Alternative anticonvulsant drugs for dogs with seizure disorders - Veterinary Medicine
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Alternative anticonvulsant drugs for dogs with seizure disorders
People with seizure disorders have many drug options, but are there safe and effective alternatives to phenobarbital and bromide in dogs? These clinicians share their knowledge of the most promising new drugs.


VETERINARY MEDICINE


The limited published material on felbamate's efficacy mirrors our clinical experience. In one report of refractory epileptic dogs, 12 of 16 patients had reduced seizure frequency after felbamate therapy was initiated.16 In another report of six dogs with suspected focal seizure activity, all six dogs experienced a substantial reduction in seizure frequency when felbamate was used as a sole anticonvulsant drug; two of these dogs became seizure-free.19

We have used felbamate extensively to treat dogs with seizure disorders. In our experience, felbamate is effective both as an add-on therapy and as a sole anticonvulsant agent in patients with focal and generalized seizures. Because felbamate does not have a sedative effect, we have found it particularly useful as a monotherapy in dogs exhibiting obtunded mental status from their underlying neurologic disease (e.g. brain tumor, cerebral infarct). We have found side effects from felbamate to be infrequent. However, because of the potential for hepatotoxicity, serum chemistry profiles should be preformed every six months in dogs receiving felbamate, especially if they are receiving phenobarbital concurrently. It would also be prudent to perform complete blood counts every few months, in the unlikely event that a blood dyscrasia develops.

Gabapentin

Gabapentin is a structural analogue of GABA. Gabapentin appears to exert its antiseizure effects by enhancing the release and action of GABA in the brain and inhibiting neuronal sodium channels.1,2,8,10,17,18 Gabapentin is well-absorbed in both dogs and people, with peak serum concentrations occurring within one to three hours after administration. In people, absorption is somewhat dose-dependent, relying on a saturable amino acid transport mechanism in the gastrointestinal tract. This saturable transport process has been theorized as the reason anticonvulsant effects may last longer than expected based on the serum half-life of the drug.2,17

In people, virtually all of the drug is excreted unchanged in the urine (i.e. no hepatic metabolism). In dogs, however, 30% to 40% of the oral dose undergoes hepatic metabolism to N-methyl-gabapentin.1,2,8,10,20,21 Even though gabapentin undergoes some hepatic metabolism, there is no appreciable induction of hepatic microsomal enzymes in dogs. Gabapentin's half-life in dogs is three or four hours. The recommended dosage in dogs is 25 to 60 mg/kg divided every six to eight hours.1,2,10,20,21 We recommend an initial dosage of 10 mg/kg given every eight hours. The suspected serum therapeutic range in dogs is 4 to 16 mg/L.18 As with felbamate, serum gabapentin concentrations are rarely obtained in dogs.

Although long-term toxicity trials in dogs have not been reported, gabapentin seems to be well-tolerated, usually with no sedation or other side effects. There are no clinical reports on the efficacy of gabapentin in dogs with seizure disorders. In our experience, gabapentin is only occasionally useful in dogs. In people, gabapentin appears to be much more effective in treating focal rather than generalized seizure disorders.18 Because of its short half-life in dogs, gabapentin should be administered at least every eight hours, and possibly every six hours, to maintain serum gabapentin concentrations within the therapeutic range. The potential need for giving the drug every six hours can make it difficult for some pet owners to reliably administer gabapentin.

Levetiracetam

Levetiracetam is a new anticonvulsant drug for treating focal and generalized seizure disorders in people and has been studied in several experimental animal models.1,17,18,22-26 The mechanism of action for levetiracetam's anticonvulsant effects is unknown. Unlike other anticonvulsant drugs, levetiracetam does not appear to directly affect common neurotransmitter pathways (e.g. GABA, NMDA) or ion channels (e.g. sodium, T-type calcium).17,22-24 There is some evidence that levetiracetam may inhibit high-voltage-activated neuronal calcium currents. Levetiracetam may also act by interfering with negative allosteric modulators of inhibitory GABA and glycine pathways in the brain.23,24


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Source: VETERINARY MEDICINE,
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