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Controlling primary epilepsy (Proceedings)

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Oct 01, 2008

1. Actions of anticonvulsant drugs: Prevent spread of the seizure focus; increase (raise) the seizure threshold; decrease electrical excitement of abnormal neurons without disrupting normal function.

2. If your overall goal of anticonvulsant therapy is to eliminate all seizure activity, there is a good chance you'll fail. A more reasonable goal: Reduce frequency, severity, and duration of seizures without intolerable or life-threatening adverse affects to the animal.c

3. Approximately 20-30% of epileptic dogs will not be controlled adequately using currently available antiepileptic drugs. Larger breeds of dogs are more difficult to control.

4. Treatment with a single drug should be attempted initially to simplify monitoring and management of adverse side effects.

5. Phenobarbital and bromide are usually the first anticonvulsant choices in the dog. Phenobarbital is first choice in the cat.

6. Successful therapy requires a basic knowledge of the pharmacology and deleterious effects of the medications as well as the ability to "fine tune" doses. For some owners, the side effects of anticonvulsants are not "worth" the seizure control.

7. When to start anticonvulsants: A. After 2nd or 3rd seizure in a dog with suspected primary epilepsy unless seizures are many months apart. B. During status epilepticus cases. C. After 2nd or 3rd seizure in same day unless there is a metabolic reason (hypoglycemia, hepatic encephalopathy, etc) or toxic cause of the seizures.

8. Before starting anticonvulsants, consider the owner's compliance and ability to medicate the pet, the owner's expectations, the pet's environment and use, the cost of the drug.

Dogs: Which Is Best To Start With: Phenobarbital(Pb) Or Bromide (Br)?

One study in 2002 (and the experiences of most neurologists) indicates that both PB and BR are reasonable first choices for control of epilepsy in dogs. In the 2002 study, Phenobarbital eradicated seizure activity in a greater percentage (85%) of patients compared to BR (65%). However, successful control (at least 50% reduction in seizure number) did not differ between the two drugs at 6 months. Both drugs caused abnormal behaviors (ex: weight increased by 10% in both groups). Changes in clinical pathology were limited to increased (but within normal) serum alkaline phosphatase and decreased (but within normal) serum albumin at 6 months for PB compared to baseline and compared to BR at 6 months. The incidence of obtundation and vomiting were greater in BR patients compared to PB patients at 6 months.

Mechanism

Phenobarbital (PB) potentiates the actions of GABA, an inhibitory neurotransmitter in the CNS. GABA stabilizes postsynaptic neurons by increasing chloride conductance into the cell. The increased intraneuronal chloride stabilizes the cell membrane. Dogs that have low CSF concentrations of GABA prior to therapy will have a reduced response to PB therapy. Barbiturates also decrease calcium influx into nerve cells, which decreases release of neurotransmitters.

Metabolism

Liver. Induces p450 enzymes, so may result in increased metabolism of concurrently administered drugs (digoxin, glucocorticoids, clorazepate, griesofulvin). Microsomal inhibiting drugs (chloramphenicol and tetracyclines) may inhibit phenobarbital metabolism so watch for signs of toxicity). Phenobarbital often results in increased ALP, GGT in dogs; less likely to increase ALT, AST. Increased liver enzymes do not equal hepatotoxicity! If there are questions as to liver function, perform pre- and post-prandial bile acids.

Pharmacokinetics

Half-life is about 30-70 hours for dog and 34-83 hours for cat. Steady state is reached in 10-14 days. Recommended therapeutic serum level in μg/ml: 15-40 dogs and 10-30 cats.