Lect 9

• Anticonvulsants are drugs used to block seizure initiation and propagation by blocking either abnormal events in a single neuron or the synchronization of related neurons.
• The goal of therapy with anticonvulsant drugs is reduction in the firing frequency of neurons.
• Only a few of the anticonvulsant drugs available for human use have been approved for clinical use in dogs and cats.
• Some of the anticonvulsant drugs are too rapidly metabolized in dogs to be effective, even in high dosages.
• Cats metabolize drugs more slowly and poorly than dogs.
• The pharmacokinetics of Midazolam in dogs show a shorter elimination half-life of 77 min.
• Midazolam can cause changes in behavior in dogs, including irritability, depression, and aberrant demeanor.
• Cats may develop acute fatal hepatic necrosis after receiving Midazolam.
• In dogs, Midazolam is the drug of choice for the control of emergency status epilepticus and cluster seizures.
• Midazolam is more potent than diazepam and is used for status epilepticus, muscle relaxant, tranquilizer, and appetite stimulant the same way as diazepam.
• Anticonvulsant drugs act by stabilization of the neuronal membranes evoking hyperpolarization.
• Anticonvulsant drugs activate GABA-gated Cl-channels.
• Anticonvulsant drugs bind to GABA A receptor and facilitate its action (agonist).
• Anticonvulsant drugs inactivate Na+ and Ca+ conductance.
• Therapeutic uses of anticonvulsant drugs include reduction of incidence, severity, and duration of seizures.
• Adverse effects of anticonvulsant drugs include rapid cessation effect of administration of these drugs and liver and serum enzymes induction.
• GABA (Gamma aminobutyric acid) is the major inhibitory NT in the CNS.
• GABA is considered our natural “Valium-like” NT.
• GABA is produced mostly in the brain from glutamic acid/glutamate and needs Vitamin B6 for its synthesis.
• GABA plays an important role in behavior, cognition, and the body response to stress.
• Rare adverse effects of Felbamate include generalized tremor and/or keratoconjunctivitis sicca (dry eye) in dogs.
• Adverse effects of Felbamate include sedation, ataxia, and anorexia.
• There is not enough data for cats.
• The cost of Zonisamide can be a problem for dogs.
• Zonisamide is particularly useful in cases with brain tumor or cerebral infarct due to its no-sedation effect.
• Adverse effects of Zonisamide include sedation, ataxia, and anorexia.
• Adverse effects of Felbamate include liver dysfunction in dogs and rare cases of reversible bone marrow depression (condition: thrombocytopenia or leucopenia) in dogs.
• Felbamate is administered orally, twice a day.
• Felbamate is used as the sole anticonvulsant for patients with local and generalized seizures.
• Felbamate is particularly useful in cases with brain tumor or cerebral infarct due to its no-sedation effect.
• Felbamate is used as an adjunctive therapy for refractory canine epilepsy and as the sole anticonvulsant for patients with local and generalized seizures.
• The mechanism of action of Felbamate is the induction of neural hyperpolarization through inhibition of voltage-dependent Na+ and Ca++ channels.
• Felbamate is used as an adjunctive therapy for refractory canine epilepsy less often in cats.
• The cost of Felbamate can be a problem for dogs.
• Zonisamide is used as an adjunctive therapy for refractory canine epilepsy and as the sole anticonvulsant for patients with local and generalized seizures.
• Barbiturates are not useful for terminating an ongoing seizure because the time span from administration until the onset of effect is too long (~ 20 min).
• Zonisamide inhibits Na+ and Ca++ channels and induces hyperpolarization.
• Unconventional drugs such as Potassium Bromide, Gabapentin, and Levetiracetam inhibit Na+ channels and induce hyperpolarization.
• Therapeutic uses of barbiturates include long-term control of seizures and they are administered orally.
• When given orally