Most infants with hypocalcemia are asymptomatic, and early, mild hypocalcemia often resolves without treatment. Because neonatal jitteriness can also occur with hypoglycemia, a blood glucose level should also be determined at the same time to help differentiate possible causes. Cognitive Function The effect of maternal epilepsy on IQ in the offspring has been studied. Small head size can occur in neonates prenatally exposed to antiepilepsy drugs.
Most infants exposed to only a single drug have normal intellectual capacity, and the smaller head size does not seem to be related to cognitive functioning in adulthood. On the basis of these results, pregnant women with epilepsy should not be concerned that taking phenytoin will result in lower IQ for the baby, but they must be aware that learning problems may occur.
It is important to manage the seizure activity of pregnant women while minimizing effects on the fetus and neonate. The major emphasis is prevention and counseling young women with epilepsy about the disease and use of antiepilepsy drugs during pregnancy.
Women with epilepsy should be taught that even without medication for their epilepsy, they have a higher risk of delivering an infant with congenital malformation and cognitive impairment.
Although the exact mechanism is unknown, it is theorized that genetic factors contribute to the increased prevalence of malformations in infants born to mothers with epilepsy independent of maternal medications. However, adult rates of metabolism may be achieved for some drugs eg, barbiturates, phenytoin 2 to 4 wk postnatally.
CYP activity can also be induced reducing drug concentrations and effect or inhibited augmenting concentrations and effect by coadministered drugs. These drug interactions may lead to drug toxicity when CYP activity is inhibited or an inadequate drug level when CYP activity is induced. Kidneys, lungs, and skin also play a role in the metabolism of some drugs, as do intestinal drug-metabolizing enzymes in neonates. Phase II metabolism varies considerably by substrate.
Maturation of enzymes responsible for bilirubin and acetaminophen conjugation is delayed; enzymes responsible for morphine conjugation are fully mature even in preterm infants.
Drug metabolites are eliminated primarily through bile or the kidneys. Renal elimination depends on Plasma protein binding GFR Tubular secretion All of these factors are altered in the first 2 yr of life. This approach is practical but not ideal.
Even within a population of similar age and weight, drug requirements may differ because of maturational differences in absorption, metabolism, and elimination. Thus, when practical, dose adjustments should be based on plasma drug concentration however, plasma drug concentration may not reflect the drug concentration in the target organ.
Unfortunately, these adjustments are not feasible for most drugs. Meeting the demand for pediatric clinical trials. Sci Transl Med 6 This is accomplished by reducing the amplitude of sodium-dependent action potentials through enhancing steady state inactivation. Sodium channels exist in three main conformations: Phenytoin binds preferentially to the inactive form of the sodium channel.
Because it takes time for the bound drug to dissociate from the inactive channel, there is a time dependent block of the channel. Since the fraction of inactive channels is increased by membrane depolarization as well as by repetitive firing, the binding to the inactive state by phenytoin sodium can produce voltage-dependent, use-dependent and time-dependent block of sodium-dependent action potentials.
This includes the reduction of post-tetanic potentiation at synapses which prevents cortical seizure foci from detonating adjacent cortical areas. Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of generalized tonic-clonic seizures. A small increase in dose may lead to a large increase in drug concentration as elimination becomes saturated. The time to reach steady state is often longer than 2 weeks.
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© Copyright 2017 Phenytoin kinetics infant. Epilepsy and Pregnancy: Maternal and Fetal Effects of Phenytoin.