CPD ACCREDITED ARTICLE
Bromide is water soluble and absorbed along entire GI . Prandial state doesn ’ t affect absorption - if given with food you may get less gastric irritation .
Serum bromide levels should be between 1 – 3 mg / ml as a sole treatment .
Because of the long t 1 / 2 it will take months to attain therapeutic levels unless a loading dose is given . A loading protocol tested was 600mg / kg bromide together with the 30mg / kg / day maintenance dose given over 48 hrs . The full dose was divided into 10 smaller doses to avoid vomiting . Using this protocol 84.2 % patients were in therapeutic range of 1 – 3mg / mL after 48 hrs , 13 % were not ( 0.74 – 0.95mg / L ).
The drug is renally excreted . Bromide competes with chloride for reabsorption by the kidneys . Increase in dietary salt from 0.2 % to 1.3 % decreased the elimination half-life from 69 days to 24 days - so diet changes may profoundly affect serum levels and increase the risk of seizures .
Common side effects are polyuria , polydipsia and polyphagia , mild transient sedation as well as irritability and restlessness . Depression , ataxia , behavioural changes , mydriasis and stupor occur with more severe bromism . Adverse neurological effects are reversible and resolve within several days if bromide dose is reduced and within hours when patients are treated with IV saline due to increased renal excretion of the bromide .
Effective and toxic levels overlap and individual monitoring , using clinical signs , is probably the most practical .
Pancreatitis has been suggested as a side effect of KBr and has been associated with dogs with epilepsy . This association was made using amylase and lipse as indicators of pancreatitis – which are not really specific . When cPLi was used no risk was detected . Some reports indicate that dogs show increased pruritis . KBR doesn ’ t affect serum thyroxine levels ( TT4 ), fT4or cTSH .
Bromide in cats causes coughing and dyspnoea and an influx of eosinophils into the bronchi - allergic bronchial disease – causing a severe bronchial lung pattern on radiographs .
Primidone Is rapidly metabolised to PB - which is responsible for more than 85 % of its antiepileptic activity . It is however less effective or as effective then PB alone and is less well tolerated in dogs . Not recommended
Imepitoin Imepitoin was originally developed for the treatment of anxiety and epilepsy in people . Development of the drug for humans was terminated due to an effect smoking had on the drug , thus development continued only in the canine field . Imepitoin potentiates GABA-nergic inhibition . The drug is administered BID in incremental doses of 10 , 20 or 30mg / kg .
Levetiracetam Levetiracetam ( LEV ) has been used in pharmaco-resistant dogs and resulted in a decreased seizure frequency in 54 % of patients . The drug has limited hepatic metabolism and the plasma t ½ in dogs is 3.6 ± 0.8 hrs , which will require TID administration . The drug is well tolerated in dogs and has no side effects apart from mild sedation .
A recent study sought to evaluate the long-term effects of this drug and it was administered at 10mg / kg tid for 2 months and in patients which showed a poor response (< 50 % decrease in seizure activity ) the dose was increased to 20mg / kg TID . Eight of 14 dogs responded to the initial dose and a further 6 patients to the higher dose . However most of the dogs experienced an increase in seizure frequency again ( relapse ) about 4-8 months after treatment was initiated .
The pharmacokinetics of LEV are significantly altered by the concurrent administration of PB , this despite hepatic metabolism playing such a small role : in dogs 89 % is excreted by the kidneys and of this approximately 50 % is unchanged . There is no canine recommended range for levetiracetum - the human reference range for plasma concentrations of LEV is 5 – 40μg / ml . If using this drug as an add-on - monitoring of serum drug levels is recommended . The mean plasma concentrations of LEV ( at a mean dose of 24mg / kg tid ) in the PB treated group was 5.52μg / ml , in the PB – KBR group was 3.06μg / ml and in the KBR group was 33.5μg / ml . However there was no difference in the reported seizure frequency between the 3 groups - although comparisons pre and post treatment in individual animals were not made in this study .
Zonisamide Has shown efficacy ( 60 % showed > 50 % decrease in seizures ) as a monotherapy in a single trial of 10 dogs followed for 12 – 36 months using it BID at 5-15mg / kg to attain serum levels of 10 – 40ug / ml
Zonisamide has a t ½ of about 15 hrs in dogs . Dosage is 10mg / kg po BID as an add-on therapy . The dosages of the previous anti-epileptics were gradually reduced in individual patients ( n = 7 ) if the patients usual seizure interval was exceeded . There was a significant decrease in seizure episodes in the 11 dogs evaluated . Eight of 10 dogs responded with a reduction of 82 % ( 58 – 100 %), Side effects reported were ataxia and sedation . These resolved in some patients when the PB was removed .
SELECTED REFERENCES ( REMAINDER ONLINE - WWW . VET360 . VETLINK . CO . ZA )
1 . Levitski RE et al . 2000 Effect of timing of blood collection on serum phenobarbital concentrations in dogs with epilepsy . Journal of the American Veterinary Medical Association . ( 217 ) p : 200 – 204
2 . Podell M , Volk HA et al . 2016 . 2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs . Journal of Veterinary Internal Medicine ( 30 ) p : 477 -490
3 . Tipold A , Keefe TJ et al 2014 Clinical Efficacy and safety of Imepitoin in comparison with Phenobarbital for the control of Idiopathic Epilepsy in Dogs . Veterinary Pharmacology and Therapeutics ( 38 ) p : 160 - 168 vet360
Issue 06 | FEBRUARY 2017 | 10