potassium-bromide and Epilepsy

In women with epilepsy, seizures can be influenced by variations in sex hormone secretion during the menstrual cycle. The proconvulsant effects of estrogen have been demonstrated in both animals and humans, whereas progesterone has been found to have anticonvulsant properties. Catamenial epilepsy affects approximately one-third of women with epilepsy. This type of epilepsy has generally been defined as an increase in seizure frequency beginning immediately before or during menses. However, three distinct patterns of catamenial epilepsy have been described: perimenstrual, periovulatory, and luteal. The diagnosis of catamenial epilepsy can be made through careful assessment of menstrual and seizure diaries and characterization of cycle type and duration. A variety of therapies for catamenial epilepsy have been proposed, including acetazolamide, cyclical use of benzodiazepines or conventional antiepileptic drugs (AEDs), and hormonal therapy. However, evidence for the effectiveness of these treatment approaches comes from small, unblinded series or anecdotal reports. Larger multicenter trials, as well as further investigation of the pathophysiology of the disorder, are needed to identify the most effective treatment for women with catamenial epilepsy.

Topics: Acetazolamide; Adolescent; Adult; Animals; Anticonvulsants; Brain Edema; Bromides; Contraceptives, Oral, Hormonal; Convulsants; Epilepsy; Estradiol; Estrogen Receptor Modulators; Female; Gonadal Steroid Hormones; Humans; Incidence; Menstrual Cycle; Middle Aged; Models, Biological; Periodicity; Potassium Compounds; Pregnanolone; Progesterone; Pyramidal Cells; Rats; Seizures

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Drug Monitoring; Epilepsy; Food-Drug Interactions; Phenobarbital; Potassium Compounds

Successful treatment of seizure disorders in small animals requires proper patient assessment, understanding the principles of antiepileptic drug (AED) therapy, designing a strategy for pharmacotherapy, and plans for emergency treatment. Several levels of assessment are needed in managing an epileptic patient to include the diagnosis, effectiveness of therapy, and health-related quality of life assessments. Three levels of diagnosis are important in determining the appropriate AED therapy: 1) confirmation that an epileptic seizure has occurred, and if so, the seizure type(s) manifested; 2) diagnosis of the seizure etiology; and 3) determination of an epileptic syndrome. Monotherapy is the initial goal of treating any cat or dog with epilepsy to reduce possible drug-drug interactions and adverse effects. Unfortunately, many of the AEDs useful in people cannot be prescribed to small animals either due to inappropriate pharmacokinetics (too rapid of an elimination), and potential hepatotoxicity. Thus, the most commonly used AEDs in veterinary medicine are from the same mechanistic category, that of enhancing inhibition of the brain. Antiepileptic drugs can be classified into three broad mechanistic categories: 1) enhancement of inhibitory processes via facilitated action of gamma amino-butyric acid (GABA); 2) reduction of excitatory transmission; and 3) modulation of membrane cation conductance. Pharmacotherapy strategies should be designed based on the decision when to start treatment, choice of the appropriate AED, and proper AED monitoring and adjustment. Information is presented for the current AEDs of choice, phenobarbital and bromide. Additional guidelines are provided for administration of newer AEDs, felbamate and gabapentin. All owners should be aware that emergency therapy may be necessary if recurrent or severe seizures occur in their pet. A rapid, reliable protocol is presented for the emergency management of seizuring cats and dogs in the hospital and at home. Home treatment with per rectal administration of diazepam in the dog has proven to be an effective means of reducing seizure frequency and owner anxiety. Treating each animal as an individual, applying the philosophy that seizure prevention is better than intervention, and consulting specialists to help formulate or revise treatment plans will lead to improved success in treating seizure disorders in the cat and dog.

Topics: Acetates; Amines; Animals; Anticonvulsants; Bromides; Cat Diseases; Cats; Cyclohexanecarboxylic Acids; Diazepam; Dog Diseases; Dogs; Drug Resistance; Emergency Treatment; Epilepsy; Felbamate; Gabapentin; gamma-Aminobutyric Acid; Phenobarbital; Phenylcarbamates; Potassium Compounds; Propylene Glycols; Seizures

Imepitoin has recently been approved in Europe for the management of dogs with idiopathic epilepsy. Currently, there is no evidence-based information available on the efficacy of antiepileptic drugs used as additions to the therapeutic regimen in dogs with idiopathic epilepsy that are not well controlled with imepitoin. The goal of this study was to evaluate the efficacy of phenobarbital or potassium bromide (KBr) as add-on antiepileptic drugs for controlling dogs refractory to a maximum dose of imepitoin (30 mg/kg twice daily). The study was performed as a prospective, randomised, controlled clinical trial. The efficacy of phenobarbital and KBr was evaluated by comparing monthly seizure frequency (MSF), monthly seizure day frequency (MSDF), the presence of cluster seizures during a retrospective 2-month period with a prospective follow-up of 6 months, and the overall responder rate. Twenty-seven dogs were included in the study, 14 dogs in the phenobarbital group and 13 dogs in the KBr group. Both median MSF and MSDF decreased in the phenobarbital group (both P = 0.001) and in the KBr group (P = 0.004 and P = 0.003, respectively). Overall, the number of dogs with cluster seizures decreased (P = 0.0005). The responder rate was 79% vs. 69% in the phenobarbital and KBr groups, respectively. We conclude that phenobarbital or KBr add-on treatment decreases median MSF and MSDF in epileptic dogs refractory to a maximum dose of imepitoin. Combination therapy was generally well tolerated and resulted in an improvement in seizure management in the majority of the dogs.

Topics: Animals; Anticonvulsants; Belgium; Bromides; Dog Diseases; Dogs; Epilepsy; Imidazoles; Phenobarbital; Potassium Compounds; Prospective Studies; Retrospective Studies; Seizures

Despite appropriate antiepileptic drug treatment, approximately one-third of humans and dogs with epilepsy continue experiencing seizures, emphasising the importance for new treatment strategies to improve the quality of life of people or dogs with epilepsy. A 6-month prospective, randomised, double-blinded, placebo-controlled cross-over dietary trial was designed to compare a ketogenic medium-chain TAG diet (MCTD) with a standardised placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy. Dogs were fed either MCTD or placebo diet for 3 months followed by a subsequent respective switch of diet for a further 3 months. Seizure frequency, clinical and laboratory data were collected and evaluated for twenty-one dogs completing the study. Seizure frequency was significantly lower when dogs were fed the MCTD (2·31/month, 0-9·89/month) in comparison with the placebo diet (2·67/month, 0·33-22·92/month, P=0·020); three dogs achieved seizure freedom, seven additional dogs had ≥50 % reduction in seizure frequency, five had an overall <50 % reduction in seizures (38·87 %, 35·68-43·27 %) and six showed no response. Seizure day frequency were also significantly lower when dogs were fed the MCTD (1·63/month, 0-7·58/month) in comparison with the placebo diet (1·69/month, 0·33-13·82/month, P=0·022). Consumption of the MCTD also resulted in significant elevation of blood β-hydroxybutyrate concentrations in comparison with placebo diet (0·071 (sd 0·035) v. 0·053 (sd 0·028) mmol/l, P=0·028). There were no significant changes in serum concentrations of glucose (P=0·903), phenobarbital (P=0·422), potassium bromide (P=0·404) and weight (P=0·300) between diet groups. In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment.

Topics: 3-Hydroxybutyric Acid; Animals; Anticonvulsants; Blood Glucose; Bromides; Cross-Over Studies; Diet, Ketogenic; Dogs; Double-Blind Method; Epilepsy; Female; Male; Phenobarbital; Potassium Compounds; Prospective Studies; Quality of Life; Seizures; Treatment Outcome; Triglycerides

To assess tolerability and short-term efficacy of oral administration of pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with poorly controlled suspected idiopathic epilepsy.. Open-label, noncomparative clinical trial.. 11 client-owned dogs suspected of having idiopathic epilepsy that was inadequately controlled with phenobarbital, potassium bromide, or a combination of these 2 drugs.. Dogs were treated with pregabalin (3 to 4 mg/kg [1.4 to 1.8 mg/lb], PO, q 8 h) for 3 months. Number of generalized seizures in the 3 months before and after initiation of pregabalin treatment was recorded. Number of responders (>or= 50% reduction in seizure frequency) was recorded, and seizure frequency before and after initiation of pregabalin treatment was compared by use of a nonparametric Wilcoxon signed rank test.. Seizures were significantly reduced (mean, 57%; median, 50%) after pregabalin administration in the 9 dogs that completed the study; 7 were considered responders with mean and median seizure reductions of 64% and 58%, respectively. Adverse effects for pregabalin were reported in 10 dogs. Mean and median plasma pregabalin concentrations for all dogs were 6.4 and 7.3 microg/mL, respectively.. Pregabalin may hold promise as a safe and effective adjunct anticonvulsant drug for epileptic dogs poorly controlled with the standard drugs phenobarbital or potassium bromide. Adverse effects of pregabalin appeared to be mild. Additional studies with larger numbers of dogs and longer follow-up intervals are warranted.

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Female; gamma-Aminobutyric Acid; Male; Phenobarbital; Potassium Compounds; Pregabalin

Topics: Adolescent; Anticonvulsants; Bromides; Bromine; Child; Child, Preschool; Chlorine; Drug Monitoring; Epilepsy; Female; Humans; Infant; Male; Potassium Compounds

Bromide is a halide ion of the element bromine usually administered in the form of potassium salt as monotherapy or add-on treatment in epileptic dogs. It is excreted unchanged in the urine and undergoes tubular reabsorption in competition with chloride. Thus, dietary chloride content affects serum bromide concentrations. This is the first published clinical report of bromide toxicosis secondary to a dietary modification of chloride content in an epileptic dog treated with potassium bromide.. A 3-year-old 55-kg neutered male Tibetan Mastiff was evaluated because of a 1-month history of progressive signs including ataxia, lethargy and behaviour changes. The dog was successfully treated for idiopathic epilepsy since the age of 1-year-old with phenobarbital and potassium bromide. Two months prior to presentation, the owners decided to change the dog's diet without veterinary advice. Physical examination was unremarkable. A 12-kg weight gain was recorded since last follow-up (8 months). Neurological examination revealed severe symmetric 4-limbs ataxia with altered vigilance and intermittent episodes of hyperactivity and aggressive behaviour without significant abnormality of cranial nerves. Serum bromide concentration was high and increased by 103 % since last follow-up. Nutritional evaluation revealed a 53 % decrease of chloride content in the diet before and after dietary transition. Bromide toxicosis was suspected, due to bromide reduced clearance secondary to the decreased dietary chloride content. Potassium bromide treatment was lowered by 15 % without further dietary changes. Neurologic signs progressively improved over the next month, without any seizure. After two months, the serum bromide concentration lowered to the same level measured before dietary modification. After four months, neurological examination was unremarkable.. Dietary chloride content can directly influence serum bromide concentrations, therefore affecting seizure control or contributing to unexpected adverse effects. In the present case, a reduction in chloride intake markedly increased serum bromide concentrations causing bromism. Dietary changes should be avoided in dogs treated with potassium bromide to maintain stable serum bromide levels.

Topics: Animals; Anticonvulsants; Bromides; Chlorides; Diet; Dog Diseases; Dogs; Epilepsy; Male; Potassium Compounds

Topics: Adult; Anticonvulsants; Bromides; Dermatitis, Exfoliative; Drug Eruptions; Epilepsy; Female; Humans; Potassium Compounds

Topics: Anticonvulsants; Bromides; Child, Preschool; Drug Therapy, Combination; Electroencephalography; Epilepsy; Fatal Outcome; Humans; Infant; Male; Mutation; Nerve Tissue Proteins; Phenobarbital; Potassium Channels, Sodium-Activated; Potassium Compounds; Treatment Outcome

Phenobarbital or potassium bromide (KBr) add-on treatment decreases the average monthly seizure frequency in dogs with idiopathic epilepsy resistant to a maximum dose of imepitoin. The importance of continued administration of imepitoin in these dogs is currently unknown. The goal of this study was to assess whether imepitoin withdrawal would destabilize epileptic seizure control. In this prospective clinical trial epileptic seizure control was evaluated by comparing the monthly seizure frequency of 13 dogs with well-controlled idiopathic epilepsy receiving a combination of imepitoin and phenobarbital (n=4), imepitoin and KBr (n=7), and imepitoin, phenobarbital and KBr (n=2) during a period of 3-6 months (pre-withdrawal period), with a follow-up period of 9-12 months after withdrawal of imepitoin (post-withdrawal period). Adverse effects were also recorded before and after withdrawal of imepitoin. Imepitoin was tapered off over 3 months as follows: 20mg/kg twice daily for 1 month, then 10mg/kg twice daily for 1 month, then once daily for 1 month. Withdrawal of imepitoin did not increase monthly seizure frequency (P=0.9). Moreover, all owners reported improvement in the adverse effects experienced by their dog after withdrawal of imepitoin. Imepitoin withdrawal in epileptic dogs that were well-controlled with imepitoin and phenobarbital and/or KBr did not worsen epileptic seizure control, and possibly decreased antiepileptic treatment-related adverse effects. However, a worsening of seizure frequency could occur in individual cases.

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Female; Imidazoles; Male; Phenobarbital; Potassium Compounds; Seizures; Treatment Outcome

A girl with mild psychomotor developmental delay developed right or left hemiclonic convulsion at 10months of age. One month later, clusters of hemiclonic or bilateral tonic seizures with eyelid twitching emerged, resulting in status epilepticus. Treatment with phenobarbital and potassium bromide completely terminated the seizures within 10days. Ictal electroencephalography revealed a migrating focus of rhythmic 3-4Hz waves from the right temporal to right frontal regions and then to the left frontal regions. Genetic analysis was conducted based on the characteristic facial appearance of the patient, which identified a 2.1-Mb terminal deletion on chromosome 4p. This is the first case of Wolf-Hirschhorn syndrome complicated by epilepsy with migrating partial seizures.

Topics: Anticonvulsants; Brain; Bromides; Chromosome Deletion; Chromosomes, Human, Pair 4; Comparative Genomic Hybridization; Electroencephalography; Epilepsy; Female; Humans; Infant; Phenobarbital; Potassium Compounds; Seizures; Wolf-Hirschhorn Syndrome

Animals treated with anticonvulsant drugs may have increased canine pancreas-specific lipase (cPLI) values. Inflammatory conditions and specifically acute pancreatitis are of major concern in these animals. Elevation in C-reactive protein is being associated with inflammatory status in dogs and it has been correlated with the clinical severity of pancreatitis. In the present study, we investigated if there is a correlation between the cPLI increase, changes in C-reactive protein and hepatic enzymes, as well as the incidence of severe acute pancreatitis (AP) in dogs with anticonvulsant treatment (phenobarbital, or potassium bromide or both). Increased values of pancreas-specific lipase were found in 6.8% of the animals in treatment with anticonvulsants, and this increase is correlated with the increase in triglycerides, alkaline phosphatase, and alanine aminotransferase but not with C-reactive protein levels, which suggests a possible induction or release phenomenon rather than a clear severe AP. C-reactive protein levels did not affect cPLI values on the population studied. Only 2 animals had clinical and analytical data suggestive of AP, indicating a low prevalence (0.6%). In conclusion, cPLI may be increased in a low percentage of animals with anticonvulsants treatment and its increase may not be associated with severe AP. It may be induced by the anticonvulsants drugs; however, further studies are advised to rule out other possible causes that increased cPLI.

Topics: Animals; Anticonvulsants; Bromides; C-Reactive Protein; Dog Diseases; Dogs; Epilepsy; Female; Lipase; Male; Pancreas; Pancreatitis; Phenobarbital; Potassium Compounds

To determine serum bromide concentrations following an oral loading dose in dogs.. Retrospective review of clinical records of dogs suffering from seizures that were treated with bromide. A loading dose of 600 mg/kg potassium bromide was administered orally in 17 to 48 hours together with a maintenance dose of 30 mg/kg/day. Blood samples were collected within 24 hours after completing the protocol and serum bromide concentrations were determined by ultra-violet gold chloride colorimetric assay.. Thirty-eight dogs were included in the study. The median age was 3 (range, 0 · 2 to 10) years and bodyweight 21 · 8 (3 · 45 to 46 · 2) kg. The median serum bromide concentration was 1 · 26 (0 · 74 to 3 · 6) mg/mL. Thirty-two dogs (84 · 2%) had serum bromide concentrations within the therapeutic interval (1 to 3 mg/mL). The serum concentration in five dogs (13 · 2%) was just under the minimal therapeutic value and in one dog (2 · 6%) it exceeded the maximal therapeutic value (3 · 6 mg/mL).. Following this oral loading dose protocol, serum bromide concentrations reach the therapeutic range in the majority of dogs. This indicates that the suggested protocol is effective in achieving therapeutic concentrations rapidly in epileptic dogs.

Topics: Administration, Oral; Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Epilepsy; Potassium Compounds; Retrospective Studies

On 12 May 1857, Edward Sieveking read a paper on epilepsy to the Royal Medical and Chirurgical Society in London. During the discussion that followed Sir Charles Locock, obstetrician to Queen Victoria, was reported to have commented that during the past 14 months he had used potassium bromide to successfully stop epileptic seizures in all but one of 14 or 15 women with 'hysterical' or catamenial epilepsy. This report of Locock's comment has generally given him credit for introducing the first reasonably effective antiepileptic drug into medical practice. However examination of the original reports raises questions as to how soundly based the accounts of Locock's comments were. Subsequently, others using the drug to treat epilepsy failed to obtain the degree of benefit that the reports of Locock's comments would have led them to expect. The drug might not have come into more widespread use as a result, had not Samuel Wilks provided good, independent evidence for the drug's antiepileptic efficacy in 1861.

Topics: Anticonvulsants; Bromides; Epilepsy; Female; History, 19th Century; Humans; Obstetrics; Potassium Compounds; United Kingdom

To evaluate clinical signs, risk factors, and outcomes associated with bromide toxicosis (bromism) in dogs with idiopathic epilepsy treated with potassium or sodium bromide.. Retrospective case-control study.. 83 clinically ill epileptic dogs with (cases; n = 31) and without (controls; 52) bromism.. Medical records were reviewed for information regarding signalment, epilepsy history, treatment, diet, clinicopathologic test results, concurrent diseases, clinical signs, and outcome. Case and control dogs were matched by the veterinary hospitals from which they were referred and by month of admission. A presumptive diagnosis of bromism was made in case dogs when treatment for primary clinical signs was limited to induction of diuresis or reduction in the dose of bromide administered, and this diagnosis was supported by serum bromide concentrations. Potential risk factors for bromism were identified via univariate and subsequent multivariate logistic regression analyses.. Common clinical signs of bromism included alterations in consciousness, ataxia, and upper and lower motor neuron tetraparesis and paraparesis. The multivariate analysis identified bromide dose at admission to the hospital as the only factor significantly associated with bromism. In all dogs with bromism, treatment via dose reduction or facilitated renal excretion of bromide resulted in rapid clinical improvement, although breakthrough seizures happened during treatment in 8 of 31 (26%) dogs.. Bromism is a clinically heterogeneous, dose-dependent neurotoxicosis that is largely reversible with treatment. Regular serial monitoring of serum bromide concentrations is recommended to optimize anticonvulsant treatment in dogs with idiopathic epilepsy.

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Epilepsy; Potassium Compounds; Retrospective Studies; Risk Factors; Sodium Compounds

To identify veterinarians' approaches and concerns when managing canine and feline patients with acute and chronic seizure disorders.. Cross-sectional survey.. A questionnaire was distributed to veterinarians to determine how many dogs and cats they were actively treating for seizures, their anticonvulsant drug (ACD) preferences for treating acute and chronic seizure disorders and whether serum anticonvulsant concentrations and/or biochemical analytes were routinely measured. Additional questions involved the respondent's year and place of graduation and identified concerns they faced when managing patients with seizure disorders.. Phenobarbitone was the most commonly used ACD for managing chronic seizure disorders in both dogs and cats, with 82% of respondents using a combination of phenobarbitone and potassium bromide to manage refractory seizure disorders in dogs. Most respondents (96%) felt comfortable managing seizures in dogs, but only 63% were comfortable managing affected cats. Routine monitoring of serum ACD concentrations and of liver biochemical analytes was performed routinely by 71% and 45% of respondents, respectively. Of the respondents, 86% graduated from Australian universities and of these 53% had graduated after 1985.. Veterinarians identified when to commence medication, whether regular monitoring of serum ACD concentrations and liver enzyme activity was necessary, and if the cost was justified. Veterinarians also identified the need to balance dose rates and side-effects by using combination therapy, and the importance of providing accurate information to clients about what to expect in terms of seizure control for their pet.

Topics: Animals; Anticonvulsants; Bromides; Cat Diseases; Cats; Cross-Sectional Studies; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Humans; Liver; Phenobarbital; Potassium Compounds; Surveys and Questionnaires; Veterinarians

A new ion chromatographic procedure has been developed and validated for the determination of bromide in canine plasma. Following a simple dilution, samples were separated on a Metrosep A Supp 5 column. The mobile phase was an isocratic mixture of 2.2 mM Na(2)CO(3), 1.0 mM NaHCO(3), and 1% acetonitrile, with a flow-rate of 0.7 ml/min. The procedure produced a linear curve over the concentration range of 50-2500 microg/ml. The development of the assay permitted the determination of therapeutic levels after oral administration of potassium bromide to dogs being treated for epilepsy.

Topics: Administration, Oral; Animals; Anticonvulsants; Bromides; Chromatography, Ion Exchange; Dog Diseases; Dogs; Epilepsy; Potassium Compounds

To compare serum triglyceride concentrations obtained after food had been withheld (i.e., fasting concentrations) in dogs with epilepsy that had been treated long term (> or = 3 months) with phenobarbital or with phenobarbital and potassium bromide with concentrations in healthy control dogs.. Cross-sectional study.. 57 epileptic dogs that had been treated with phenobarbital (n=28) or with phenobarbital and bromide (29) and 57 healthy, untreated control dogs matched on the basis of age, breed, sex, neuter status, and body condition score.. Blood samples were collected after food had been withheld for at least 12 hours, and serum biochemical and lipid concentrations were determined. Oral fat tolerance tests were performed in 15 control dogs and 9 dogs with epilepsy treated with phenobarbital alone.. 19 of the 57 (33%) epileptic dogs had fasting serum triglyceride concentrations greater than the upper reference limit. Nine (16%) dogs had a history of pancreatitis, and 5 of the 9 had high fasting serum triglyceride concentrations at the time of the study. A significant relationship was found between body condition score and fasting serum triglyceride concentration in all dogs, but serum triglyceride concentration was not significantly associated with phenobarbital dosage or serum phenobarbital concentration.. Results suggested that dogs treated long term with phenobarbital or with phenobarbital and bromide may develop hypertriglyceridemia. Fasting serum triglyceride concentration should be periodically monitored in dogs treated with phenobarbital because hypertriglyceridemia is a risk factor for pancreatitis.

Topics: Animals; Bromides; Case-Control Studies; Cross-Sectional Studies; Dog Diseases; Dogs; Epilepsy; Fasting; Female; Hypertriglyceridemia; Male; Pancreatitis; Phenobarbital; Potassium Compounds; Risk Factors; Triglycerides

Sir Samuel Wilks, sometime Physician to Guy's Hospital and President of the Royal College of Physicians (1896-99), was regarded as the leading British scientific physician of his day. His contributions to gastroenterology, cardiology and clinical science in general have been emphasized in recent times. He also recognized that syphilis affected the internal organs as well as the skin. In 1866 he realised that epileptogenesis occurred in the cerebral cortex: independently of Sir Charles Locock (1799-1875), he discovered the antiepileptic properties of potassium bromide. He provided possibly the first account of alcoholic peripheral neuritis and published an early account of probable myasthenia gravis.

Topics: Bromides; Epilepsy; Family Practice; History, 19th Century; History, 20th Century; Humans; Nervous System Diseases; Neurology; Potassium Compounds; Societies, Medical; United Kingdom

Topics: Anticonvulsants; Bromides; Epilepsy; History, 19th Century; Humans; Potassium Compounds

Potassium bromide is still in use for the treatment of multidrug-resistant seizures. It is a known cause of severe drug-induced skin disorders. The clinical presentation of bromoderma may be similar to that of pyoderma gangrenosum when occurring with a single lesion. The case of a young girl with a single vegetating plaque of bromoderma on the leg is reported. The presence of pustules at the periphery of the plaque provides the clinical clue to the diagnosis.

Topics: Bromides; Child; Epilepsy; Female; Humans; Potassium Compounds; Pyoderma

Topics: Anticonvulsants; Brain Injuries; Bromides; Crime; Epilepsy; History, 19th Century; Humans; Male; Potassium Compounds; Sleep Wake Disorders; Wounds, Gunshot

To explore seizure management from the perspective of the owners of dogs with idiopathic epilepsy.. Questionnaires were mailed to owners of 29 dogs under management for suspected or diagnosed idiopathic epilepsy through the clinics of the Small Animal Hospital of the University of Glasgow Veterinary School, using either phenobarbitone or potassium bromide alone or in combination.. The postal survey had an 86 per cent response rate. Analysis of the responses demonstrated that "the dog's quality of life", "adequate seizure frequency" and "acceptable side effects of antiepileptic drugs" were the three greatest concerns for owners; 52 per cent of owners strongly agreed that the seizure management for their dog was adequate, though the seizure frequency reported varied within this group; the majority of owners did not consider the administration of medication a nuisance. However, approximately 60 per cent of owners reported that caring for an epileptic dog had an effect on the organisation of their free time, though this was not dependent on perception of seizure control. Opinions as to the value of further diagnostic procedures, in particular intracranial imaging, were significantly affected by having pet health insurance.. From the owners' perspective, adequacy of seizure control is determined by the balance between "the dog's quality of life", "adequate seizure frequency" and "acceptable side effects of antiepileptic drugs". A frequency of less than one seizure every three months is associated with the perception by owners of adequate seizure control.

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Phenobarbital; Potassium Compounds; Quality of Life; Seizures; Surveys and Questionnaires; Treatment Outcome

To assess whether there is a change in seizure activity in dogs with refractory epilepsy that are receiving appropriate doses of phenobarbitone and/or potassium bromide, when gabapentin is added to the therapeutic regimen.. A prospective study of 17 dogs with a refractory seizure disorder, 16 of which have idiopathic epilepsy.. Patients were stabilised using phenobarbitone and/or potassium bromide to produce tolerable therapeutic serum concentrations and dosed additionally with gabapentin at 35 to 50 mg/kg/d (divided twice or three times daily) for 4 months. Owners recorded seizure activity and side effects during this period in a standardised diary. Patients underwent monthly physical examinations and venepuncture to assess selected serum biochemical analytes, as well as phenobarbitone and bromide concentrations. Patients were further monitored for long-term response to adjunctive gabapentin therapy.. There was no significant decrease in the number of seizures over the study period for the entire cohort, however three dogs stopped seizuring completely. There was a significant increase in the number of patients who showed an increase in the interictal period (P > 0.001). Serum alkaline phosphatase activity and triglyceride concentrations were elevated at baseline. There were no significant changes in biochemical analytes during the course of the study period. Side effects observed initially on addition of gabapentin included sedation and hind limb ataxia. The former resolved spontaneously after a few days; the latter after a slight reduction in bromide dose. Long-term, a further two patients became seizure free and ten patients remained on gabapentin indefinitely. No long-term side effects have become apparent.. Addition of gabapentin to phenobarbitone and/or potassium bromide increased the interictal period and shortened the post-seizure recovery in some canine epileptics. In some dogs, seizures were prevented completely, while in others there was an increase in interictal period. The short-half life of gabapentin has advantages for seizure control, however its present high cost may prohibit therapy in large dogs.

Topics: Amines; Animals; Anticonvulsants; Bromides; Chemotherapy, Adjuvant; Cyclohexanecarboxylic Acids; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Female; Gabapentin; gamma-Aminobutyric Acid; Male; Phenobarbital; Potassium Compounds; Prospective Studies; Seizures; Treatment Outcome

Ataxia, sedation, amnesia, ethanol and barbiturate potentiation, loss of efficacy (tolerance), development of dependence, and the potential for drug abuse limit the clinical use of benzodiazepines (BZDs) for long-term treatment of epilepsy or anxiety. BZD ligands that are in current use act as full allosteric modulators of gamma-aminobutyric acid (GABA)-gated chloride channels and, on long-term administration, trigger a functional uncoupling between the GABAA and BZD recognition sites. Partial allosteric modulators, which have a low intrinsic activity at the BZD recognition site of the GABAA receptor, might eventually overcome the limitations of full agonists such as diazepam (DZP).. In the present study, the new low-affinity partial BZD-receptor agonist ELB 138 [former name AWD 131-138; 1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one] was evaluated in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures.. ELB 138 was shown to increase potently the pentylenetetrazole (PTZ) seizure threshold in dogs. Prolonged oral administration with twice-daily dosing of ELB 138 with either 5 or 40 mg/kg over a 5-week period was not associated with loss of anticonvulsant efficacy in the PTZ dog model. To study whether physical dependence developed during long-term treatment, the BZD antagonist flumazenil was injected after 5 weeks of treatment with ELB 138. Compared with prolonged treatment with DZP, only relatively mild abstinence symptoms were precipitated in dogs treated with ELB 138, particularly at the lower dosage (5 mg/kg, b.i.d.). In a prospective trial in dogs with newly diagnosed epilepsy, ELB 138 markedly reduced seizure frequency and severity without significant difference to standard treatments (phenobarbital or primidone) but was much better tolerated than the standard drugs. In dogs with chronic epilepsy, most dogs exhibited a reduction in seizure frequency and severity during add-on treatment with ELB 138.. The data demonstrate that the partial BZD receptor agonist ELB 138 exerts significant anticonvulsant efficacy without tolerance in a dog seizure model as well as in epileptic dogs with spontaneously recurrent seizures. These data thus substantiate that partial agonism at the BZD site of GABAA receptors offers advantages versus full agonism and constitutes a valuable approach for treatment of seizures.

Topics: Animals; Anticonvulsants; Bromides; Chronic Disease; Disease Models, Animal; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Flumazenil; GABA Agonists; GABA-A Receptor Agonists; Imidazoles; Pentylenetetrazole; Phenobarbital; Potassium Compounds; Primidone; Receptors, GABA-A; Seizures; Substance Withdrawal Syndrome; Treatment Outcome

A 3-year-old Japanese girl with severe epilepsy had been treated with potassium bromide since August 1999. The dose of potassium bromide was increased from 0.5 g/day to 0.8 g/day in May 2000 because of poor control of epilepsy. She also presented high fever, caused by bacterial pneumonia, in the same period. On June 11, a reddish eruption suddenly appeared on her back. Physical examination revealed grain-size, dark-red, erythematous papules and pustules on the back and face (Fig. 1). Some of the lesions on the back were ovoid to circular with small pustules and necrotic centers. Although some papules seemed to have dell in their centers, showing the appearance of herpes virus infection, Tzanck test was negative. A biopsy specimen obtained from one of the papules revealed a massive infiltration of eosinophils and neutrophils, forming an abscess in the epidermis and dermis (Fig. 2). The serum bromide level, which was 43.7 mEq/L (normal, 0-5 mEq/L) on May 25, increased to 114 mEq/L on June 14. The eruption disappeared within 10 days after the withdrawal of potassium bromide and treatment with topical sulfadiazine silver cream. The serum bromide decreased to 56.8 mEq/L on July 6.

Topics: Anti-Infective Agents, Local; Anticonvulsants; Bromides; Child, Preschool; Dose-Response Relationship, Drug; Drug Eruptions; Epilepsy; Female; Humans; Potassium Compounds; Silver Sulfadiazine; Skin Diseases, Vesiculobullous

To establish a dosing regimen for potassium bromide and evaluate use of bromide to treat spontaneous seizures in cats.. Prospective and retrospective studies.. 7 healthy adult male cats and records of 17 cats with seizures.. Seven healthy cats were administered potassium bromide (15 mg/kg [6.8 mg/lb], p.o., q 12 h) until steady-state concentrations were reached. Serum samples for pharmacokinetic analysis were obtained weekly until bromide concentrations were not detectable. Clinical data were obtained from records of 17 treated cats.. In the prospective study, maximum serum bromide concentration was 1.1 +/- 0.2 mg/mL at 8 weeks. Mean disappearance half-life was 1.6 +/- 0.2 weeks. Steady state was achieved at a mean of 5.3 +/-1.1 weeks. No adverse effects were detected and bromide was well tolerated. In the retrospective study, administration of bromide (n = 4) or bromide and phenobarbital (3) was associated with eradication of seizures in 7 of 15 cats (serum bromide concentration range, 1.0 to 1.6 mg/mL); however, bromide administration was associated with adverse effects in 8 of 16 cats. Coughing developed in 6 of these cats, leading to euthanasia in 1 cat and discontinuation of bromide administration in 2 cats.. Therapeutic concentrations of bromide are attained within 2 weeks in cats that receive 30 mg/kg/d (13.6 mg/lb/d) orally. Although somewhat effective in seizure control, the incidence of adverse effects may not warrant routine use of bromide for control of seizures in cats.

Topics: Administration, Oral; Animals; Anticonvulsants; Bromides; Cat Diseases; Cats; Dose-Response Relationship, Drug; Epilepsy; Female; Male; Phenobarbital; Potassium Compounds; Prospective Studies; Retrospective Studies

Topics: Anticonvulsants; Bromides; England; Epilepsy; Female; History, 19th Century; Humans; Potassium Compounds

A 5-year-old boy with a peculiar type of post-encephalitic/encephalopathic epilepsy is reported. He had been healthy showing normal development before its onset. Five days after the onset of an upper respiratory infection, he had a severe generalized seizure, that evolved into intractable seizures. They were highly resistant to almost all anticonvulsants and occasionally resulted in status epilepticus. High-dose phenobarbital therapy successfully controlled the convulsions, but was discontinued because of drug-induced aplastic anemia. Alternative bromide therapy was markedly effective in controlling the seizures.

Topics: Bromides; Child, Preschool; Encephalitis; Epilepsy; Humans; Male; Potassium Compounds

In a retrospective study, at least 10% of dogs receiving potassium bromide/phenobarbital combination therapy, compared with 0.3% of dogs receiving phenobarbital monotherapy, had probable pancreatitis. Pancreatitis may be a more frequent and more serious adverse effect of potassium bromide/phenobarbital combination therapy than has been reported previously.

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Male; Pancreatitis; Phenobarbital; Potassium Compounds; Retrospective Studies

To determine whether administration of phenobarbital, potassium bromide, or both drugs concurrently was associated with abnormalities in baseline serum total thyroxine (T4), triiodothyronine (T3), free T4, or thyrotropin (thyroid-stimulating hormone; TSH) concentrations in epileptic dogs.. Prospective case series.. 78 dogs with seizure disorders that did not have any evidence of a thyroid disorder (55 treated with phenobarbital alone, 15 treated with phenobarbital and bromide, and 8 treated with bromide alone) and 150 clinically normal dogs that were not receiving any medication.. Serum total T4, total T3, free T4, and TSH concentrations, as well as serum concentrations of anticonvulsant drugs, were measured in the 78 dogs with seizure disorders. Reference ranges for hormone concentrations were established on the basis of results from the 150 clinically normal dogs.. Total and free T4 concentrations were significantly lower in dogs receiving phenobarbital (alone or with bromide), compared with concentrations in clinically normal dogs. Administration of bromide alone was not associated with low total or free T4 concentration. Total T3 and TSH concentrations did not differ among groups of dogs.. Results indicate that serum total and free T4 concentrations may be low (i.e., in the range typical for dogs with hypothyroidism) in dogs treated with phenobarbital. Serum total T3 and TSH concentrations were not changed significantly in association with phenobarbital administration. Bromide treatment was not associated with any significant change in these serum thyroid hormone concentrations.

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Female; Male; Phenobarbital; Potassium Compounds; Prospective Studies; Thyrotropin; Thyroxine; Triiodothyronine

Therapeutic drug monitoring is an underutilised resource in the management of canine primary epilepsy. Many of the anti-epileptic drugs, including phenobarbitone, have variable pharmacokinetic profiles in different dogs, with each individual animal showing variable rates of absorption, distribution, metabolism and excretion. This results in variable serum drug concentrations with the same oral dose. Many clinicians interpret this situation as therapeutic failure and classify these patients as refractory to treatment. By measuring blood concentrations of drugs at appropriate times, it is possible to explain the efficacy or failure of treatment, and also to prevent serum concentrations from reaching toxic levels. By analysing paired samples, key pharmacokinetic parameters may be calculated for each patient and a profile for the disposition of the drug obtained. Individual optimal drug dosage can be calculated for each patient at little cost to the pet owner.

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Drug Monitoring; Drug Therapy, Combination; Epilepsy; Phenobarbital; Potassium Compounds

Potassium bromide again is well known to be surprisingly effective in patients with severe myoclonic epilepsy in infants (SME). Rare side effects on the skin reappeared, such as the febrile nodular panniculitis (Weber-Christian syndrome). In 1993 we described the first three cases of necrotizing panniculitis and introduced the term 'halogen panniculitis'. It is a systemic disease with crops of subcutaneous nodules, fever, elevated sedimentation rate, hepatosplenomegalia, and abdominal pain. Later severe necrosis of the skin and adipose tissue may happen with deep ulcerations. History and course of five cases, described in this paper, suggest either an allergy or toxic reason. Histologic picture shows inflammation of adipose tissues with infiltrating lymphocytes, but lymphocyte transformation test (LTT) was not reliable in diagnosing the disease. Possibly, bromides act as a chemokine and stimulate inflammatory processes. Bromide can be transformed into a bromine radical/free electron pair under UV irradiation at 228.8 nm in aqueous solution. The bromine radical may have detrimental effects on the tissue. However, despite some research, the origin of halogen panniculitis and similar diseases remains unclear.

Topics: Adolescent; Anticonvulsants; Bromides; Child; Child, Preschool; Epilepsy; Female; Humans; Male; Panniculitis; Potassium Compounds; Recurrence; Retrospective Studies; Skin Diseases; Skin Ulcer

To determine therapeutic serum drug concentrations in epileptic dogs treated with potassium bromide.. Retrospective study.. 122 dogs with major motor epilepsy.. Medical histories were collected for epileptic dogs treated with potassium bromide with or without phenobarbital sodium or primidone, from which serum was submitted for bromide analysis from May 1992 to May 1996 to the Therapeutic Drug Monitoring Program at Cornell University's College of Veterinary Medicine. A therapeutic response (improved seizure control) was defined as a > or = 50% reduction in seizure frequency following initiation of bromide treatment. Serum bromide and phenobarbital concentrations and therapeutic outcome were determined for all dogs.. 72% of epileptic dogs had a > or = 50% reduction in seizure frequency following initiation of treatment with potassium bromide. Discontinuation of barbiturate treatment was possible in 19% of those dogs originally treated with phenobarbital or primidone. Of those dogs continued on bromide and phenobarbital, 45% maintained seizure control with serum phenobarbital concentrations < 20 micrograms/ml. Significantly higher serum bromide concentrations were required when dogs were initially or eventually treated with bromide alone (mean bromide concentration, 1,906 micrograms/ml) compared with dogs treated with potassium bromide along with a barbiturate (mean bromide concentration, 1,621 micrograms/ml).. When dogs are treated with bromide and phenobarbital, a reasonable therapeutic range for serum bromide concentrations is 810 to 2,400 micrograms/ml, and for bromide treatment alone, the range is 880 to 3,000 micrograms/ml. When phenobarbital is used in combination with bromide, a reasonable therapeutic range for serum phenobarbital concentrations is 9 to 36 micrograms/ml, although in some dogs treated with bromide, phenobarbital can eventually be discontinued.

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Follow-Up Studies; Phenobarbital; Potassium Compounds; Primidone; Retrospective Studies; Treatment Outcome

A flow injection system was constructed using a bromide-selective electrode and used to determine serum bromide in patients with epilepsy. A 10-microliter serum sample was injected into a carrier stream flowing at 0.12 ml min-1. Potential changes and bromide concentrations were linearly related in the range 3-50 mM. The lower limit of detection for serum bromide was 1 mM and this electrode sensitivity spanned the entire concentration range required for bromide therapy (9-24 mM). The results compared favourably with those obtained by colorimetry.

Topics: Autoanalysis; Bromides; Case-Control Studies; Colorimetry; Cost Control; Epilepsy; Flow Injection Analysis; Humans; Linear Models; Potassium Compounds; Potentiometry; Reference Values; Time Factors

Bromide toxicosis was diagnosed in an 8-year-old Labrador Retriever that had been treated for epilepsy with potassium bromide, at a dosage of 29 mg/kg of body weight/d. Clinical signs included hind limb weakness, ataxia, and disorientation. Renal insufficiency, diagnosed by determination of endogenous creatinine clearance, was believed to be responsible for the development of bromide toxicosis in this dog. Diuresis with physiologic saline solution and discontinuation of bromide and phenobarbital treatment resulted in rapid resolution of abnormal neurologic signs; however, serum bromide concentrations decreased dramatically during diuresis and seizures recurred. Although saline diuresis has been recommended for the treatment of bromide intoxication in human beings, more conservative measures, such as discontinuation of bromide and short-term fluid administration, may be more appropriate for epileptic dogs.

Topics: Animals; Anticonvulsants; Bromides; Creatinine; Diuresis; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Female; Half-Life; Metabolic Clearance Rate; Phenobarbital; Poisoning; Potassium Compounds; Renal Insufficiency; Sodium Chloride

Bromide treatment was successful in controlling seizures in an 11-year-old Dachshund with epilepsy and presumptive phenobarbital-associated hepatopathy. Because bromide does not induce liver enzyme activity and does not seem to be hepatotoxic, it can be used to control seizures in dogs with concurrent epilepsy and hepatic disease. In this dog, institution of a special calculolytic diet with high chloride content was associated with a decrease in serum bromide concentrations and the recurrence of seizures. High chloride intake increases the elimination of bromide in dogs, leading to higher dosage requirements for bromide in dogs fed high-chloride diets.

Topics: Animals; Anticonvulsants; Bromides; Chlorides; Diet; Dog Diseases; Dogs; Epilepsy; Female; Liver; Phenobarbital; Potassium Compounds

Topics: Algorithms; Animals; Bromides; Dog Diseases; Dogs; Drug Administration Schedule; Epilepsy; Phenobarbital; Potassium Compounds

In therapy lasting between 8 and 79 (means = 31) months 22 epileptic dogs had been unsuccessfully treated with phenobarbital and/or primidone. Both drugs had been administered in their maximum dosages. In an add-on therapy, these dogs were given potassium bromide at a rate of 17 to 58 mg/kg daily for a period of 7 to 61 (means = 21) months. We could quantitatively evaluate the seizure data from 19 of the dogs: four became free of seizures; seven showed a greater than 50% reduction in seizure frequency; in two dogs, the seizures were reduced by greater than 50% but the number of seizure-days by less than 50%; in the remaining six dogs the therapy was unsuccessful. We achieved the best therapeutic results in animals that suffered only grand mal seizures. Grand mal in addition to other types of seizures and tonic seizures were affected to a lesser extent if at all. At the beginning of the therapy we saw temporary side effects--weakness in the hind limbs and sedation; these were temporary and dependent on the dosage. Serum concentrations differed even with the same dosage among individual dogs. The therapeutic range of bromide serum concentration was from 0.7 to 2.0 mg/ml. Most of the animals tolerated concentrations up to 1.5 mg/ml quite well. To begin an add-on therapy with potassium bromide we would recommend a daily dose of 30 to 40 mg/kg. During treatment, the dose should be determined for each individual dog.

Topics: Animals; Bromides; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Drug Resistance; Epilepsy; Epilepsy, Tonic-Clonic; Female; Male; Phenobarbital; Potassium; Potassium Compounds; Primidone

Thirty-six children with epilepsy resistant to conventional treatment were treated with bromides in addition to the current therapy. Six out of 19 cases with prevailingly or exclusively generalized tonic-clonic seizures became seizure-free and in 9 cases a reduction in seizure frequency of more than 50% was achieved. Freedom from seizures could not be obtained in 13 cases, who had frequent minor seizures in addition to generalized tonic-clonic seizures. In some, minor seizures were even activated. Tonic and focal seizures showed no response. Side effects were observed in one-third of the cases (acne, loss of appetite, loss of weight, fatigue) but in no case they did become intolerable. Fifty to 80 mg potassium bromide per kg body weight seems to be an effective daily dose range. There is a preferential indication of bromides for patients suffering from early onset epilepsy with generalized tonic-clonic seizures and/or alternating hemi-grand mal, for whom other treatment is ineffective. This disorder is characterized by a high familial incidence of epileptic seizures, onset between 6 months and 3 years of age, normal development until the onset of seizures, generalized tonic-clonic seizures and often alternating hemi-grand mal, seizure precipitation by fever, and occasional combination with or transition to myoclonic-astatic and/or myoclonic seizures. EEG is often normal or shows slight slowing in the initial phase; later it shows theta rhythms and generalized spikes and waves. Especially, if the onset is during the first year of life, the course of the epilepsy is often unfavourable.

Topics: Adolescent; Adult; Bromides; Child; Child, Preschool; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Male; Potassium; Potassium Compounds

Topics: Adolescent; Adult; Anticonvulsants; Bromides; Child; Child, Preschool; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Epilepsy; Epilepsy, Tonic-Clonic; Evoked Potentials; Female; Humans; Male; Potassium; Potassium Compounds