Page 798 - Clinical Small Animal Internal Medicine

766 Section 8 Neurologic Disease

Drug tolerance over time, known as the “honeymoon dependence, compared to the full agonist AED drugs like
VetBooks.ir effect,” can occur. However, wide individual patient phenobarbital and diazepam. Imepitoin was recently
approved for use in canine epilepsy in Europe and is
drug metabolism may be associated with this phenom-
enon. As such, this author advocates incremental esca-
the United States.
lation by 10 mg/kg/dose per week when seizures persist undergoing clinical investigation for FDA approval in
to a maximal tolerated dose. No upper limit dosage
exists due to a high therapeutic index (safety) for A summary of AED therapy is shown in Table 70.1.
this drug. A parenteral formulation is available for
intravenous loading at 40–60 mg/kg over 15–30
minutes in a 1:1 diluted saline solution. Movement Disorders

Third‐Generation AEDs Cats and dogs can develop a variety of unusual movement
Lacosamide disorders that bewilder even the most seasoned clinicians
This is a functionalized amino acid proven to decrease due to the difficulty in determining their neuroanatomic
neuronal discharge frequency and synaptic excitability. origin and etiology. Movement disorders include a wide
The postulated mechanisms of action include selective range of neurologic disturbances, characterized by either
slow inactivation of sodium channels and novel binding excess (hyperkinesia) or reduced (bradykinesia) move-
to collapsin response mediator protein‐2. In humans, the ments. These abnormal involuntary movements (AIMs)
drug is well absorbed, has minimal first‐pass effect with refer to a number of muscle jerks, twitches, postures, and
predominant renal excretion, low protein binding, oscillations that have been classified in human neurology
favorable drug–drug interactions with other AEDs, and with official terms such as tic, chorea, tremor, dystonia,
is well tolerated. Clinical trials in humans have demon- and myoclonus. Uncontrolled muscle contractions may be
strated a comparable decrease in seizure frequency with of muscle or neuronal origin.
that of levetiracetam and zonisamide at a dose of 100–
200 mg orally q12h. A parenteral formulation is available
for intravenous loading. The author has used lacosamide History
to successfully treat refractory idiopathic epilepsy in The saying “A picture is worth a thousand words” is made
dogs at a dose range of 5–10 mg/kg q12h. for movement disorders. The ability to visualize the
characteristics of AIMs should be supplemented with a
Rufinamide detailed history to characterize the nature of the move-
This novel drug is structurally unrelated to any other ment disorder. Information regarding anatomic distribu-
AED. Its main mechanism of action is related to prolon- tion, rhythmicity, amplitude, frequency, speed of onset
gation of the inactive state of the sodium channel, thus and offset of the movement, relationship to posture and
preventing neuronal depolarization. In humans, the drug activity, situations that alleviate or exacerbate the move-
is absorbed slowly and has low bioavailability. Renal ment, presence or absence during sleep, and affected
excretion is high and no induction of the hepatic P450 littermates are all essential to help determine the neuro-
system has been found, although other hepatically anatomic localization and potential etiology. If the
metabolized drugs decrease the serum concentration. Of movement disorder is not present at the time of the
a total of nine double‐blinded studies in humans, five examination, owners should be encouraged to video
revealed a positive effect of rufinamide to treat refrac- the events for future review. Many times, the initial few
tory partial seizures but not generalized seizures. In bea- minutes of observation will solidify the clinical perspec-
gle dogs, the mean terminal half‐life ranged between five tive, allowing an accurate diagnostic and therapeutic
and 14 hours. In people, dose‐dependent adverse effects course of action to proceed.
include sedation, fatigue, and dizziness. Initial dosing in
the dog is 20 mg/kg q12h. Serum concentration can be Etiology and Pathophysiology
monitored to achieve a therapeutic range of 10–25 μg/
mL. A parenteral formulation is not currently available. The process of initiation and completion of voluntary
movement is a complex one that relies on coordination
Imepitoin of serial communications between multiple components
This drug is the first AED that acts as a low‐affinity of the central and peripheral nervous system. Failure of
partial agonist at the GABA‐A benzodiazepine receptor any of these components to complete their assigned
site. The advantage is that imepitoin is associated with tasks can result in either loss of the desired movement or
fewer adverse effects of sedation and ataxia, and is less excessive, abnormal movements. A summary of move-
likely to develop functional drug tolerance or physical ment disorders in dogs is provided in Box 70.2.