Pharmacotherapy for Seizures in Neonates with Hypoxic Ischemic Encephalopathy

Seizures are common in neonates with moderate and severe hypoxic ischemic encephalopathy (HIE) and are associated with worse outcomes, independent of HIE severity. In contrast to adults and older children, no new drugs have been licensed for treatment of neonatal seizures over the last 50 years, because of a lack of controlled clinical trials. Hence, many antiseizure medications licensed in older children and adults are used off-label for neonatal seizure, which is associated with potential risks of adverse effects during a period when the brain is particularly vulnerable. Phenobarbital is worldwide the first-line drug and is considered standard of care, although there is a limited evidence base for its efficacy. Second-line agents include phenytoin, benzodiazepines, levetiracetam, and lidocaine. These drugs are discussed in more detail along with two emerging drugs (bumetanide and topiramate). More safety, pharmacokinetic, and efficacy data are needed from well-designed clinical trials to develop safe and effective antiseizure regimes for the treatment of neonatal seizures in HIE

Oxygen in metabolic dysfunction and its therapeutic relevance

Significance: In recent years, a number of studies have shown altered oxygen partial pressure at a tissue level in metabolic disorders, and some researchers have considered oxygen to be a (macro) nutrient. Oxygen availability may be compromised in obesity and several other metabolism-related pathological conditions, including sleep apnea-hypopnea syndrome, the metabolic syndrome (which is a set of conditions), type 2 diabetes, cardiovascular disease and cancer. Recent Advances: Strategies designed to reduce adiposity and its accompanying disorders have been mainly centered on nutritional interventions and physical activity programs. However, novel therapies are needed since these approaches have not been sufficient to counteract the worldwide increasing rates of metabolic disorders. In this regard, intermittent hypoxia training and hyperoxia could be potential treatments through oxygen-related adaptations. Moreover, living at high altitude may have a protective effect against the development of abnormal metabolic conditions. In addition, oxygen delivery systems may be of therapeutic value for supplying the tissue-specific oxygen requirements. Critical Issues: Precise in vivo methods to measure oxygenation are vital to disentangle some of the controversies related to this research area. Furthermore, it is evident that there is a growing need for novel in vitro models to study the potential pathways involved in metabolic dysfunction in order to find appropriate therapeutic targets. Future directions: Based on the existing evidence, it is suggested that oxygen availability has a key role in obesity and related comorbidities. Oxygen should be considered in relation to potential therapeutic strategies in the treatment and prevention of metabolic disorders