Pharmacologic therapies for the low cardiac output syndrome in children after cardiac surgery: evidence of their efficacy and trends in their use

The low cardiac output syndrome describes the phenomenon of the reduction of cardiac output that can occur following cardiac surgery requiring cardiopulmonary bypass. If unrecognized or untreated, this condition can result in significant morbidity and mortality. Along with non-pharmacologic therapies, pharmacologic agents used to help manage the low cardiac output syndrome include catecholamine inotropes, inodilators, systemic vasodilators, pulmonary vasodilators, and other classes of medications. We summarize the rationale and key evidence supporting the use of these therapies in children. In addition, utilizing provider surveys and registry reviews, we describe the current trends in the use of these medications and the variation demonstrated between providers and centers. Given the heterogeneous etiology of low cardiac output syndrome, successful management requires that pharmacologic therapies be tailored to the physiologic derangements of each patient.

Iridoid analysis by different analytical techniques and its role as pharmacologic agents- A review

Iridoids are monoterpenoids classed with a cyclopentanopyran framework and are detected in various plants and certain special animals. In plants, it exists as glycosides, generally bound to glucose. Around six hundred iridoid glycosides are available in fifty-seven families of plants. Iridoids are abundant in dicotyledonous plants belonging to the Diervillaceae, Loganiaceae, Apocynaceae, Scrophulariaceae, Lamiaceae, and Rubiaceae families. Analytical techniques like chromatography, NMR, UPLC, etc., are used for the identification, separation, and estimation of either herbal extracts or formulations of iridoids. Advanced analytical techniques are very useful for precise and accurate quantification of active ingredients that are responsible for therapeutic effects, and they can be achieved by a developed and validated robust analytical method. Iridoids have shown diverse pharmacological properties. Some of the important activities are immunomodulatory, neuroprotective, anti-inflammatory, hepatoprotective, and cardio-protective effects. The other important activities are antimicrobial, antioxidant, hypoglycemic, hypolipidemic, anticancer, choleretic, antispasmodic, and purgative activities attributed to iridoids. There were not many efforts made in the past to gather and review the literature on various aspects of iridoids. This review article has collected a myriad of literature on old and advanced analytical techniques, including method development and validation of methods for quantitative and qualitative analysis of iridoids. The review also emphasizes the role of iridoids in the prevention of various ailments.

The Monoterpenoid Perillyl Alcohol: Anticancer Agent and Medium to Overcome Biological Barriers

Perillyl alcohol (POH) is a naturally occurring monoterpenoid related to limonene that is present in the essential oils of various plants. It has diverse applications and can be found in household items, including foods, cosmetics, and cleaning supplies. Over the past three decades, it has also been investigated for its potential anticancer activity. Clinical trials with an oral POH formulation administered to cancer patients failed to realize therapeutic expectations, although an intra-nasal POH formulation yielded encouraging results in malignant glioma patients. Based on its amphipathic nature, POH revealed the ability to overcome biological barriers, primarily the blood–brain barrier (BBB), but also the cytoplasmic membrane and the skin, which appear to be characteristics that critically contribute to POH’s value for drug development and delivery. In this review, we present the physicochemical properties of POH that underlie its ability to overcome the obstacles placed by different types of biological barriers and consequently shape its multifaceted promise for cancer therapy and applications in drug development. We summarized and appraised the great variety of preclinical and clinical studies that investigated the use of POH for intranasal delivery and nose-to-brain drug transport, its intra-arterial delivery for BBB opening, and its permeation-enhancing function in hybrid molecules, where POH is combined with or conjugated to other therapeutic pharmacologic agents, yielding new chemical entities with novel mechanisms of action and applications.

Botulinum Toxin Therapy in Writer’s Cramp and Musician’s Dystonia

Task-specific focal dystonia is characterized by muscle contraction(s) during a specific task, resulting in abnormal postures or movements. Specifically, writer’s cramp involves the upper extremity during the act of writing. Musician’s dystonia has a highly variable presentation, and thus makes therapeutic options more limited. Treatments include oral pharmacologic agents, neuromodulation, surgery and, most often, botulinum toxin (BoNT) injection. Selection of target muscles for toxin injection continues to be an area of active research for these task-specific movements. We present a review of the literature selected from a predefined search of the MEDLINE and ClinicalTrials.gov databases. We include six controlled studies of botulinum toxin for the management of writer’s cramp and focal task-specific dystonia (FTSD), including musician’s dystonia. Overall, 139 patients were included across all studies, with 99 individuals injected for writer’s cramp and the remaining 40 individuals with FTSD. The age range of all patients was 18–80 years old. We included studies that utilized only the BoNT-A serotype. These studies utilized various severity scales to quantify response to toxin injection, with ratings of instrument or pen control included as subjective ratings. Of the included 139 patients in this review, pooled data for toxin response show that 73% of patients who received the drug demonstrated improvement. Specific techniques for muscle localization and targeting were difficult to study as variable methods were employed. This remains an area of ongoing exploration.

Anesthesia-Induced Oxidative Stress: Are There Differences between Intravenous and Inhaled Anesthetics?

Agents used for the induction of anesthesia have been shown to either promote or mitigate oxidative stress. A fine balance between the presence of reactive oxygen species (ROS) and antioxidants is crucial for the proper normal functioning of the cell. A basal concentration of ROS is essential for the manifestation of cellular functions, whereas disproportionate levels of ROS cause damage to cellular macromolecules such as DNA, lipids, and proteins, eventually leading to necrosis and apoptosis. Increased ROS has been linked with numerous illnesses, such as cardiovascular, immune system, liver, and kidney, and has been shown to promote cancer and accelerate aging. Knowledge of the various pharmacologic agents that increase or reduce oxidative stress may promote a safer way of inducing anesthesia. Furthermore, surgery itself leads to increased ROS production and ischemia/reperfusion injury. Indeed, increased perioperative oxidative stress has been correlated with increased postoperative complications and prolonged recovery. Anesthesiologists care for patients during the whole spectrum of perioperative care and thus are in a unique position to deliver countermeasures to oxidative stress. Using preferentially an induction agent which reduces oxidative stress might lead to better clinical outcomes and fewer postoperative complications. Propofol has been shown in several studies to reduce oxidative stress, which reduces postoperative complications and leads to a faster recovery, and thus might represent the preferred induction agent in the right clinical setting.

Risk of drug-induced cardiac arrhythmia during COVID-19 therapeutic treatment

Therapeutic treatment of severe COVID-19 infection involves the administration of multiple pharmacologic agents to reduce the risk of serious complications; this may result in drug interactions and possible adverse reactions and induced cardiotoxicity. The risk–benefit ratio associated with the use of medications to treat COVID-19 should be carefully monitored. In addition, the severe COVID-19 patient may experience cardiac damage, and alteration of normal cardiac electrophysiology function. Severe COVID-19 with cardiac involvement and the risk of drug-induced adverse reactions may cause cardiac arrhythmias, including long qt syndrome, which in some cases may lead to sudden death. In this short review we briefly review the pharmacological agents used to treat severe COVID-19 with increased risk of causing long qt forms.

Secondary Prevention of Ischemic Stroke

After an ischemic stroke is diagnosed, a diagnostic evaluation ensues to determine the mechanism of the stroke and contributing risk factors. The appropriate antithrombotic is selected in accordance with the mechanism of the stroke, and the contributing risk factors are treated with pharmacologic agents and lifestyle changes. This chapter discusses the selection of antithrombotic medication, medical treatment, and lifestyle changes for contributing risk factors.

Neuropharmacology of Sleep

Sleep disorders often respond to both pharmacologic agents and nonpharmacologic therapies. This chapter reviews the pharmacology of and indications for specific sleep agents. Most of the agents approved by the US Food and Drug Administration for insomnia, with the exception of antidepressants and ramelteon, modulate the function of the γ‎-aminobutyric acid (GABA)-A receptor complex. The ventrolateral preoptic nucleus (VLPO) has a critical role in sleep initiation and maintenance. GABA is the primary inhibitory neurotransmitter of the VLPO. Medications used for sleep promotion include benzodiazepines, chronobiotics, sedating antidepressants, histamine blockers, and γ‎-hydroxybutyric acid.

Neuroprotective Agents for Neonates with Hypoxic-Ischemic Encephalopathy

Hypoxic-ischemic encephalopathy (HIE) remains a significant source of long-term neurodevelopmental impairment despite overall improvements in survival without disability in neonates who undergo therapeutic hypothermia. Each phase in the evolution of hypoxic-ischemic injury presents potential pharmacologic targets for neuroprotective agents. Melatonin is a promising emerging therapy for early phases of ischemic injury, but utility is currently limited by the lack of pharmaceutical-grade products. Magnesium has been extensively studied for its neuroprotective effects in the preterm population. Studies in neonates with HIE have produced mixed outcomes. Erythropoietin use in HIE with or without therapeutic hypothermia appears to be safe and may provide additional benefit. Dexmedetomidine, N-acetylcysteine, xenon, and topiramate all have promising animal data, but need additional human trials to elucidate what role they may play in HIE. Frequent review of existing literature is required to ensure provision of evidence-based pharmacologic agents for neuroprotection following HIE.