Seizures develop when a massive number of neurons depolarize repetitively. Specific drugs stop and prevent seizures by avoiding the factors that initiate the chain reaction that ultimately leads to repetitive massive neuronal depolarization. Antiepileptic drugs act at different levels of the chain reaction that leads to neuronal depolarization. Antiepileptic drugs act by: (1) preventing the sodium channel from opening; (2) facilitating the passage of chloride ions into the cell; (3) inhibiting T-calcium currents; and (4) antagonizing one or more types of glutamate receptors. Glutamate receptors are N-methyl-D-aspartate [NMDA], alpha-amino-3-hydroxy-methyl-4-isoxazole-propionic acid [AMPA], or kainite. These receptors facilitate the passage of calcium and sodium into the cell.
Antiepileptic drugs are not indicated in all neonates with convulsions. Convulsions that stop with etiology-specific therapy and those that are brief and infrequent may not warrant antiepileptic drugs. The following factors should be considered prior to the initiation of antiepileptic drugs in neonates with seizures without etiology-specific therapy: (1) clinical consequences, and duration and frequency of the seizure; (2) natural history of the disorder; and (3) possible side effects of the seizures and the antiepileptic drugs.
The decision to use antiepileptic drugs is even more uncertain in the absence of electroencephalographic-confirmed seizures. Most physicians tend to use antiepileptic drugs for prolonged and recurrent focal and clonic paroxysmal motor events, and avoid using antiepileptic drugs for myoclonus provoked by stimulation or for generalized tonic posturing or automatisms provoked by stimulation or suppressed by restraint. The use of antiepileptic drugs for brief and infrequent myoclonus, focal clonic and tonic paroxysmal motor events, or generalized tonic posturing or automatisms is controversial.
Phenobarbital is the drug of choice to treat convulsions in neonates. Phenobarbital acts on sodium current and GABA receptors. The loading dose is 20 mg/kg. It should be infused intravenously at a rate no faster than 1 mg/kg per minute. If the seizure persists 10 minutes after completing the loading dose, a second dose of 20 mg/kg should be administered. If the seizure stops, no further antiepileptic medication is given and a phenobarbital level is taken after 6 hours or if seizures recur. The maintenance dose of phenobarbital is 3 to 5 mg/kg per day.