvulsants; Carbamazepine; Drug Interactions; Epilepsy; Ethanol; Female; Humans; Kinetics; Male; Phenobarbital; Phenytoin; Pregnancy; Primidone; Salicylates

Topics: Child; Child Behavior Disorders; Child, Preschool; Epilepsy; Food Additives; Humans; Hyperkinesis; Salicylates

A study of 170 patients with juvenile rheumatoid arthritis and a review of the literature indicate that this disease can significantly affect the central nervous system. Signs of CNS dysfunction were observed in 13 children. During the acute toxic stages the EEG is abnormal in many cases. Other manifestations of toxic encephalopathy such as irritability, drowsiness, stupor, convulsions and marked meningismus may be evident in severe cases. Meningitis is often suspected but ruled out by the finding of normal CSF. Steroids can rapidly improve the condition of these children. If ;unexplained' seizures occur during the chronic stage, the diagnosis of cerebral vasculitis should be entertained.

Topics: Arthritis, Juvenile; Central Nervous System Diseases; Child; Child, Preschool; Electroencephalography; Epilepsy; Humans; Infant; Male; Meningism; Prednisone; Salicylates; Seizures; Spinal Puncture

Topics: Blood; Blood Proteins; Epilepsy; Epilepsy, Tonic-Clonic; Female; Humans; Hyperbilirubinemia; In Vitro Techniques; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Phenytoin; Protein Binding; Salicylates; Serum Albumin; Umbilical Cord; Uremia

Topics: Adolescent; Anticonvulsants; Cerebral Angiography; Child; Epilepsies, Partial; Epilepsy; Epilepsy, Absence; Epilepsy, Temporal Lobe; Epilepsy, Tonic-Clonic; Female; Humans; Male; Penicillins; Pneumoencephalography; Rheumatic Fever; Salicylates

The plasma levels of the urate-binding alpha(1)-alpha(2)-globulin, as determined by its urate-binding capacity, have been recorded in 19 individuals from two gouty kindreds. A significantly reduced binding capacity, accounting for 13-30% of the mean value obtained in healthy, unrelated control subjects, was found in all cases of gout and in the single case of essential hyperuricemia included in the present study. In addition, six apparently healthy members of one of these kindreds also exhibited this characteristic. The distribution of the characteristic in three subsequent generations from this kindred further supported the hypothesis that the reduced binding capacity was inherited as an autosomal trait for which affected subjects were heterozygous. Based on the present observation, the mechanisms of inheritance in primary gout are discussed with special emphasis on the possible cooperation of genetic and environmental factors.

Topics: Adult; Alpha-Globulins; Arthritis; Autoradiography; Chromatography, Gel; Epilepsy; Female; Gout; Heterozygote; Humans; Immunoelectrophoresis; Kidney; Male; Middle Aged; Migraine Disorders; Narcolepsy; Pedigree; Protein Binding; Puberty; Salicylates; Spectrophotometry; Uric Acid

Topics: Anticonvulsants; Caffeine; Diuretics; Epilepsy; Salicylates