Current pharmaceutical design
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Sudden cardiac arrest is a leading cause of death worldwide with survival rates still remaining suboptimal. Unfortunately, most cardiac arrest patients, who achieve return of spontaneous circulation (ROSC), develop a multi-faceted post-cardiac arrest syndrome, including post-cardiac arrest brain injury, myocardial dysfunction, and systemic ischemia/reperfusion response. ⋯ In this regard, EPO represents a promising agent in the cardiac arrest setting, based on a therapeutic strategy that focuses on the post-resuscitation phase. This review aims to provide a comprehensive account of EPO's role in the treatment of each individual component of post-cardiac arrest syndrome.
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The neuropathic pain syndrome is complex. Current drugs to treat neuropathic pain, including anticonvulsivants and antidepressants, fail in up to 40-50% of the patients, while in the rest of them total alleviation is not normally achieved. Increased research advances in the neurobiology of neuropathic pain have not translated in more successful pharmacological treatments by the moment, but recent progress in the experimental methods available for this purpose could result in significant advances in the short term. ⋯ Following this strategy, neurotrophic factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been postulated as potential pharmacological targets to treat neuropathic pain. In addition, during the last few years, strong scientific evidences point to novel neurotrophic factors, such as pleiotrophin (PTN), as important factors to limit neuropathic pain development because of their remodeling and angiogenic actions in the injured area. This review focuses on recent research advances identifying new pharmacological targets in the treatment of the cause, not only the symptoms, of neuropathic pain.
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Opioid medications are increasingly used to treat chronic pain. Opioid-associated respiratory depression, and their potential to cause nocturnal apneas, is increasingly recognized as a major contributor to nocturnal hypoxemia and sleep-disordered breathing. ⋯ This article reviews the salient features of the physiologic control of respiration and sleep, and the role opioids play in altering that regulation. Additionally, we summarize the evidence regarding the association between opioid use and sleep-disordered breathing and explore treatment modalities for opioid-associated nocturnal respiratory depression and apneas.
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Severe asthma is a complex and heterogeneous phenotype characterized by persistent symptoms and poor control. While some patients respond to high doses of inhaled corticosteroids in combination with long-acting beta-agonists, a significant subset require oral corticosteroids to achieve symptom control. ⋯ The article then reviews alternative therapeutic strategies including macrolide antibiotics, biologic agents, modulators of signal transduction pathways and bronchial thermoplasty. The challenge remains to determine the appropriate phenotype for each therapeutic strategy in view of the heterogeneity of severe asthma.
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Hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep through stabilization of sleep promoting GABAergic and wake promoting cholinergic/monoaminergic neural pathways. Hypocretin also influences other physiologic processes such as metabolism, appetite, learning and memory, reward and addiction, and ventilatory drive. ⋯ However, antagonizing a system that regulates the sleep-wake cycle while also influencing non-sleep physiologic processes may create an entirely different but equally concerning side-effect profile such as transient loss of muscle tone (i.e. cataplexy) and a dampened respiratory drive. In this review, we will discuss the discovery of hypocretin and its receptors, hypocretin and the sleep-wake cycle, hypocretin antagonists in the treatment of insomnia, and other implicated functions of the hypocretin system.