European Journal of Clinical Pharmacology最新文献

Purpose: Propranolol, a non-selective beta-blocker characterized by high lipid solubility, is extensively prescribed for cardiovascular and central nervous system disorders. Nevertheless, it is frequently implicated in intentional overdoses due to its central nervous system penetration and membrane-stabilizing properties, often resulting in life-threatening bradycardia, hypotension, seizures, and cardiac arrest. This systematic review aimed to assess the efficacy of the current medical and mechanical interventions employed in the management of propranolol toxicity.

Methods: A comprehensive literature search was conducted using PubMed, EMBASE, CENTRAL, and Google Scholar for studies published between 1965 and March 18, 2025. Search terms included "propranolol toxicity," "glucagon," "high-dose insulin therapy," "lipid emulsion," "calcium," and "extracorporeal life support." Studies were included if they confirmed propranolol toxicity, evaluated at least one therapeutic intervention, and reported the clinical or hemodynamic outcomes. Expert opinions, narrative reviews, and letters to the editor were excluded from the analysis.

Results: A total of 92 studies were included, comprising observational studies, case series, detailed case reports, preclinical animal experiments, and animal control trials. Glucagon emerged as the most frequently utilized pharmacologic agent, followed by high-dose insulin euglycemic therapy (HDIET), intravenous lipid emulsion (ILE), inotropes, and calcium salts. Mechanical interventions such as extracorporeal life support (ECLS), pacing, and hemoperfusion have been reported in severe or refractory cases. The quality of evidence varied, with most studies limited by design heterogeneity, small sample sizes, and a lack of randomized controlled trials.

Conclusion: Multiple interventions, including glucagon, HDIET, ILE, calcium, and ECLS, have demonstrated benefits in managing propranolol toxicity. However, owing to the low level of evidence and wide variability in patient presentations and treatment protocols, no single therapy exhibits universal efficacy. Individualized multimodal treatment remains essential, and high-quality clinical studies are necessary to establish standardized evidence-based protocols.

Background: In recent years, increasing evidence has emerged regarding the use of direct oral anticoagulants (DOACs) for the treatment of splanchnic vein thrombosis (SVT) in non-cirrhotic patients. However, available data are predominantly retrospective, derived from small and heterogeneous cohorts; consequently, the use of DOACs for this indication remains off-label.

Methods: To further evaluate the safety and efficacy of DOACs in this setting, 21 consecutive patients with acute non-cirrhotic SVT were enrolled and treated with DOACs for a minimum of 6 months.

Results: No cases of SVT progression, recurrence, or major bleeding were observed during follow-up. One patient experienced a minor bleeding event.

Conclusions: These findings are consistent with previous reports indicating a favorable safety profile of DOACs, with a low risk of bleeding. However, conclusions regarding efficacy remain uncertain, precluding definitive inferences on their effectiveness in non-cirrhotic SVT. Larger, well-designed prospective studies are required to clarify the true efficacy of DOACs in this clinical setting.

Purpose of review: Chronic kidney disease (CKD) significantly increases the risk of atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia-particularly elevated low-density lipoprotein cholesterol (LDL-C)-being a shared risk factor. While statin-based therapies are effective in early-stage CKD, their benefits in dialysis and kidney transplant patients remain inconclusive. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of lipid metabolism. This review aims to summarize the factors influencing PCSK9 levels in CKD patients and evaluate the safety and efficacy of PCSK9 inhibitors across different stages of CKD.

Recent findings: Multiple factors have been associated with variations in plasma PCSK9 concentrations in CKD, including glycemic status, proteinuria, renal function, dialysis modality, lipid-lowering therapy, and circadian rhythms. PCSK9 inhibitors, such as alirocumab, evolocumab, and inclisiran, effectively reduce LDL-C and ASCVD risk in patients with mild-to-moderate CKD. However, evidence is limited in patients with advanced CKD (stages 4-5, end stage renal disease (ERSD)), particularly those undergoing dialysis. Elevated PCSK9 levels may not independently predict ASCVD risk in CKD populations. Nonetheless, PCSK9 inhibitors provide a well-tolerated and effective lipid-lowering option in early CKD. Large-scale prospective studies are warranted to clarify their role in patients with ESRD.

Background: Hemodynamic instability during colonoscopy sedation remains a significant clinical concern. Esketamine's sympathomimetic properties may protect against these risks while reducing sedative requirements. Hence, we aim to evaluate the efficacy and safety of esketamine in improving intraprocedural sedation during colonoscopy.

Methods: We systematically searched PubMed, Scopus, CENTRAL, and Web of Science until June 2025 for randomized controlled trials. The primary outcome was the incidence of intraprocedural hypotension; secondary outcomes included bradycardia, hypoxemia, and recovery parameters. Dichotomous outcomes were pooled using risk ratios (RR) and continuous outcomes using standardized mean differences (SMD), with heterogeneity assessed via I² statistics.

Prospero id: CRD420251105691.

Results: Five randomized controlled trials comprising 858 patients were included in our analysis. Esketamine significantly reduced the risk of intraprocedural hypotension (RR: 0.34, 95% CI 0.22-0.53; I²=58%) and the incidence of hypoxemia (RR: 0.38, 95% CI 0.19-0.73; I²=0%). A reduction in injection pain was also observed (RR: 0.42, 95% CI 0.19-0.97; I²=80.5%), though this finding showed sensitivity in leave-one-out analysis. No significant differences were found between groups in bradycardia risk (RR: 0.51, 95% CI 0.23-1.14), total propofol requirement (SMD: -0.23, 95% CI -0.50 to 0.04), induction time, or procedure duration. The reduction in hypotension remained robust in sensitivity analyses.

Conclusion: Esketamine significantly enhanced hemodynamic stability and reduced sedative demand during colonoscopy without delaying recovery, supporting its use in high-risk patients.

Purpose: Antibiotics are widely used in the management of bacterial infections However; most antibiotics are not known for DRESS. Our objective is to find out the association of DRESS with available antibiotics using disproportionality analysis.

Methods: Retrospective pharmacovigilance disproportionality analysis based on the FDA Adverse Event Reporting System (FAERS) database from a period of 2004 Q1- 2022 Q3 was conducted using OpenVigil 2.1 tool. Disproportionality measures like Proportional reporting Ratio with associated Chi- square values (PRR ≥ 2 with associated χ2 ≥ 4), ROR with a 95% confidence interval (lower limit of 95% C.I. of ROR is greater than 1), and the number of cases of co-occurrence (n) were used for the identification of novel signals.

Results: A total of 13,918 cases of DRESS were reported, out of which 5,455 cases were found with various classes of antibiotics. The signal of DRESS was identified with a total of 40 antibiotics. Sub groups analysis results have shown variation in the strength of signal based on gender, age groups and geographical locations. The sensitivity analysis results have shown a decrease in the strength of signal after removal of cases of concomitant drugs.

Conclusion: 22 antibiotics were identified which can be associated with DRESS; however, further causality assessment is required to confirm the association.

Background and objectives: Lumbar spinal stenosis (LSS) is a common degenerative condition and a leading cause of pain and disability in older patients. While conservative treatment options like limaprost, a prostaglandin E1 analog, and pregabalin, a neuropathic pain modulator, are increasingly used, their relative efficacy and safety remain unclear. This systematic review aims to evaluate the comparative efficacy of pregabalin and limaprost in managing pain, function, quality of life, and adverse events in LSS.

Methods: A systematic search was conducted following PRISMA guidelines. Searches were performed across PubMed, Embase, Scopus, and Cochrane for studies published between January 2000 and March 2025. Inclusion criteria focused on RCTs and cohort studies evaluating either drug in LSS patients.

Results: Nine studies (6 RCTs, 3 cohort studies) with a total of 860 participants were included. Two head-to-head trials found no significant differences between pregabalin and limaprost in improving pain, disability, or quality of life. Both agents were associated with significant within-group improvements. Pregabalin showed efficacy across outcomes when combined with NSAIDs but was consistently associated with a higher frequency of adverse events, primarily including dizziness and gastrointestinal disturbances, compared to limaprost. Limaprost demonstrated mixed results, with several studies reporting benefits primarily when combined with other agents instead of its monotherapy. Evidence on sleep quality outcomes was limited but suggests potential benefits for both drugs in this patient population.

Conclusion: No agent demonstrated clear superiority in the treatment of LSS, though both pregabalin and limaprost showed significant within-group benefits. Pregabalin's greater side effect profile and cost may support preferential use of limaprost in LSS patients. Nevertheless, due to limited comparative trials and substantial heterogeneity in interventions and outcome measures, further high-quality studies are needed to elucidate this non-inferiority and inform clinical guidelines.