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  • Scheme findings
    Overall 43 of the dogs that were serum tested were categorised as being controlled routine with the remaining dogs almost equally divided between the other categories The category other included a lot of dogs that had just commenced phenobarbital therapy Frequency of Seizures in controlled group Expressed as a percentage of forms that had a reply for this question The group of dogs classed as being controlled were evenly divided into each seizure frequency category At either end of the scale 15 of dogs had a seizure episode every 0 2 weeks while 32 experienced a seizure frequency of 3 months or more This illustrates the wide variations in opinion as to what constitutes good control of seizures Dose of Epiphen in mg kg for controlled dogs Expressed as a percentage of forms that had a reply for this question It can be seen from the graph that more than half 50 9 of dogs reported as having their seizures controlled are receiving between 2 5 5 0 mg kg phenobarbital although more than one third are receiving a larger dose 20 4 5 0 7 5mg kg 8 8 7 5 10 mg kg and 10 2 over 10mg kg A small group of dogs with controlled seizures 9 7 are receiving 0 2 5 mg kg phenobarbital Effects of dose on serum concentrations In dogs receiving oral doses of phenobarbital 10mg kg there was a significant difference between trough up to 2 hours before dose due and non trough serum phenobarbital concentrations This effect was not significant in dogs receiving doses 10mg kg This finding means that trough blood samples are not essential for dogs receiving lower doses of phenobarbital In dogs receiving doses 10mg kg it is important to be consistent in the timing of blood sampling

    Original URL path: http://www.canineepilepsy.co.uk/scheme-findings.html (2016-02-08)
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  • Phenobarbital
    reach steady state concentration of phenobarbital in dogs Phenobarbital is primarily metabolised in the liver and causes induction of liver enzymes Indications Drug of first choice in management of canine epilepsy Dose In dogs phenobarbital can be started at 3 mg kg twice daily orally Oral doses are adjusted based on serum levels and seizure frequency Recommended therapeutic range in dogs is 20 to 35 ug ml Side effects Common side effects include polyuria polydipsia polyphagia transient sedation or hyperexcitability and ataxia These are common one to two weeks after the onset of the treatment or after increasing the oral dosage but usually resolve as tolerance develops Polyuria polyphagia and polydipsia are the most common long term side effects Other side effects include haematological abnormalities such as neutropenia anaemia and thrombocytopenia Hepatotoxicity is rare mostly seen in dogs on chronic treatment with phenobarbital serum level above 35 mg L and is characterised by sedation ataxia anorexia icterus ascites or coagulopathy with increased pre and post prandial serum bile acids low albumin increased ALT ALP bilirubin An increase in liver enzyme concentration is to be expected in all animals receiving phenobarbital and so liver function tests are required to monitor the effects on the liver Hepatotoxicity may be reversible if detected early and phenobarbital withdrawn There is an increased risk of pancreatitis in dogs receiving both bromide and phenobarbital Phenobarbital treatment does not affect adrenal function tests ACTH stimulation test and low dose dexamethasone test despite acceleration in dexamethasone metabolism Phenobarbital treatment significantly decreases total T4 and free T4 concentration TSH only shows a compensatory increase while total T3 has minimal fluctuation and cholesterol increases toward the upper limits of the normal range DOWNLOAD Epiphen tablets datasheet DOWNLOAD Epiphen solution datasheet DOWNLOAD Fact sheet on phenobarbital DOWNLOAD Guide to canine idiopathic

    Original URL path: http://www.canineepilepsy.co.uk/phenobarbital.html (2016-02-08)
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  • Bromide
    Therapeutic serum concentrations are 880 to 3000 mg l as a solitary agent and 810 to 2400 mg l in combination with phenobarbital If adequate serum concentrations are needed rapidly a loading dose of bromide can be used An oral dose of 120 to 150 mg kg for 5 days should achieve a serum concentration of 1 1 5 mg ml For a more rapid effect than that obtained with oral maintenance dosing regimes a per rectum loading protocol has been devised Intrarectal administration may be preferred in the patient that is heavily sedated from prior diazepam and phenobarbital administration The side effects seen with the use of this regime may be transient diarrhoea and sedation The maintenance dose should achieve steady state concentrations so check serum levels at 1 week and 1 month post loading These concentrations should be identical Steady state concentrations reached at about 6 8 weeks if no loading dose administered and then single trough samples are suitable for monitoring Therapeutic range of 1 3 5 mg ml should be tailored in individual patients based on tolerance and effect Once bromide concentrations are stable at 1 5mg ml phenobarbital dose may be reduced in 25 increments if required particularly if sedation is a problem In rare circumstances may be used as sole agent in which case target concentrations are higher 2 2 5 mg ml Side effects Tend to be dose dependent and include polyuria polydipsia polyphagia transient sedation or ataxia during the first 2 to 3 weeks before tolerance develops Hyperactivity and pruritus may be seen occasionally Overdosage may be associated with ataxia depression tremors neuropathies stupor or coma bromism sodium chloride IV or orally accompanied by furosemide may be considered Bromide is a gastric irritant and may cause vomiting this may be minimised by

    Original URL path: http://www.canineepilepsy.co.uk/bromide.html (2016-02-08)
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  • Diazepam
    is the drug most commonly used in veterinary medicine for the initial treatment of SE When administered intravenously transient high serum and brain concentrations of diazepam are achieved with 1 minute With its relatively brief duration of action however diazepam is not a definitive therapy for SE Lorazepam has a longer duration of protection as brain concentrations are maintained for longer Because SE may end spontaneously IV diazepam should not be administered to a patient presenting in a post ictal state unless there is another seizure Dose Recommended dose is 0 5 to 1 0 mg kg diazepam IV up to a maximum dose of 20 mg in dogs This dose can be repeated to effect or twice within two hours Constant rate intravenous infusions of diazepam have been advocated in human and veterinary patients The recommended dose is 2 5 mg hr in 5 dextrose in water This takes 15 20 minutes to penetrate the CNS but has a prolonged effect Continuous use in prolonged seizures should be avoided as a diminished response is seen with repeated administration If the diazepam does not control the seizures the use of phenobarbital 5 10 mg kg IV should be considered Intravenous administration of diazepam may not be possible in some patients It can be administered intramuscularly IM although absorption is not predictable Rectal administration of diazepam may be considered initially at a dose of 0 5 to 2 0 mg kg body weight depending upon whether the animal was being treated with phenobarbital before the onset of SE It may be necessary to use the higher dose in dogs receiving long term phenobarbital therapy In previously untreated dogs peak plasma concentrations of diazepam are seen 14 minutes after a per rectum dose of 1 mg kg Side effects Adverse effects of

    Original URL path: http://www.canineepilepsy.co.uk/diazepam.html (2016-02-08)
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  • Zonisamide
    of 5 mg kg BID can be used in dogs not concurrently receiving drugs that induce hepatic microsomal enzymes Trough serum zonisamide concentration should be checked after around 1 week of zonisamide treatment aiming for a serum concentration of 10 40 ug ml Side effects Zonisamide appears to be safe few side effects are reported in dogs although mild ataxia and sedation may occur when treatment is started and vomiting and loss of appetite have been reported in some dogs Dewey and others 2004 Has caused kidney stones in some people At a dose of 75 mg kg bodyweight four times the recommended dose slight changes in blood count and an increase of liver weight were observed in one study Walker and others 1988 References Boothe D M Pers J Dewekiny C 2005 Clinical pharmacokinetics and safety of the anticonvulsant zonisamide in healthy dogs following single and multiple dosing In Proceedings of the 23rd ACVIM forum Baltimore USA pp 858 Budsberg S C 2004 Zonisamide therapy for refractory idiopathic epilepsy in dogs Journal of the AmericanAnimalHospital Association 40 285 291 PubMed Dewey C W Guiliano R Boothe D M Berg J M Kortz G D Joseph R J Budsberg S C 2004 Zonisamide therapy for refractory idiopathic epilepsy in dogs Journal of the AmericanAnimalHospital Association 40 285 291 PubMed Hamada K Song H K Ishida S Yagi K Seino M 2001 Contrasting effects of zonisamide and acetazolamide on amygdaloid kindling rats Epilepsia 42 1379 1386 PubMed Juergens U 1987 Simultaneous determination of zonisamide and nine other anti epileptic drugs and metabolites in serum Journal of Chromatography 385 233 240 PubMed Kaneko S Okada M Hirano T 1993 Carbamazepine and zonisamide increase extracellular dopamine and serotonin levels in vivo and carbamazepine does not antagonize adenosine effect in vitro mechanisms of blockade

    Original URL path: http://www.canineepilepsy.co.uk/zonisamide.html (2016-02-08)
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  • Additional drugs
    This study suggests that pregabalin may be a useful adjunctive therapy in the management of refractory epilepsy in dogs particularly in the presence of cluster seizures However as with many human drugs cost may be a significant barrier to use of this drug in dogs A study by clinicians at the Animal Health Trust in Newmarket looked at the efficacy of gabapentin as an adjunctive therapy for the management of refractory idiopathic epilepsy in dogs Five of 11 dogs with refractory idiopathic epilepsy showed a significant reduction in seizure frequency when treated with gabapentin However many dogs still had cluster seizure activity on multiple days Gabapentin was well tolerated five dogs exhibited mild side effects ataxia and sedation This small study indicates that gabapentin may reduce seizure frequency in some dogs with refractory idiopathic epilepsy A larger study is warranted to further evaluate the potential benefits of gabapentin in epileptic dogs Like many human drugs gabapentin will be an expensive treatment for dogs The use of felbamate has been documented in 6 dogs which all showed an improved seizure frequency after a median duration of therapy of 9 months potential side effects in dogs include haematological abnormalities keratoconjunctivitis sicca and hepatotoxity as reported in man Although sedation is not seen with this drug excitability has been reported at high doses The cost of treatment with felbamate will also be high In a study using zonisamide twice daily in 12 dogs with refractory idiopathic epilepsy 58 of dogs responded favourably experiencing a mean reduction in seizures of 81 3 Five of the twelve 42 dogs actually had an increased seizure frequency and 50 of the dogs exhibited side effects which included sedation ataxia and vomiting Zonisamide is not licensed for use in the UK The Royal Veterinary College in association with the Animal Health Trust has recently run completed a clinical trial to test the efficacy of Levetiracetam the most well tolerated anti epileptic drug in man with adverse reactions equivalent to placebo In man this is a highly effective adjunctive therapy to control seizures refractory to standard treatment The results of this trial suggest that levetiracetam is also well tolerated in dogs Although the dogs in the trial were refractory to phenobarbital and bromide treatment levetiracetam produced a reduction in seizure frequency in around half the dogs However after around 4 8 months of treatment seizure frequency increased again in many of these dogs Phenytoin has little place in the management of canine epilepsy due its rapid metabolism in dogs A slow release formulation is now available but no trials have been published on slow release phenytoin and the presently available form should not be used with phenobarbital and has erratic gastrointestinal bioavailability It is essential that the use of any new treatment is properly documented to identify potential benefits and adverse effects The anecdotal reports of success with any treatment must be interpreted with great caution Benefit to the whole canine population can only be achieved by an evidence

    Original URL path: http://www.canineepilepsy.co.uk/additional-drugs.html (2016-02-08)
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  • Other management
    possibly showed less severe signs and in 2 there was no response The author concluded that the results were encouraging and should be tested in a larger group of patients A new canine auricular acupuncture point for the treatment for epilepsy was studied by Panzert and Chrisman in 1994 The new acupoint was used with a previously reported canine auricular acupoint van Neikerk and Eckersley 1988 for the treatment of epilepsy in five dogs This study reported testimonial evidence only but concluded that the technique is worthy of scientific investigation and controlled research is proposed Since that time the work does not appear to have continued at least follow up results are not reported Permanent acupuncture has been advocated as an adjunct to conventional therapies for the management of epilepsy in man This involves the implantation of gold beads at sites of acupuncture points under anaesthesia Some extreme claims are made for this treatment in dogs up to 60 of epileptic dogs are cured with little supportive published data In one published study from the Veterinary Hospital of the University of Pennsylvania Klide and others 1987 five epileptic dogs unresponsive to high levels of antiepileptic medication were treated at the acupuncture clinic Small gold implants were placed subcutaneously over the calvaria to provide constant stimulation at specific acupuncture points All five dogs showed a change in seizure patterns following gold implant placement Two dogs had decreases in seizure frequency with their medication continued unchanged but reverted to their previous seizure pattern approximately five months after treatment Three dogs continued to have decreased numbers of seizures and were maintained on decreased levels of anticonvulsants The data from these reports is difficult to interpret due to the lack of a comparable control population It would however seem that provided it is used as an adjunctive to conventional therapy under veterinary control acupuncture may offer a safe alternative to other unlicensed treatments Vagal nerve stimulation A novel idea in the management of human epilepsy is the use of vagal nerve stimulation VNS The vagal nerve is unique among peripheral nerves of the body in that its nuclei begin in the brainstem It is not known how VNS achieves an anti epileptic effect One theory is that the stimulation scrambles some of the synchronous discharges of the brain associated with seizure activity Periodic scrambling of the discharges may prevent the recruitment phase needed to begin a seizure VNS has not been shown to be more effective than any anticonvulsant in man its advantage lies in its lack of central nervous system side effects sedation and ataxia However it has its own transient side effects of neck pain and voice change When effective VNS permits dose reduction or elimination of anticonvulsant drugs and also seems to shorten the duration of seizures and recovery time Some human patients do well with this treatment but it is not possible to predict which will benefit Investigation of this technique in dogs has been sketchy Digital ocular compression to

    Original URL path: http://www.canineepilepsy.co.uk/other-management.html (2016-02-08)
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  • Lafora disease
    of the abnormal gene or have the disease Diagnosis In the miniature wire haired Dachshund and Basset Hound the disease causing genetic mutation has been identified however at the present time no commercial DNA blood test exists The disease may be diagnosed by identification of the Lafora bodies in a liver muscle or nerve biopsy Differential diagnosis The main differential diagnoses are other causes of seizures and idiopathic epilepsy Haematology and biochemistry should be performed to rule out reactive causes of epileptic seizures Magnetic resonance imaging is useful to identify structural brain disease which may cause acquired epilepsy Idiopathic epilepsy typically occurs in younger dogs 6 months 6 years and in most breeds myoclonus is not a feature Hematology biochemistry Urinalysis Normal Other Laboratory tests Lafora bodies may be identified in a liver muscle or nerve The liver is the most reliable biopsy site Magnetic resonance imaging Normal Treatment Anecdotally Miniature Wirehaired Dachshunds with early Lafora s disease respond to a proprietary antioxidant rich diet Hills b d Hills b d has been shown to protect nerve cells against oxidative damage however this may not be the mechanism by which it is effective for Lafora disease as the same beneficial effect is not seen if the dog is maintained on the existing diet and supplemented with anti oxidants It is possible that Hills b d is effective because it has a low glycaemic index Starchy sugary treats may aggravate the condition and should be avoided Other diets with a low glycaemic index may be effective Epilepsy should be treated symptomatically In some cases this can be difficult as some dogs do not respond to traditional drugs like phenobarbital The author typically starts with potassium bromide at 30 40mg kg once daily A serum bromide concentration should be assessed 8 16 weeks after initiating the drug it takes 4 months to achieve steady state so ideally 16 weeks aiming for a concentration of 1000mg l 15 mmol l 2000mg l 25mmol l Higher serum concentrations are acceptable if there are no adverse effects e g sedation and ataxia If this concentration has been achieved and the number of seizures is still unacceptable then phenobarbital at 3mg kg every 12 hours should be added Phenobarbitone should also be considered if there are clusters of seizures A serum phenobarbital concentration should be assessed 2 weeks after initiating the drug If the seizures are still not adequately controlled when the phenobarbital serum concentration is 25mg l 120μmol l then switching to an unlicensed anti epileptic drug should be considered The author typically chooses Levetiracetam Keppra at a dose of 10 20mg kg twice to three times daily Coincidently with starting the levetiracetam the phenobarbital is slowly withdrawn as long as the seizure frequency does not increase Anecdotally levetiracetam is more effective than phenobarbital or bromide for controlling the myoclonus jerking and one should consider using this drug as first line therapy if the myoclonus is disabling Some dogs have a problem walking in sunlight

    Original URL path: http://www.canineepilepsy.co.uk/lafora-disease.html (2016-02-08)
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