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)

A patient with Stevens-Johnson syndrome is described, and the literature concerning the etiology, pathophysiology, clinical manifestations, and management of Stevens-Johnson syndrome is reviewed. A 2 1/2-year-old girl was treated with phenobarbital and i.v. ampicillin, followed by oral amoxicillin, for an upper-airway infection, otitis media, and febrile seizures. The fever returned, and she was treated unsuccessfully with penicillin and cefaclor. She was admitted to the hospital and treated with i.v. ampicillin. Within 24 hours an erythematous maculopapular rash developed. Phenobarbital was discontinued and phenytoin was begun. Four days later bullous lesions developed; ampicillin and phenytoin were discontinued, and cefazolin and phenobarbital were given. By the eighth day severe sloughing of the skin occurred over 75% of her body, and mucosal sloughing was apparent. The patient's condition was diagnosed as Stevens-Johnson syndrome. Porcine xenografts were immediately grafted to 75% of her total body surface. Severe lesions of the mouth and pharynx made parenteral nutrient therapy necessary, and ocular complications required the care of an ophthalmologist. Although the skin had healed by 14 days after grafting, another 14 days of treatment for respiratory complications was required. Stevens-Johnson syndrome is a severe exfoliative dermatitis accompanied by fever, inflammation of the gastrointestinal mucosa, and severe purulent conjunctivitis. It is associated with high morbidity and mortality. The etiologic factors may be iatrogenic (e.g., various antibiotics and anticonvulsants), infectious, or idiopathic. Respiratory complications, leukopenia, infections, erosion of the gastrointestinal mucosa, fluid and electrolyte disturbances, and chronic ocular complications may occur.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Management of Stevens-Johnson syndrome. 374 53

Ten cats were stimulated twice a day in the lateral amygdala with low-frequency stimulation of about 3 Hz until generalized convulsion occurred. After the completion of kindling, the longest interpulse interval required for provocation of generalized convulsion (pulse-interval threshold) was determined in each subject. The pulse-interval threshold was 1300 ms in five cats, and 900 ms in five other cats. Then the stability of pulse-interval threshold and of the number of stimulating pulses required for provocation of afterdischarge when the stimulation was delivered with the pulse-interval threshold (pulse-number threshold) was tested. The pulse-interval threshold, pulse-number threshold, and duration of afterdischarge in each stimulation did not change statistically at the interstimulation interval from 24 h to 7 days. Phenobarbital and diphenylhydantoin elevated the pulse-number threshold significantly. We propose that low-frequency kindling is a valuable experimental model of epilepsy in assessing simply and precisely the susceptibility of the epileptic focus itself and the severity of epileptic seizures.
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PMID:Low-frequency kindling as a new experimental model of epilepsy. 377 Jan 22

Baclofen and phenobarbital were tested for anticonvulsant efficacy against limbic seizures produced by i.c.v. infusion of kainic acid (KA) in unanesthetized rats. All rats treated with KA alone developed a prolonged status epilepticus associated with extensive neuronal degeneration. When administered immediately after the KA infusion, baclofen (5 mg/kg i.p.) protected five of six animals against the development of status epilepticus and did not alter the behavioral expression of the residual discrete electrographic seizures. Phenobarbital (40 mg/kg i.p.) given 15 min before KA also prevented the development of status epilepticus in five of six rats, but blocked the behavioral expression of the residual electrographic seizures. In two of five additional rats, baclofen prevented or reversed status epilepticus when administered 50 to 60 min after the end of the KA infusion. The ability of these drugs to prevent KA-induced neuronal degeneration correlated with their anticonvulsant action.
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PMID:Efficacy of baclofen and phenobarbital against the kainic acid limbic seizure-brain damage syndrome. 377 12

Phenobarbital appears to produce similar behavioral effects on mice and humans with excitation at low and sedation or depression at higher doses. If plasma concentrations of phenobarbital reflect levels in other tissue, then brain concentrations producing excitation (near 10 micrograms/g) and depression (near 20 micrograms/g) are not substantially different for the two species. The doses needed to produce these levels are much higher in mice than man. Plasma concentrations of phenobarbital decline during pregnancy in humans. Whether this decline is accompanied by increased seizure frequency has not been confirmed empirically and whether pregnancy influences the frequency of seizures at all is controversial. The reduction in phenobarbital levels in plasma or serum during pregnancy has been confirmed in rodents. Two of these studies however reported no difference brain concentrations of the drug during pregnancy. One study indicated increased potency of the drug, however this was not confirmed by the other two reports. The effects of phenobarbital on the progression of pregnancy and on offspring is not well defined in humans partly because the disease and the treatment effects are confounded. There are a few studies however which suggest that the effects might be drug specific. Animal studies in this area differ substantially from humans in design making any comparison tentative. The effects of the drug on pregnancy and neonates in rodents depends on the method of administering the drug and dose. Drug administration via the diet can provide high blood levels in the dams and causes lowered birthweight as well as several anatomical and hormonal abnormalities in offspring. This procedure, however, also severely reduced food intake and weight gains during pregnancy which might confound drug effects with nutritional deficiency. The drug can be injected in doses which produce plasma levels well within the therapeutic range for humans. Under these conditions the drug is less detrimental to the progression of pregnancy, however, the higher doses can increase neonatal mortality and reduce body weight of surviving offspring. Although mortality and body weight are not adversely effected by lower doses, changes are still apparent in the behavior as well as several biochemical parameters. Fostering studies on animals suggest that the effects of maternal injections of phenobarbital on offspring are due to the IN UTERO exposure rather than postnatal maternal factors and that effects produced by fostering itself may be confounded with the drug effects.
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PMID:Phenobarbital during pregnancy in mouse and man. 378 54

The pharmacokinetics of antiepileptic drugs used for the treatment of human epilepsies is reviewed for dogs and cats. In dogs, especially phenobarbital and primidone must be regarded as useful drugs for chronic treatment on account of their elimination rate and bioavailability. Phenytoin, carbamazepine, valproic acid and benzodiazepines are eliminated so rapidly that a therapeutic value cannot be expected. In cats, phenytoin, phenobarbital, valproic acid and diazepam must be regarded as suited for chronic treatment, but there is a definite lack of clinical experience. Phenobarbital and primidone are useful for treatment of clonic-tonic generalized seizures (grand mal) in dogs. The effect of primidone depends mostly on its metabolite phenobarbital. Since primidone, given in high dosage for longer periods of time, gives rise to liver damage, phenobarbital is regarded as the drug of first choice. A status epilepticus may be treated by i.v. injection of diazepam, clonazepam, phenytoin or lidocaine. In cats with grand mal, treatment with daily doses of about 1 mg/kg diazepam may be tried. It proved effective for longer time periods without development of tolerance. There is no reliable clinical experience with other drugs in this species.
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PMID:[Pharmacologic principles in the treatment of epilepsy in the dog and cat]. 383 46

One-third of Wistar rats bred in our laboratory present recurrent seizures whose EEG and clinical symptomatology resemble those of human petit mal. Bilateral cortical synchronous spike- and wave discharges (7-11 c/s; 200-600 microV, lasting 0.5 to 40 s) accompany behavioral arrest and are associated frequently with facial myoclonia. These seizures, observed as long as the animals survive, appear spontaneously and seem to be unrelated to surgical procedures. Antiepileptics in common clinical use were tested. Ethosuximide (greater than 12.5 mg/kg), diazepam (greater than 0.5 mg/kg), trimethadione and sodium valproate (greater than 50 mg/kg) suppressed these discharges in a dose related manner. Carbamazepine and phenytoin were ineffective or aggravated the seizures. Phenobarbital, effective at 2.5 to 10 mg/kg, was ineffective at 20 mg/kg. The similar effects of these antiepileptics on both the rats' seizures and human petit mal confirm the hypothesis that this phenomenon constitutes a valid pharmacological model of petit mal epilepsy. Its predictive value appears to be superior to that of other currently used models.
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PMID:Antiepileptic drug evaluation in a new animal model: spontaneous petit mal epilepsy in the rat. 392 81

The intellectual functions of 64 epileptic patients who had had an initial evaluation between five and 16 years of age, including the WISC, were re-evaluated after a period of at least five years. In general the seizure states had improved, and 50 per cent were in remission for between two and eight years. All but four were still taking at least one anticonvulsant drug. WISC IQ estimates showed a slight decrease. Verbal and performance areas could be differentially affected, and a gain in one could be offset by a loss in the other, so the Full-scale IQ might not be a reliable measure of day-to-day performance. Those whose seizures remained uncontrolled had a statistically significant decrease in performance IQ, whereas in general it was stable or increased for patients in remission. There was evidence that decreased IQ indicated slower mental growth rather than loss of previously acquired function. Phenobarbital but not phenytoin levels were inversely correlated with IQ, suggesting that the upper limit of the 'therapeutic range' of phenobarbital may already be toxic with regard to learning abilities. To optimize an epileptic child's functioning in school and to prevent long-term intellectual problems, it is advisable that IQ testing should be part of the routine initial evaluation, and that drug levels should be checked at regular intervals.
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PMID:Intellectual functions of patients with childhood-onset epilepsy. 394 82

A series of 6-aryl-3-(hydroxypolymethyleneamino)pyridazines derivatives was synthesized and evaluated for anticonvulsant activity. The compounds were screened in mice for their ability to antagonize maximal electroshock- and bicuculline-induced seizures; neurotoxicity was evaluated in the rotorod test. The anticonvulsant activity of the most potent compounds in this series was also examined in kindled amygdaloid rats and in photoepileptic Papio papio baboons. Phenobarbital, diphenylhydantoin, carbamazepine, and sodium valproate were used as standard antiepileptic drugs. The structure-activity relationships in this series were examined by either varying the aryl ring in the 6-position of the pyridazine ring or by modifying the 3-amino side chain. Only the compounds with a phenyl ring in the 6-position of the pyridazine ring exhibited appreciable anticonvulsant activity. Furthermore, a 4-hydroxypiperidine side chain in the 3-position of the pyridazine ring appeared essential for anticonvulsant activity. Substituting the phenyl ring with a Cl in the 2-position led to a substantial increase of activity; disubstituting the phenyl ring with a Cl in the 2- and 4-positions yielded the most potent compounds in this series, some of which were as potent or more potent than phenobarbital. Two compounds, 6-(2-chlorophenyl)-3-(4-hydroxypiperidino)pyridazine (2) and 6-(2,4-dichlorophenyl)-3-(4-hydroxypiperidino)pyridazine (3), were selected for further studies. Clinical evaluation of these compounds is in progress.
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PMID:Synthesis and activity of 6-aryl-3-(hydroxypolymethyleneamino)pyridazines in animal models of epilepsy. 395 Sep 16

The efficacy of phenobarbital and primidone against canine epilepsy was compared in a controlled study. Thirty-five dogs showing generalized tonic-clonic seizures (grand mal), treated for a minimum of 6 months, were included in the study; fifteen of these were treated with phenobarbital, the other twenty with primidone. Both drugs were dosed according to the clinical requirement; the daily doses ranged from 5-17 mg/kg phenobarbital and from 17-70 mg/kg primidone. The plasma concentrations of phenobarbital, or of primidone and its metabolites phenobarbital and phenylethylmalondiamide (PEMA), were routinely monitored. Complete control of tonic-clonic seizures for 6 months, at least, was attained in six out of fifteen dogs of the phenobarbital group, and in five out of twenty dogs in the primidone group. A further six dogs on phenobarbital, and seven dogs on primidone, were classified as 'improved', i.e. the rate of seizures was reduced by at least 50%. The rest of the dogs were not improved by the treatment. The difference between the efficacy of phenobarbital and primidone was not significant, but primidone gave rise to signs of liver toxicity in fourteen out of twenty dogs, as indicated by considerable elevations of liver enzyme values (alanine transferase, glutamate dehydrogenase, alkaline phosphatase). Phenobarbital is, therefore, regarded as the drug of first choice for the treatment of canine epilepsy.
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PMID:Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison. 402 Sep 42

This study was designed to determine the effectiveness of clonidine (CL) and CL analogue, lofexidine (LF), in reducing the incidence and/or severity of convulsion associated with barbiturate withdrawal in mice. CL and LF have been shown to be useful in blocking opioid withdrawal symptoms in rodents and man. Some of the symptoms and possibly the mechanism(s) of the barbiturate withdrawal syndrome are similar to those of the opioid withdrawal syndrome. Therefore, we hypothesized that LF and CL may be efficacious in treating barbiturate withdrawal. The method of Belknap et al as modified by Blum et al for inducing barbiturate dependence in mice was used. Phenobarbital was thoroughly mixed with the animals' milled diet. After 10 days 45 pre-treated mice were divided into withdrawal, control, clonidine- and lofexidine-treated groups. Withdrawal scores were graded as 0 = no effect, 1 = tremor, 2 = wild running, 3 = tonic-clonic seizures, 4 = death, and were collected for each group every 5 hr for 2.5 days. The data in this model suggest that CL and LF offer no protective effect in treating barbiturate withdrawal-induced seizures in mice.
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PMID:Investigation of clonidine and lofexidine for the treatment of barbiturate withdrawal in mice. 408 62


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