CPD ACCREDITED ARTICLE
• Hyperlipidaemia and pancreatitis 53 % of epileptic dogs had serum fasting serum triglyceride levels above the reference range and a significant relationship was shown with BCS , but not with PB dose or serum concentration , increased canine specific lipase or seizure activity score . Increased polyphagia and scavenging has been put forward as a risk factor for pancreatitis in dogs receiving PB . Serum TG > 11.3 can directly affect serum PB readings depending on test methodology
• Thyroid Function Short-term ( 3 weeks ) administration of PB will not affect TT4 , fT4 or TSH serum concentrations . The long-term use of PB can decrease TT4 and fT4 into the range seen with hypothyroid dogs , while cTSH generally remains unchanged . This decline starts at about 3 weeks and continues all the way through to 6 months after which it seems to stabilise .
... Consensus recommendation continued
Phenobarbitone shows dose related transient effects such as sedation and these resolve within a few weeks . Chronic adverse effects are polyphagia and polydipsia . The most common serum change is increased ALP which can occur from 2 weeks after treatment inititation . A less common life-threatening complication is drug induced hepatotoxicity ( rapid increase ALT and bile acids ), which is correlated with the higher serum levels (> 35ug / ml ). Important idiosyncratic reaction is immune mediated bone marrow disorders and possible toxic epidermal necrolysis ( TEN ).
Bromide is generally well tolerated by the dog - common transient side effects being sedation , ataxia polydipsia and polyphagia . Bromide can cause contact irritation to the stomach mucousa causing vomiting . This is minimised by splitting the doses . Bromism may occur at levels > 3000mg / L and is more likely in animals with renal impairment .
( T0 ) TT4 = 24.5nmol / L , ( T3w ) TT4 = 19nmol / L , ( T6months ) TT4 = 17.6nmol / L
TT3 concentrations are not affected by PB - which would explain the normal cTSH as T3 is the major regulator of TSH secretion .
Epilepsy per se is not a cause of euthyroid sick syndrome however recent seizure activity ( within 24hrs prior to blood collection ) caused a significant decrease in T4 .
Clinical signs of hypothyroidism and some of the side effects of PB are similar : lethargy , weight gain , hypercholesterolaemia and lipidaemia . Interpret with great caution any low TT4 result you get when testing a patient on PB treatment .
The cTSH is likely to be normal with PB induced euthyroid sick syndrome - so requesting a cTSH may assist in making a diagnosis , as 60 % of hypothyroid dogs have an elevated cTSH . However if you do decide to supplement thyroxine - it will induce drug metabolising enzymes and may cause increased PB metabolism and reduced steady state concentrations requiring dosage increases .
Thyroid function will normalise at 4 weeks after cessation of PB treatment .
• Adrenal function : Phenobarbitone has no significant effect on ACTH stim test or LDDST test .
POTASSIUM BROMIDE Potassium ( PB ) bromide is an attractive alternative to pheno-babritone as a sole therapy as it is freely available , is not expensive , has a very long elimination half-life and has less side effects than PB .
The t ½ of bromide is 15 – 46 days . The dose is 30mg / kg / day with food ( a liquid formulation causes less vomiting ).
Levetiracetum side effects are predictable and dose dependent . They include sedation , ataxia , restlessness and vomiting
Zonisamide causes sedation ataxia , inappetance and vomiting - in some dogs these were transient and in other dogs dosage reductions were required . Suspected life-threatening idiosyncratic events include acute toxic hepatopathy . Zonisamide may affect thyroid testing .
When should a second AED be started ? Risk factors associated with poorer seizure control include male dogs and prior clustering seizure activity . Strict criteria for add-on therapy are lacking in veterinary science .
Phenobarbitone has important drug-drug interactions with other drugs metabolised by the liver due to its microsomal enzyme induction effect and this can influence the concentrations of other drugs used .
Concomitant bromide and PB therapy has been reported to decrease the number of seizure events . This allows for a decrease in the dose of PB , which also reduces the long term risk of hepatotoxicity .
Imepitoin , when added to PB therapy in a prospective trial of 17 dogs showed a decrease in seizure frequency in most dogs .
Levetiracetum is classically used as a third add-on drug to phenobarbitone and bromide . TID treatment is required . In most reports approximately 50 % of animals responded (> 50 % decrease seizure frequency ) however in one trial a relapse was seen after 4-8 month of continuing treatment .
Zonisamide as an add-on is effective in about 80 % of cases in the initial 4 months but is did appear that there may also be a delayed relapse during long term follow up in some cases .
Issue 06 | FEBRUARY 2017 | 9