Carbamazepine in phenobarbital-nonresponders: experience with ten preterm infants

Hoppen, Thomas; Elger, Christian E.; Bartmann, Peter

doi:10.1007/s004310100760

Cited by 13 publications

(6 citation statements)

References 10 publications

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“…Its use in this population has been reported previously only in two studies in term 20 and preterm neonates. 21 Consistent with these reports, none of the 17 patients in our cohort treated with CBZ as neonates and infants experienced any gastrointestinal, hepatic, hematologic, renal, or dermatologic side effects. We used a low dose of CBZ; however, since the dose was not subsequently adjusted for weight, it is possible that even lower doses may be effective.…”

Section: Discussionsupporting

confidence: 90%

“…Although, CBZ, a sodium‐channel blocker, has been used in adults and children for >30 years with an excellent therapeutic and side effect profile, it is seldom used in newborns. Its use in this population has been reported previously only in two studies in term and preterm neonates . Consistent with these reports, none of the 17 patients in our cohort treated with CBZ as neonates and infants experienced any gastrointestinal, hepatic, hematologic, renal, or dermatologic side effects.…”

Section: Discussionsupporting

confidence: 83%

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Rapid and safe response to low‐dose carbamazepine in neonatal epilepsy

et al. 2016

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 83%

Rapid and safe response to low‐dose carbamazepine in neonatal epilepsy

et al. 2016

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“…Preliminary studies of antiepileptic drugs other than phenobarbital and phenytoin have shown only modest efficacy in smaller cohorts of neonates, although sufficiently powered randomized trials are needed to conclusively demonstrate whether any of these drugs are truly effective. 7,10,32,46,64 The lack of evidence-based treatment recommendations, coupled with the paucity of data regarding the underlying pathophysiology of neonatal seizures, has made their current management far from optimal.…”

Section: Neonatal Seizures Are a Common Problem With Inadequate Treatmentioning

confidence: 99%

The bumetanide-sensitive Na-K-2Cl cotransporter NKCC1 as a potential target of a novel mechanism-based treatment strategy for neonatal seizures

Kahle¹,

Staley

2008

FOC

108

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Seizures that occur during the neonatal period do so with a greater frequency than at any other age, have profound consequences for cognitive and motor development, and are difficult to treat with the existing series of antiepileptic drugs. During development, γ-aminobutyric acid (GABA)ergic neurotransmission undergoes a switch from excitatory to inhibitory due to a reversal of neuronal chloride (Cl–) gradients. The intracellular level of chloride ([Cl–]i) in immature neonatal neurons, compared with mature adult neurons, is about 20–40 mM higher due to robust activity of the chloride-importing Na-K-2Cl cotransporter NKCC1, such that the binding of GABA to ligand-gated GABAA receptor-associated Cl– channels triggers Cl– efflux and depolarizing excitation. In adults, NKCC1 expression decreases and the expression of the genetically related chloride-extruding K-Cl cotransporter KCC2 increases, lowering [Cl–]i to a level such that activation of GABAA receptors triggers Cl– influx and inhibitory hyperpolarization. The excitatory action of GABA in neonates, while playing an important role in neuronal development and synaptogenesis, accounts for the decreased seizure threshold, increased seizure propensity, and poor efficacy of GABAergic anticonvulsants in this age group. Bumetanide, a furosemide-related diuretic already used to treat volume overload in neonates, is a specific inhibitor of NKCC1 at low doses, can switch the GABA equilibrium potential of immature neurons from depolarizing to hyperpolarizing, and has recently been shown to inhibit epileptic activity in vitro and in vivo in animal models of neonatal seizures. The fundamental role of NKCC1 in establishing excitatory GABAergic neurotransmission in the neonate makes it a tempting target of a novel mechanism-based anticonvulsant strategy that could utilize the well-known pharmacology of bumetanide to help treat neonatal seizures.

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“…CBZ levels dropped precipitously in 15 days, most likely from autoinduction, which also occurs in older children. Hoppen and coworkers (46) used CBZ in 10 preterm infants who had failed therapy with Pb. The initial dose was 7 to 10 mg/kg and was increased up to 23 mg/kg if seizures continued.…”

Section: Carbamazepine (Cbz)mentioning

confidence: 99%