Basic & Clinical Pharmacology & Toxicology

Bupropion is widely used for the treatment of major depressive disorder and for smoking cessation assistance. Unfortunately, there are no practical systems to assist clinicians or poison centers in predicting outcomes based on clinical features. Hence, the purpose of this study was to use a decision tree approach to inform early diagnosis of outcomes secondary to bupropion overdose. This study utilized a dataset from the National Poison Data System, a six-year retrospective cohort study on toxic exposures and patient outcomes...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Deprescribing is an essential component of safe prescribing, especially for people with higher levels of polypharmacy. Identifying individuals prepared to consider medicine changes may facilitate deprescribing-orientated reviews. We aimed to explore the relationship between revised Patient Attitudes Towards Deprescribing (rPATD) scores and medication changes in older people prescribed ≥15 medicines. A secondary analysis of rPATD scores and prescription data from a cluster randomised controlled trial of a GP-delivered, deprescribing-orientated medication review was conducted...

The 57-mer full-length GPR15L(25-81) peptide has been identified as the principal endogenous agonist of the G protein-coupled receptor GPR15. Its main activity resides in the C-terminal 11-mer GPR15L(71-81), which has full efficacy but ~40-fold lower potency than the full-length peptide. Here, we systematically investigated the structure-activity-relationship of GPR15L(71-81) by truncations/extensions, alanine-scanning, and N- and C-terminal capping. The synthesized peptide analogues were tested at GPR15 stably expressed in HEK293A cells using a homogenous time-resolved Förster resonance energy transfer based Gi cAMP functional assay...

VLGR1/ADGRV1 (very large G protein-coupled receptor-1) is the largest adhesion G protein-coupled receptor aGPCRs. Mutations in VLGR1/ADGRV1 are associated with human Usher syndrome, the most common form of deaf-blindness, and also with epilepsy in humans and mice. VLGR1 is expressed almost ubiquitously, but is mainly found in the CNS and in the sensory cells of the eye and inner ear. Little is known about the pathogenesis of the diseases related to VLGR1. We previously identified VLGR1 as a vital component of focal adhesions (FA) serving as a metabotropic mechanoreceptor controls cell spreading and migration...

No abstract text is available yet for this article.

Cyclopeptide mushroom poisoning is responsible for 90%-95% of deaths from macrofungi ingestion. The main objectives of this study are to describe cases of cyclopeptide mushroom poisoning and to determine risk factors that may influence the severity/mortality of poisoned patients. We included all cases of amatoxin toxicity reported to two French Poison Centers from 2013 through 2019. We compared the severity with the Poison Severity Score (PSS) and the outcomes of patients using simple logistic regression and multinomial logistic regression...

The purpose of this study was to examine factors important to older adults who agreed with a deprescribing recommendation given from a General Practitioner (GP) to a hypothetical patient experiencing polypharmacy. We conducted an online, vignette-based, experimental study in the United Kingdom, United States, and Australia with participants ≥65 years. The primary outcome was agreement with a deprescribing recommendation (6-point Likert scale; 1=strongly disagree and 6=strongly agree). We performed a content analysis of the free text reasons provided by participants who agreed with deprescribing (score of 5 or 6)...

Antidote stocking has been described in several studies from many countries to be problematic, and constantly insufficient. During our institution's previous experience with a medication event that resulted from lack of antidote stocking, we initiated a review of all our antidotes and realized the lack of data on utilization in the literature that would help us in planning for our stocks. Therefore, we conducted this retrospective review of antidotes utilized at a large tertiary care hospital over a period of six years...

This study aimed to investigate the effect of intranasal treatment of gold nanoparticles (GNPs) and Curcumin (Cur) on the lipopolysaccharide (LPS)-induced acute pulmonary inflammatory response. A single intraperitoneal injection of LPS (0.5 mg/Kg) was performed, and the animals in the Sham group were injected with 0.9% saline. Treatment was daily intranasally with GNPs (2.5 mg/L), Cur (10 mg/kg) and GNP-Cur started 12 hours after LPS administration and ended on the seventh day. The results show that the treatment performed with GNP-Cur was the most effective to attenuate the action of pro-inflammatory cytokines, and a lower leukocyte count in the bronchoalveolar lavage, in addition to positively regulating anti-inflammatory cytokines in relation to other groups...

Chemotherapy-induced mucositis, characterised by diarrhoea and villous atrophy, is a severe side effect contributing to reduced quality of life and premature death in cancer patients treated with cytostatics. Despite its high incidence, there is no effective supportive therapy available. The main objective of this study was to determine if the anti-inflammatory drugs anakinra and/or dexamethasone - which have different mechanism-of-action - might be used to effectively treat idarubicin-induced mucositis in rats...

This study explores the role of steroid administration in identifying distressed or even mentally disordered cancer patients (so-called case finding). Charts of 12,298 cancer patients (4499 treated with prednisone equivalents) were analyzed descriptively. A subset of10,945 was further explored via latent class analysis (LCA). LCA avoids confounding by indication because it subgroups patients without prior preconceptions based on homogeneous expression of traits (i.e. the variables examined). Latent class analysis identified four subgroups: Two subgroups with high dosages of prednisone equivalent (≥80mg/day on average over all treatment days) and two with low dosages...

Opioids change gut motility and opium tincture has been used for treatment of chronic diarrhoea for centuries. However, the effects have never been documented in controlled trials. We aimed to investigate the effects of opium tincture on gastrointestinal transit and motility, frequency of bowel movements, stool consistency, gastrointestinal symptoms, and sedation. Twenty healthy subjects were included in this randomized controlled trial. Opium tincture or placebo were each applied for nine days. Gastrointestinal transit and motility were investigated with the 3D-transit system...

AIMS: To investigate prescribing and therapeutic drug monitoring (TDM) practices for vancomycin in pediatrics at the Jordan University Hospital and to determine the impact of inaccuracies in TDM data on dosing decisions. METHODS: Patterns of vancomycin prescriptions, appropriateness of vancomycin dosing, duration, TDM, and the accuracy of the recorded dosing/sampling times were determined prospectively based on prespecified criteria. Finally, Monte-Carlo simulations were undertaken using the mrgsolve-package in R to assess the effect of inaccuracies in recording dosing/sampling times on subsequent dose adjustments...

Intracerebral hemorrhage (ICH) is a catastrophic subtype of stroke with severe morbidity and mortality. However, little progress has been made in the subsequent secondary injury. Artesunate, a water-soluble semi-synthetic derivative of artemisinin, exhibits remarkable pharmacological effects on anti-neuroinflammation. However, the effects of artesunate on ICH remain unknown. In the present study, hemoglobin (Hb) treatment in BV2 cell and collagenase type IV intracerebroventricular injection in Sprague-Dawley rats were used to establish in vitro and in vivo ICH models, respectively...

Due to a narrow therapeutic index, prolonged lithium treatment and overdose may result in neurotoxicity. Neurotoxicity is deemed reversible with lithium clearance. However, echoing the report of syndrome of irreversible lithium-effectuated neurotoxicity (SILENT) in rare severe poisonings, lithium-induced histopathological brain injuries including extensive neuronal vacuolization, spongiosis and ageing-like neurodegenerative changes were described in the rat following acute toxic and pharmacological exposure...

In Denmark, reporting of safety incidents to the nationwide Danish Patient Safety Database (DPSD) is mandatory. Medication incident reports constitute the largest category of safety reports. We aimed to provide numbers and characteristics of medication incidents and MEs reported to DPSD focusing on medication, their severity and the trends therein. This is a cross-sectional study of medication incident reports for individuals ≥18, submitted to DPSD in 2014-2018. We performed analyses on the (1) medication incident and (2) ME levels...

BACKGROUND: Deprescribing (reduction or cessation) of prescribed opioids can be challenging for both patients and healthcare professionals. OBJECTIVE: To synthesize and evaluate evidence from systematic reviews examining the effectiveness and outcomes of patient-targeted opioid deprescribing interventions for all types of pain. METHODS: Systematic searches were conducted in five databases with results screened against predetermined inclusion/exclusion criteria...

Atrial arrhythmias are a hallmark of heart diseases. The antiarrhythmic drug ranolazine with multichannel blocker properties is a promising agent to treat atrial arrhythmias. We therefore used the rat model of monocrotaline-induced pulmonary-hypertension to assess whether ranolazine can reduce the incidence of ex vivo atrial arrhythmias in isolated right atrium. Four-week-old Wistar rats were injected with 50 mg/kg of monocrotaline, and isolated right atrium function was studied 14 days later. The heart developed right atrium and right ventricular hypertrophy, and the ECG showed an increased P wave duration and QT interval, which are markers of the disease...