Neonates phenobarbital

The answer is d. (Katzung, pp 411, 1029.) An increased incidence of spina bifida may occur with the use of valproic acid during pregnancy Cardiovascular, orofacial, and digital abnormalities may also occur. The main issue with the use of phenobarbital or primidone (metabolite is phe-nobarbital) for the fetus is neonatal dependence on barbiturates. 

Phenobarbital is the drug of choice for neonatal seizures, but in other situations it is reserved for patients who have failed other AEDs. 

With some drugs, particularly those with a long half life, a loading dose may be useful in order to achieve a therapeutic level more rapidly. For example, the half-life of phenobarbital in the neonate is long, approximately 120 hours, with steady-state concentrations achieved in two to three weeks. A slowly-infused loading dose can be efficacious in achieving seizure control within minutes, typically followed by maintenance infusion and subsequent transition to oral therapy daily. 

Phenobarbital Enhances phasic GABAa receptor responses reduces excitatory synaptic responses Nearly complete absorption not significantly bound to plasma proteins peak concentrations in Vi to 4 h no active metabolites tjy2 varies from 75 to 125 h Generalized tonic-clonic seizures, partial seizures, myoclonic seizures, generalized seizures, neonatal seizures, status epilepticus Toxicity Sedation, cognitive issues, ataxia, hyperactivity Interactions Valproate, carbamazepine, felbamate, phenytoin, cyclosporine, felodipine, lamotrigine, nifedipine, nimodipine, steroids, theophylline, verapamil, others... 

Another consideration for the neonate is whether or not the mother was receiving drugs (such as phenobarbital) that can induce early maturation of fetal hepatic enzymes. In this case, the ability of the neonate to metabolize certain drugs will be greater than expected, and one may see less therapeutic effect and lower plasma drug concentrations when the usual neonatal dose is given. 

It is not surprising that infant L. suffered diffuse encephalopathy (brain disorder), a cerebral infarction, and seizures during the neonatal period (Yager, 2002). Both asphyxia and hypoglycemia are injurious to the brain. The treatment for seizures consists of providing normal metabolic substrates (e.g., glucose) and appropriate anticonvulsant therapy (phenobarbital), as was done in the present case. The long-term treatment for the child s developmental disabilities is complex and involves the skills of many members of the health care team. 

Two neonates whose mothers had used phencyclidine during pregnancy had jitteriness, hypertonicity, vomiting, and in one case diarrhea (25). Both had phencyclidine in the urine. Both remained jittery and slightly hypertonic despite treatment with phenobarbital. One was microcephalic. 

The major route of elimination is hepatic metabolism. The variability in the metabolism and pharmacokinetics in neonates, infants and children necessitates monitoring of drug concentrations in the plasma, particularly when it is co-administered with phenytoin, phenobarbital or rifampin. 

Painter, M.J. Pippenger, C.E. Wasterlein, C. Barmada, M. Pitlick, W. Carter, G. Aberin, S. Phenobarbital and phenytoin in neonatal seizures Metabolism and tissue distribution. Neurology 1981, 31, 1107-1112. 

Spear A M, Hill M R, Mayhew I G et al 1984 Preliminary study on the pharmacokinetics of phenobarbital In the neonatal foal. Equine Veterinary Journal 16 368-371... 

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