Current pharmaceutical design
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Sepsis and septic shock are known to prompt multiple organ failure including cardiac contractile dysfunction, which is typically referred to as septic cardiomyopathy. Among various theories postulated for the etiology of septic cardiomyopathy, mitochondrial injury (both morphology and function) in the heart is perceived as the main culprit for reduced myocardial performance and ultimately heart failure in the face of sepsis. ⋯ Here we will briefly summarize the recent experimental and clinical progress on myocardial mitochondrial morphology and function in sepsis, and discuss possible underlying mechanisms, as well as the contemporary interventional options.
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Opioids are the cornerstone of the management of cancer pain. However, the development of adverse effects may compromise the opioid response. They include nausea and vomiting, constipation, drowsiness, sleep disorders, cognitive dysfunction, myoclonus, pruritus, dysuria, dependence and the development of aberrant behaviors, respiratory depression, and some endocrine responses. ⋯ Intensity of adverse effects tend to decrease with continuous use. However, they may be persistent and may require symptomatic treatment or more complex treatment including alternative strategies for pain management.
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Multimodal, non-opioid based analgesia has become the cornerstone of ERAS protocols for effective analgesia after spinal surgery. Opioid side effects, dependence and legislation restricting long term opioid use has led to a resurgence in interest in opioid sparing techniques. The increasing array of multimodal opioid sparing analgesics available for spinal surgery targeting novel receptors, transmitters, and altering epigenetics can help provide an optimal perioperative experience with less opioid side effects and long-term dependence. ⋯ Such mechanisms are complex, dynamic and responsive to environment. Alterations that occur can affect the pathophysiology of pain management at a DNA level, modifying perceived pain relief. In this review, we provide a brief overview of epigenetics of pain, systemic local anesthetics and neuraxial techniques that continue to remain useful for spinal surgery, neuropathic agents, as well as other common and less common target receptors for a truly multimodal approach to perioperative pain management.
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650 millions of adults are obese worldwide - in the US alone, forty percent of the adults are obese. Although the obesity pandemic is constantly expanding at very high costs for health care systems, the currently available options of pharmacotherapy for obesity are rather limited. ⋯ However, the understanding of the pathophysiology of obesity has been steadily improving and new, promising drugs targeting various selective obesityassociated and energy-homeostasis-related pathways are now available. When lifestyle changes alone fail to combat, then additional pharmacotherapy with an acceptable efficacy and safety profile could provide a useful therapeutic option.
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Review
Novel Findings and Therapeutic Targets on Cardioprotection of Ischemia/ Reperfusion Injury in STEMI.
Acute ST-segment elevation myocardial infarction (STEMI) remains a leading cause of morbidity and mortality around the world. A large number of STEMI patients after the infarction gradually develop heart failure due to the infarcted myocardium. Timely reperfusion is essential to salvage ischemic myocardium from the infarction, but the restoration of coronary blood flow in the infarct-related artery itself induces myocardial injury and cardiomyocyte death, known as ischemia/reperfusion injury (IRI). ⋯ Therefore, additional cardioprotection is required to prevent the heart from IRI. Although many mechanical conditioning procedures and pharmacological agents have been identified as effective cardioprotective approaches in animal studies, their translation into the clinical practice has been relatively disappointing due to a variety of reasons. With new emerging data on cardioprotection in STEMI over the past few years, it is mandatory to reevaluate the effectiveness of "old" cardioprotective interventions and highlight the novel therapeutic targets and new treatment strategies of cardioprotection.