OWNER EXPECTATIONS AND MONITORING RESPONSE

Expectations

It is important to manage the client's expectations. If they start treatment with unrealistic hopes of what can be achieved they will be more likely to become disillusioned and treatment failure will result.

 

Instructions to owners

The owner must fully understand the implications of the disease before starting treatment. It is important that the owner knows what to expect in terms of response to treatment and is aware of the possibility of status epilepticus and how to manage it. Commitments from the owner include keeping a seizure diary and being willing to schedule appointments at least once a year (with further contact between times as necessary)

 

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Important messages for client

Dogs with primary epilepsy are normal animals with lower seizure threshold.

The aim of anticonvulsant treatment is not to cure epilepsy but to “control” it.

Side-effects of anticonvulsant treatments are occasionally worse than the seizures themselves.

Mild side-effects are common when first starting treatment with anticonvulsant drug.

Therapeutic effects and side-effects are related to serum level and not oral dosage of the anti-epileptic drug.

Oral anticonvulsant drugs may take a long time to be effective, so seizure control may not be immediate.

Client must keep accurate record of witnessed or suspected seizures.

Client must be willing to bring their dog or cat in for periodic examination.

Client should seek immediate veterinary care for any seizure lasting longer than 10 minutes or for clusters of seizures without recovery between.

Client should not alter the treatment without veterinary advice.

Skipping doses or stopping drugs abruptly can precipitate seizures.

Serum Monitoring Scheme

Phenobarbital

Therapeutic and toxic effects of phenobarbital are related to serum concentrations and not the quantity of drug administered orally. Therapeutic monitoring of serum phenobarbital concentration can be helpful in determining the optimal dose.

 

Monitoring should be performed:

When steady state blood levels are reached after starting treatment or after changing oral dosage (12 to 15 days in dogs). This provides a baseline to guide further changes in doses according to clinical circumstances.

If seizure frequency increases.

Every 3 to 6 months to verify that blood concentrations are maintained in the therapeutic range.

If drug-related side-effects are suspected.

If drugs are added that might interfere with phenobarbital's pharmacokinetics (corticosteroids, cimetidine, chloramphenicol).

 

Recommended therapeutic range in dogs is 20 to 35 ug/ml (65-194 µmol/l). Most dogs will respond (reduction in frequency, intensity and severity of the seizures with minimal side-effects) when the serum level of phenobarbital is within this range. However, some dogs might need to be in the upper limit of this range while others might need to be below the lower limit.

 

It has been recommended that blood samples for measuring serum concentrations should be taken at the time of trough serum phenobarbital concentrations (up to 2 hours before the next dose is due). A study by Levisitski and Trepannier (2000) showed that there was no therapeutically relevant change in serum concentrations during the 12 hour period between phenobarbital doses in 33 epileptic dogs. Analysis of data from over 1400 dogs in the Vetoquinol serum monitoring scheme has confirmed that at oral doses <10mg/kg there was no significant difference between trough and non-trough serum phenobarbital levels on dogs on continuous treatment. At oral doses >10mg/kg a significant difference was seen and in these dogs it is important to be consistent in the timing of blood sampling relative to dose times so that sequential samples can be compared.

 

This therapeutic range is only an indication of changes required in the oral dosage.

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 relative to dose times so that sequential samples can be compared.

Bromide

Therapeutic and toxic effects of bromide are related to serum concentrations and not the quantity of drug administered orally. Therapeutic monitoring of serum bromide concentration can be helpful in determining the optimal dose.

 

Monitoring should be performed:

When steady state blood levels are reached after starting treatment or after changing oral dosage (3 to 6 months in dogs). This provides a baseline to guide further changes in doses according to clinical circumstances.

If seizure frequency increases.

Every 6 to 12 months to verify that blood concentrations are maintained in the therapeutic range.

If drug-related side effects are suspected.

 

Recommended oral dosage in dogs is 30 mg/kg once daily. Therapeutic serum concentrations are 880 to 3000 mg/ml as a solitary agent and 810 to 2400 mg/ml in combination with phenobarbital.

 

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References:

Monteiro R, Anderson TJ, Innocent G, Evans NP, Penderis J (2009) Variations in serum concentration of phenobarbitone in dogs receiving regular twice daily doses in relation to the times of administration. Vet Rec 165, 556-559. - PubMed -

 

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