Use Of Pharmacological Agents Research Articles

Purinergic Receptors Profile in the ARPKD Cystic Epithelia

Polycystic kidney diseases (PKD) are a group of inherited nephropathies marked with the formation of fluid‐filled cysts along the nephron. Growing evidence suggests that autocrine and paracrine effects of purinergic signaling via P2 receptors could detrimentally contribute to cyst expansion. However, little is known about purinergic signaling in renal cyst epithelium, which is characterized by loss of polarity, dedifferentiation and other abnormalities which can lead to purinergic signaling remodeling. We have proposed that ATP via associated intracellular signaling can contribute to cystogenesis by modulation of calcium influx. PCK/CrljCrl‐Pkhd1pck/CRL (PCK) rat, an established model of ARPKD, was used here to test this hypothesis. The cystic fluid of PCK rats and their cortical tissues exhibited significantly higher levels of ATP compared to Sprague Dawley (SD) rat kidney cortical interstitium as assessed by highly sensitive for ATP enzymatic biosensors (211±55 vs 1082±147 nM for SD and PCK cortex correspondingly, and 2,078±391 nM for cystic fluid). Confocal calcium imaging of the freshly isolated cystic monolayers revealed a stronger response to ATP in a higher range of concentrations (above 100 μM). The removal of extracellular calcium results in the absence of ATP evoked transient, which pointed towards the extracellular (ionotropic) calcium entry in cyst‐lining cells rather than the metabotropic P2Y‐mediated internal depot. Application of iso‐PPADS (a non‐selective P2X antagonist) resulted in partial blockade of ATP response (calcium release after ATP was 30.1 ± 0.9, 22.2 ± 1.8 and 19.5 ± 3.2 a.u. in control, after incubation with iso‐PPADS, and after washout, respectively) indicating the contribution of P2X4 purinoreceptor in the cystic monolayer. Next, to specifically assess the role of P2X7 in the ATP‐mediated calcium influx, we employed AZ10606120, a potent P2X7 receptor antagonist. Application of AZ10606120 (5 μM) resulted in a bunted calcium response to ATP (32.4 ± 2.2, 13.5 ± 6.4, and 11.1 ± 3.1 a.u. of total calcium release in control, after incubation with AZ10606120, and after washout, respectively), which corroborates the commonly hypothesized role of P2X7 in cyst development. Further use of pharmacological agents (α,β‐methylene‐ATP, 5‐BDBD, and NF449) allowed to narrow down potential candidate receptors and suggested a significant involvement of the P2X4 and/or P2X7 signaling axis in the regulation of cytosolic calcium level in the cystic epithelia. In conclusion, our ex vivo study provides direct evidence that the profile of P2 receptors is altered in the ARPKD cystic epithelia towards the prevalence of P2X4 and/or P2X7 receptors, which opens new avenues for the treatment of this disease.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Pharmacotherapy in Acutely Anemic Jehovah's Witnesses: An Evidence-Based Review.

To determine the pharmacological treatment methods available to anemic Jehovah's Witnesses (JW). MEDLINE and PubMed were searched from inception through February 2018 using the search terms Jehovah's Witnesses, treatment, erythropoietin, hemoglobin-based oxygen carrier, Sanguinate, Hemopure, bleeding, and anemia. All clinical trials, cohort studies, case-control studies, and observational trials involving pharmacotherapy in anemic JW patients were evaluated. Case reports and bibliographies were also analyzed for inclusion. Two studies involving the use of erythropoietin (EPO) and one study involving recombinant factor VIIa were included. Information was also included from other pharmacotherapeutic modalities that had case report data only. Current published evidence is limited with regard to evidence-based management of JW patients. High-dose EPO, intravenous iron supplementation, and hemostatic agents have demonstrated good clinical outcomes in case reports. EPO doses as high as 40 000 units daily have been advocated by some experts; however, pharmacokinetic studies do not support dose-dependent effects. Hemoglobin-based oxygen carriers (HBOCs) are currently not Food and Drug Administration approved. They are available through expanded access programs and may represent a lifesaving modality in the setting of severe anemia. There are currently not enough data to make definitive recommendations on the use of pharmacological agents to treat severe anemia in the JW population. Further evidence utilizing EPO and HBOCs will be beneficial to guide therapy.

Abstract P3-12-13: Breast atypical hyperplasia and guideline compliance

Abstract Background: Atypical hyperplasia of the breast is a high-risk benign lesion that is found in approximately 10% of benign breast biopsies[1]and confers a risk for future breast cancer[2]. The American Society of Clinical Oncology guideline states that pharmacologic risk reduction with the use of a selective estrogen receptor modulator or an aromatase inhibitor should be discussed with women with a 5-year projected absolute risk of breast cancer of 1.7% or higher[3]. The NCCN guideline for risk reduction recommends consideration of risk-reduction interventions, including the use of pharmacologic agents in women with a 5-year risk of 1.7% or higher and a life expectancy of 10 years or longer [4] .The majority of women with atypical hyperplasia meet this risk criterion with their cumulative risk of approximately 1% per year. Method: We retrospectively reviewed excisional biopsy pathology reports between January 2016 and June 2016 with the diagnosis of atypical ductal or lobular hyperplasia to identify patients with pure atypical hyperplasia. Medical records of these patients were then reviewed to identify the percentage of patients referred to a medical oncologist for chemoprevention discussion and the percentage of patients who received chemoprevention following excisional biopsy. Results: Two hundred seventy six patients with the diagnosis of atypical ductal or lobular hyperplasia were identified. Two hundred and sixteen patients were excluded from the analysis due to the presence of other histologies such as carcinoma in situ and invasive carcinoma. Medical records of the remaining sixty patients with pure atypical hyperplasia were reviewed. Eighteen patients' charts were unavailable for review. All of the remaining forty two patients had a 5-year breast cancer risk of 1.7% or higher. Five of these patients (8.3%) were referred to a medical oncologist for chemoprevention discussion. Two of these five patients (2.3%) received chemoprevention with tamoxifen. For patients who were not referred to medical oncologist, there was one documented discussion of chemoprevention with patient by her surgical oncologist. One patient underwent prophylactic bilateral mastectomies, and therefore, chemoprevention was not recommended. Conclusion: Multidisciplinary strategies need to be implemented to bridge the gap between guidelines and clinical practices which may lead to improved patient outcomes.

Oral Fluid Drug Testing in Pain Management Practice: Factors to Consider Before Choosing the Alternative Biological Matrix.

As the use of pharmacological agents, particularly opioid analgesics, has increased in the past 2 decades, so have the substance abuse risks, along with the prevalence of overdose deaths, addiction, and illicit drug use. Accordingly, close monitoring of patients to ensure medication compliance and to identify improper drug use becomes a critical task for pain-management practitioners. Oral fluid is an emerging biological matrix for clinical drug testing. It offers noninvasive, less hazardous, and directly observable sample collection with minimal potential for adulteration. Oral fluid can be collected multiple times in a short period and shows a stronger correlation with blood than urine concentrations. Usability of oral fluid testing had been limited by the sensitivity of analytical methods. The volume of oral fluid samples is typically much smaller than that of urine samples. Furthermore, oral fluid drug concentrations can be 10- to 100-fold lower than urine concentrations depending on analytes. Recent advances in analytical technologies lead to the growing popularity of oral fluid testing and subsequent need for scientific data to aid in interpretation of oral fluid test results. This review presents preanalytical, analytical, and postanalytical considerations associated with oral fluid drug testing for those contemplating the implementation of this alternative biological matrix in pain-management practice. Comparison with urine testing, collection procedure, drug stability, available technologies, scope of analysis, and drug disposition are discussed. As with other monitoring tools, oral fluid testing has advantages and limitations. The most important consideration is staying informed to use the testing within its capability.

Accelerated Orthodontics–An overview

Orthodontic treatment is the reorganization of skeletal and/or dental tissues. Prolonged treatment duration is one of the main concerns of patients undergoing with fixed orthodontics. This extended orthodontic treatment in such particular cases has several drawbacks to the patients such as increased predisposition to root resorption, dental caries and gingival recession, etc. Consequently, researchers introduced few methods to accelerate the velocity of the tooth movement without any drawbacks. These kind of methods used in orthodontics were popular as accelerated orthodontics. Accelerated orthodontics could be possible by mechanical stimulation or device assisted therapy, surgical therapy and by the use of pharmacological agents. The purpose of the present manuscript was to describe and evaluate the methods used in accelerated orthodontics.

Сontemporary aspects of postoperative analgesia (review)

In this review of the literature on modern drugs and techniques to ensure multicomponent analgesia in surgical wards is presents. The technique of pre-emptive analgesia, which reduces the intensity of postoperative pain and contributes to the prevention of chronic postoperative pain. Clear instructions on the use of pharmacological agents (non-steroidal inflammatory drugs, gabapentin, ketamine) and preventive epidural anaesthesia are given. The characteristic of narcotic and non-narcotic analgesics are available for use after surgery and alsonefopam, flupirtine and gabapentine. The results of the application of the prolonged epidural analgesia using microinfusion elastomeric pumps are presents.

A review of the pharmacological management of sexually offending behaviour in learning disabled offenders

Purpose The management of sexual offending is a major challenge, particularly in men who have an intellectual disability. Psychological therapies have been shown beneficial, and programmes designed for use in the general population have been adapted for use in offenders who have an intellectual disability. There is also a role for pharmacological management, although the quality of evidence for this is noticeably lacking, most likely associated with the ethical and legal issues encountered in conducting well designed and controlled trials in this area. The purpose of this paper is to look at the pharmacological management options available. Design/methodology/approach A literature search of electronic databases was undertaken. Additionally, the references lists for identified papers were examined for any further relevant publications. Findings The two main categories of drugs used in the management of inappropriate sexual behaviour are the testosterone-lowering drugs and the psychotropic drugs. Most trials were open and utilised self-report measures of drug effectiveness, limiting their usefulness. Most trials noted beneficial effect. Side effect profiles and patient adherence can limit the effectiveness of anti-libidinal medication in practice. Originality/value There is very limited evidence available for the use of pharmacological agents in the management of inappropriate sexual behaviour, owing to the lack of adequately controlled clinical trials. New studies are therefore required, particularly of larger sample sizes, longer durations, and examining characteristics of those who benefit from pharmacological treatment, although the ethical issues of conducting such studies is duly acknowledged.

Medical Pharmacology and Therapeutics by Derek G. Waller and Anthony P. Sampson

A thorough and contemporaneous working knowledge of both pharmacology and therapeutics is integral to the current practice of pharmacy, and both disciplines form a significant and rudimentary part of the undergraduate curricula. It is vital that the student is able to formulate scientific rationale for the use of pharmacological agents in the treatment of disease, and that a sound underpinning knowledge of all relevant disciplines enables them to do so. Of equal importance is the ability of the teacher to present essential information about pharmacology and therapeutics as part of an integrated curricula in a way that engages the student and enhances their appreciation of the applicability of these various disciplines to clinical practice. Waller and Sampson’s ‘Medical Pharmacology and Therapeutics’ aims to encourage a deeper understanding of the principals of drug usage by explaining the basic science underpinning clinical application of pharmacological agents. This review seeks to investigate elements that are specific to the needs of the target audience and will explore the potential of this book in achieving those aims.

薬物の最適利用を目指し，製剤研究，DDS創製に取り組む

薬物の最適利用を目指し，製剤研究，DDS創製に取り組む

Effects of Biotin Supplementation During the First Week Postweaning Increases Pancreatic Islet Area, Beta-Cell Proportion, Islets Number, and Beta-Cell Proliferation.

During maturation, pancreatic islets achieve their full capacity to secrete insulin in response to glucose, undergo morphological changes in which alpha-cells decrease and beta-cell mass increases, and they acquire the normal alpha- and beta-cell proportion changes that are important for islet functions later in life. In rodents, the first week of postweaning is critical for islet maturation. Multiple studies have documented the detrimental effects of several conditions on pancreatic maturation; however, few studies have addressed the use of pharmacological agents to enhance islet maturation. Biotin might have a potential action on islet maturation. Pharmacological concentrations of biotin have been found to modify islet morphology and function. In a previous study, we found that mice fed a biotin-supplemented diet for 8 weeks after weaning showed an increase in basal and glucose stimulated insulin secretion, enlarged islet size, and modified islet structure. In the present study, we investigated the effect of biotin on maturation features during the first week postweaning. Female BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet for 1 week after weaning. Compared with the control, biotin-supplemented mice showed an increase in pancreatic islet number and area in addition to an augmented proportion of beta-cells in the islet. These effects were related to an increase in beta-cell proliferation. No differences were found in insulin secretion, blood glucose concentrations, or serum insulin levels. These results indicate that biotin supplementation is capable of affecting beta-cell proliferation and might be a therapeutic agent for establishing strategies for regenerative medicine.

Cognitive Enhancement and Coping in an Australian University Student Sample

Cognitive enhancement (CE) agents are those purported to improve or augment aspects of cognition such as working memory, creativity, and executive function in healthy individuals. CE by university students looking to improve their academic performance, particularly through the use of pharmacological agents (or nootropics), has become an area of increasing interest for researchers. However, studies on the prevalence of, and motivations behind, students’ CE use at Australian universities are limited. This study aimed to contribute a new sample of prevalence data, as well as corroborate previous qualitative research that has suggested that emotion-focused and avoidant coping styles may make students more susceptible to utilizing CE drugs. A sample of N=633 individuals was recruited to complete the “Cognitive Enhancement and Student Lifestyle Survey” online. The key questions of interest concerned students’ enhancement drug usage habits, usage motivations, and coping styles. Analyses found that 6.32% of students indicated lifetime use of prescription CE agents for the purposes of study-related enhancement. Furthermore, dysfunctional coping strategies were associated with an increased likelihood of both lifestyle and prescription CE drug use. Findings from this study refine current understandings of enhancement drug use in Australia and are contextualized in regard to potential avenues for on-campus health interventions and regulatory opportunities. In particular, helping students to maintain manageable stress levels through identifying less harmful coping strategies may prove useful.

Guidelines for Preoperative Fasting for Hospitalized Patients.

Guidelines for Preoperative Fasting for Hospitalized Patients.

Neuropharmacological Targets for Drug Action in Vestibular Sensory Pathways.

The use of pharmacological agents is often the preferred approach to the management of vestibular dysfunction. In the vestibular sensory pathways, the sensory neuroepithelia are thought to be influenced by a diverse number of neuroactive substances that may act to enhance or inhibit the effect of the primary neurotransmitters [i.e., glutamate (Glu) and acetylcholine (ACh)] or alter their patterns of release. This review summarizes various efforts to identify drug targets including neurotransmitter and neuromodulator receptors in the vestibular sensory pathways. Identifying these receptor targets provides a strategic basis to use specific pharmacological tools to modify receptor function in the treatment and management of debilitating balance disorders. A review of the literature reveals that most investigations of the neuropharmacology of peripheral vestibular function have been performed using in vitro or ex vivo animal preparations rather than studying drug action on the normal intact vestibular system in situ. Such noninvasive approaches could aid the development of more accurate and effective intervention strategies for the treatment of dizziness and vertigo. The current review explores the major neuropharmacological targets for drug action in the vestibular system.

Protocol for the management of psychiatric patients with psychomotor agitation

BackgroundPsychomotor agitation (PMA) is a state of motor restlessness and mental tension that requires prompt recognition, appropriate assessment and management to minimize anxiety for the patient and reduce the risk for escalation to aggression and violence. Standardized and applicable protocols and algorithms can assist healthcare providers to identify patients at risk of PMA, achieve timely diagnosis and implement minimally invasive management strategies to ensure patient and staff safety and resolution of the episode.MethodsSpanish experts in PMA from different disciplines (psychiatrists, psychologists and nurses) convened in Barcelona for a meeting in April 2016. Based on recently issued international consensus guidelines on the standard of care for psychiatric patients with PMA, the meeting provided the opportunity to address the complexities in the assessment and management of PMA from different perspectives. The attendees worked towards producing a consensus for a unified approach to PMA according to the local standards of care and current local legislations. The draft protocol developed was reviewed and ratified by all members of the panel prior to its presentation to the Catalan Society of Psychiatry and Mental Health, the Spanish Society of Biological Psychiatry (SEPB) and the Spanish Network Centre for Research in Mental Health (CIBERSAM) for input. The final protocol and algorithms were then submitted to these organizations for endorsement.ResultsThe protocol presented here provides guidance on the appropriate selection and use of pharmacological agents (inhaled/oral/IM), seclusion, and physical restraint for psychiatric patients suspected of or presenting with PMA. The protocol is applicable within the Spanish healthcare system. Implementation of the protocol and the constituent algorithms described here should ensure the best standard of care of patients at risk of PMA. Episodes of PMA could be identified earlier in their clinical course and patients could be managed in the least invasive and coercive manner, ensuring their own safety and that of others around them.ConclusionEstablishing specialized teams in agitation and providing them with continued training on the identification of agitation, patient management and therapeutic alternatives might reduce the burden of PMA for both the patient and the healthcare system.

Surgery in ROP, when is not too late?

SummaryRetinopathy of prematurity (ROP) is the leading cause of preventable blindness in the premature newborn, when there is retinal detachment (RD) in children with ROP, even in limited detachments, the severity and extent of the RD as well as the expedited treatment are key factors to limit the resulting visual disability. The surgical treatment in children with RD due to ROP is aim to limit its extension, preserve anatomy as far as possible and facilitate visual rehabilitation. Advanced stages of ROP are poorly understood, this results in the lack of early detection of RD. Stages 4A and 4B have better prognosis if treated early, in stage 5 often the doubt exists if the anesthetic risk or the time and work necessary for the surgery are worth it since in most cases the anatomical and visual result is bad. We will analyze the types of traction leading to RD, the planning of surgery, the use of pharmacological agents, the recommended time to perform the procedure, autor's recommendations to decide the type of procedure to be performed and the follow‐up. The surgical management of the advanced stages of ROP in an early form may allow in some cases to preserve vision in eyes with retinal detachments in which the macula is still redeemable.

Perioperative Blood Management in Pediatric Spine Surgery.

Blood management strategies are integral to successful outcomes in many types of orthopaedic surgery. These strategies minimize blood loss and transfusion requirements, ultimately decreasing complications, improving outcomes, and potentially eliminating risks associated with allogeneic transfusion. Practices to achieve these goals include preoperative evaluation and optimization of hemoglobin, the use of pharmacologic agents or anesthetic methods, intraoperative techniques to improve hemostasis and cell salvage, and the use of predonated autologous blood. Guidelines can also help manage allogeneic transfusions in the perioperative period. Although the literature on blood management has focused primarily on arthroplasty and adult spine surgery, pediatric spinal fusion for scoliosis involves a large group of patients with a specific set of risk factors for transfusion and distinct perioperative considerations. A thorough understanding of blood management techniques will improve surgical planning, limit transfusion-associated risks, maintain hemostasis, and optimize outcomes in this pediatric population.

Update on Treatment Guideline in Fibromyalgia Syndrome with Focus on Pharmacology.

Fibromyalgia syndrome (FMS) is a chronic condition with unknown aetiology. The pathophysiology of the disease is incompletely understood; despite advances in our knowledge with regards to abnormal central and peripheral pain processing, and hypothalamo–pituitary–adrenal dysfunction, there is no clear specific pathophysiological therapeutic target. The management of this complex condition has thus perplexed the medical community for many years, and several national and international guidelines have aimed to address this complexity. The most recent guidelines from European League Against Rheumatism (EULAR) (2016), Canadian Pain Society (2012), and The Association of the Scientific Medical Societies in Germany (AWMF) (2012) highlight the change in attitudes regarding the overall approach to FMS, but offer varying advice with regards to the use of pharmacological agents. Amitriptyline, Pregabalin and Duloxetine are used most commonly in FMS and though modestly effective, are useful adjunctive treatment to non-pharmaceutical measures.

Management of bronchiolitis in infants: key clinical questions

Abstract Bronchiolitis is the most common lower respiratory tract infection in infants. It is a seasonal illness and remains the leading cause of hospitalisation of infants worldwide. Respiratory syncytial virus (RSV) is responsible for approximately 70% of cases. Infants present with coryzal symptoms progressing to a cough and respiratory distress. A mild pyrexia and reduced feeding are common. Bronchiolitis is a clinical diagnosis and investigations are often of limited value. The management of bronchiolitis remains a contentious issue with a wide variation in practice. Recently here has been a significant shift in favour of minimally invasive, supportive therapy as the cornerstone of management. This typically involves minimal handling, nasopharyngeal suction, oxygen supplementation and optimising hydration. There is little evidence to support the use of pharmacological agents in managing of bronchiolitis. Palivizumab, a monoclonal antibody targeting RSV, can be administered to high risk patients in an attempt to reduce admission rates.

Metrics for glycaemic control - from HbA1c to continuous glucose monitoring.

As intensive treatment to lower levels of HbA1c characteristically results in an increased risk of hypoglycaemia, patients with diabetes mellitus face a life-long optimization problem to reduce average levels of glycaemia and postprandial hyperglycaemia while simultaneously avoiding hypoglycaemia. This optimization can only be achieved in the context of lowering glucose variability. In this Review, I discuss topics that are related to the assessment, quantification and optimal control of glucose fluctuations in diabetes mellitus. I focus on markers of average glycaemia and the utility and/or shortcomings of HbA1c as a 'gold-standard' metric of glycaemic control; the notion that glucose variability is characterized by two principal dimensions, amplitude and time; measures of glucose variability that are based on either self-monitoring of blood glucose data or continuous glucose monitoring (CGM); and the control of average glycaemia and glucose variability through the use of pharmacological agents or closed-loop control systems commonly referred to as the 'artificial pancreas'. I conclude that HbA1c and the various available metrics of glucose variability reflect the management of diabetes mellitus on different timescales, ranging from months (for HbA1c) to minutes (for CGM). Comprehensive assessment of the dynamics of glycaemic fluctuations is therefore crucial for providing accurate and complete information to the patient, physician, automated decision-support or artificial-pancreas system.

An overview of current treatments in heart failure

Heart failure is a disease with a high morbidity and mortality. The European Society of Cardiology (ESC) updated its clinical guidelines in 2016 to reflect the latest evidence base. This article will provide an overview of current treatments in heart failure based on these updated guidelines. It will outline the use of pharmacological agents, including the newest drug available—sacubitril valsartan—the use of non-pharmacological agents, such as cardiac resynchronisation therapy, and the role of patient education and support. For patients with advanced heart failure, recognising the need for an advanced heart failure assessment and recognising the end of life with palliative care provision, will be discussed. The role of the heart failure nurse specialist will be reviewed as a pivotal part of the heart failure specialist team, particularly with respect to patient monitoring and the up-titration of key heart failure treatments.