Page 795 - Clinical Small Animal Internal Medicine

70 Seizures and Movement Disorders 763

effect. From these guidelines, several commonalities and maintaining a normal lifestyle for both the patient
VetBooks.ir exist for guiding clinical practice, including confirmation and owner are all important considerations. Whilst many
drugs may provide initial improvement in seizure
of an epileptic seizure event and seizure type, obtaining a
definitive diagnosis, knowledge that recurrent seizure
With only approximately 60–80% of human and canine
activity is correlated with poorer long‐term treatment control, long‐term efficacy is dependent on many factors.
success, and the influence of treatment on the patient’s epileptic patients responding to treatment, evaluating
quality of life. Thus, the decision to treat is a reflection of the reasons for recurrent seizure activity (refractory
the treatment goals to reduce or eliminate epileptic epilepsy) is important.
events, reduce seizure severity, avoid adverse effects, and These factors can be separated into three “Ds”:
reduce seizure‐related mortality and morbidity. Disease‐related, Drug‐related or Dynamic‐related fac-
tors. Disease‐related factors include the presence of an
Initiating Treatment undiagnosed underlying brain disease, such as cortical
Overwhelming evidence exists in humans that there is dysplasia, prior trauma or an active disease process.
no benefit in starting treatment after a single unpro- Occult conditions can lead to localization‐related epi-
voked event However, the earlier AED therapy is initi- lepsy, where epileptic foci develop drug resistance due to
ated, the better the potential outcome may be for seizure architectural brain changes.
control. Drug‐related factors include an ineffective mechanism
Reasons to initiate AED therapy include the following. of action, development of tolerance and alteration of the
drug target or uptake over time. Seizure‐specific therapy
Structural epilepsy is diagnosed.
● targets a drug for a specific seizure type, and inappropri-
Status epilepticus has occurred (ictal event of five
● ate drug selection may result in poor control. The rea-
minutes or longer).
Two or more isolated seizures occur within a six‐month sons for drug tolerance or loss of effectiveness can be
● categorized as either metabolic (pharmacokinetic) or
period.
Two or more cluster seizure events (two or more sei- functional (pharmacodynamic). Metabolic tolerance is
● due to altered drug metabolism, which occurs in an
zures within a 24‐hour period) occur within a 2–3‐ unpredictable fashion. As such, a change in drug dosage
month period.
The first seizure is within one month of a traumatic event. does not result in a parallel change in serum drug level.
● During this time, autoinduction of the cytochrome P450
Severe or unusual postictal effects are present (e.g.,
● enzyme system increases drug clearance and is not dose
prolonged blindness, aggression).
dependent. Serum drug levels decline over time with the
same dose until steady‐state clearance is achieved.
Drug Selection Concomitant drug usage that either inhibits or stimu-
Selection of AED is based on a number of factors, includ- lates the P450 system also alters hepatic metabolized
ing seizure type, efficacy, and tolerability. No evidence AED levels. Functional drug tolerance, also known as
exists that any single AED provides a better outcome for pharmacoresistance, is due to reduced drug transport
adults with unprovoked epilepsy when early treatment is through the blood–brain barrier, long‐term downregula-
initiated. Monotherapy is still the recommendation for tion of the target receptor or genetic factors that alter
new‐onset epilepsy. The use of a single AED has the cellular metabolism of the drug.
advantages of no drug interactions, more predictable Dynamic‐related factors are now being discovered in
pharmacokinetic and pharmacodynamic properties, less relation to gene polymorphisms that affect AED phar-
potential for adverse effects, and less expense to the macokinetic or pharmacodynamic properties. As a
client. result, altered drug metabolism or action is no longer
Antiepileptic drugs are classified into three broad
mechanistic categories which decrease either the seizure predictable when compared with the general patient
population. In addition, a placebo effect has been dem-
onset or spread of seizures:
onstrated in epileptic dogs, indicating that nonpharma-
enhancement of inhibitory processes via facilitation of cologic therapeutic effects may play a role in canine
●
GABA action epilepsy treatment.
reduction of excitatory transmission
●
modulation of membrane cation conductance. First‐Generation AEDs
●
Phenobarbital
Success Parameters Phenobarbital (PB) has the longest history of chronic use
The treatment of epilepsy should be goal oriented and of all AEDs in veterinary medicine. It is a relatively
approached in an objective fashion. Eliminating or sig- inexpensive, well‐tolerated drug and has documented
nificantly reducing the number and severity of seizures success in preventing seizures. Phenobarbital has a high