Current drug safety最新文献

Introduction: Postoperative nausea and vomiting (PONV) remain among the most frequent and distressing complications following surgery, often hindering patient recovery and comfort. Penehyclidine, an anticholinergic agent, has been explored as a potential treatment for PONV, yet its safety and efficacy are still under investigation. This systematic review and metaanalysis aim to synthesize current evidence on the effectiveness and safety of penehyclidine in preventing and managing PONV.

Methods: A comprehensive search was performed across several major databases, including PubMed, Scopus, Web of Science, and the Cochrane Library, to identify randomized controlled trials evaluating penehyclidine's efficacy in PONV management. Relevant data were extracted from eligible studies, and outcomes of interest were analyzed. A meta-analysis using a randomeffects model was conducted with RevMan software.

Results: Meta-analysis revealed that penehyclidine significantly reduced the incidence of PONV at both 24 hours (RR = 0.61, 95% CI [0.48-0.82]; p = 0.001) and 48 hours postoperatively (RR = 0.69, 95% CI [0.55-0.86]; p = 0.0009). It also significantly lowered the requirement for rescue antiemetics (RR = 0.34, 95% CI [0.19-0.61]; p = 0.0003). Additionally, patients receiving penehyclidine experienced a greater likelihood of complete symptom relief (RR = 1.37, 95% CI [1.10-1.72]; p = 0.005) and a reduced incidence of severe PONV (RR = 0.36, 95% CI [0.22- 0.60]; p < 0.0001). However, there were no significant differences observed in postoperative analgesic use (RR = 0.99, 95% CI [0.71-1.36]; p = 0.93) or length of stay in the post-anesthesia care unit (PACU) (MD = 0.14 minutes, 95% CI [-0.95, 1.23]; p = 0.81). Notably, penehyclidine was associated with an increased risk of dry mouth (RR = 2.68, 95% CI [2.10-3.43]; p < 0.00001), although other adverse effects-including headache, dizziness, fever, and urinary retention- showed no significant differences between groups.

Conclusion: Penehyclidine demonstrates significant benefits in reducing both the incidence and severity of PONV, along with minimizing the need for additional antiemetic therapy. Its antiemetic effect extends up to 48 hours postoperatively, although this benefit is tempered by a higher likelihood of dry mouth. Importantly, its use does not influence postoperative analgesic consumption or PACU stay duration, supporting its specific utility in PONV management with a manageable safety profile.

Introduction: Sertraline, an SSRI, is widely prescribed for depression and other psychiatric disorders. Although generally well-tolerated, SSRIs can rarely cause bleeding complications due to their effect on platelet aggregation. This case highlights a rare but clinically significant presentation of sertraline-induced ecchymosis in the absence of predisposing factors, contributing to the limited literature on SSRI-associated bleeding events.

Case presentation: A 34-year-old woman presented with large ecchymotic lesions on both arms three weeks after initiating sertraline therapy. She had no history of trauma, bleeding disorders, or concurrent medications. Laboratory evaluations, including coagulation studies and platelet count, were within normal limits. Symptoms resolved after discontinuing sertraline. Causality assessment using the Naranjo adverse drug reaction scale suggested a probable link between sertraline and ecchymosis.

Conclusion: This case underscores the importance of recognizing sertraline as a potential cause of unexplained bruising. Clinicians should maintain a high index of suspicion for rare SSRIinduced bleeding events to ensure timely diagnosis and management.

Introduction: Liposomal amphotericin B is the treatment of choice for visceral leishmaniasis (VL), but its potential adverse effects, including hematologic and neurologic complications, remain a subject of concern. Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe hyperinflammatory syndrome that can occur in VL, and the development of intracerebral hemorrhage (ICH) during treatment adds a critical dimension to patient management. While ICH is an uncommon complication, its possible association with liposomal amphotericin B warrants further exploration.

Case Study: This report discusses a middle-aged man who presented with a 4-month history of recurrent fever. He also reported progressive breathlessness, a sensation of heaviness in the left abdomen, and pedal edema over the past 4 weeks. Additionally, he experienced black discoloration of urine and stool for 2 weeks. Physical examination revealed massive splenomegaly, melena, hematuria, and pancytopenia. Bone marrow aspiration confirmed hemophagocytosis, and the recombinant kinesin antigen-39 (rk39) test for VL was positive. An H-score of 234 indicated a 98-99% probability of HLH. The patient was initiated on treatment with a single dose of liposomal amphotericin B. However, on the fourth day of therapy, he developed a sudden onset of headache followed by altered sensorium. Neuroimaging revealed ICH with surrounding edema and intraventricular extension, causing a significant mass effect. Given the temporal association with treatment initiation, liposomal amphotericin B-induced ICH was considered a potential etiology. He was managed conservatively with three units of single-donor platelets and showed gradual neurological improvement without further invasive intervention. He was eventually discharged in a hemodynamically stable condition.

Conclusion: This case describes the potential risk of ICH as an adverse or trigger effect of liposomal amphotericin B in the setting of VL and HLH. Clinicians should remain vigilant for neurological complications during treatment, emphasizing the importance of close monitoring and individualized therapeutic decisions to optimize patient outcomes.

Introduction: Antimicrobial resistance (AMR) is a pressing global health issue exacerbated by the overuse of antibiotics during the COVID-19 pandemic. Despite WHO guidelines against antibiotics for mild-to-moderate COVID-19 cases without bacterial co-infection, significant misuse has been reported globally. This study aimed to evaluate antibiotic consumption during the COVID-19 pandemic at a hospital in North Macedonia and to analyze adherence to WHO guidelines, with a focus on antimicrobial stewardship, using the ATC and WHO AWaRe classification systems.

Objective: To analyze antibiotic utilization trends from January 2020 to December 2021 and assess adherence to WHO guidelines, focusing on the potential impact on AMR.

Method: This retrospective observational study measured antibiotic consumption in defined daily doses (DDD) per 100 occupied bed-days (DDD/100 OBD) using ATC and WHO AWaRe classifications. Data were obtained only from ICU inpatients treated at the Clinical Hospital in Shtip, North Macedonia. Trends in annual consumption were analyzed, including rate-of-change calculations for individual antibiotics between 2020 and 2021.

Result: Total antibiotic consumption decreased from 2902.6 DDD/100 OBD in 2020 to 2286.5 DDD/100 OBD in 2021. A third-generation cephalosporin, ceftriaxone, was the most consumed antibiotic, accounting for 57.62% of total consumption in 2020 and 48.55% in 2021. Tetracycline use slightly increased from 13.88% in 2020 to 15.83% in 2021. Fluoroquinolone use decreased significantly from 15.22% in 2020 to 6.5% in 2021. Carbapenem consumption rose sharply from 1.7% in 2020 to 14.37% in 2021, while azithromycin use declined threefold. Antibiotics in the Access group accounted for less than 20% of total usage, while those in the Watch group predominated.

Discussion: The study highlights a continued reliance on broad-spectrum antibiotics during the pandemic, diverging from WHO recommendations emphasizing Access to antibiotics. These trends suggest inadequate implementation of antimicrobial stewardship practices and raise concerns about their long-term impact on AMR. Limitations include the retrospective, single-center design, which may limit the generalizability of the findings.

Conclusion: The findings underscore the high dependency on Watch category antibiotics and a limited focus on Access antibiotics, contrary to WHO recommendations. This highlights the urgent need for robust antimicrobial stewardship programs to control inappropriate antibiotic use and combat AMR.

Introduction: Clopidogrel is a widely used agent in the management of cardiovascular disease. However, there have been reports of liver injury associated with its use, some of which have resulted in death. The atypical presentation of this liver injury has often led to delayed diagnosis and inappropriate treatment. We conducted a systematic review of reported cases to summarize the clinical characteristics, diagnostic approaches, and recovery durations associated with clopidogrel-induced liver injury.

Method: Electronic databases, including MEDLINE, OVID, and EMBASE, were used to identify eligible studies from inception to December 2024. Eligible cases were required to have a clear diagnosis of clopidogrel-induced liver injury. Descriptive analysis and Kaplan-Meier analysis were used to explore the clinical features and survival durations.

Results: Our systematic review included 29 eligible studies, comprising 29 cases of hepatic abscess with a mean age of 67 years (58% male). Patients presented with abdominal pain in only 24% of cases, fever in 17%, but jaundice in 55%. The median recovery time was 25 days after the final diagnosis. A hepatocellular pattern was reported in 37% of cases. Diagnostic criteria were proposed and summarized based on these findings.

Conclusion: Clinicians should be aware of clopidogrel-induced liver injury, as patients can present with a wide range of symptoms. Implementing our proposed diagnostic criteria is recommended to facilitate prompt diagnosis and treatment of clopidogrel-induced liver injury.

The drug approval and review process plays a crucial role in the pharmaceutical industry, aiming to ensure that newly marketed drugs are safe, effective, and of high quality. Regulatory authorities overseeing this process, tailored to geographically distinct needs, include the U.S. FDA, EMA, Japan's Pharmaceuticals and Medical Devices Agency (PMDA), China's National Medical Products Administration (NMPA), and India's Central Drugs Standard Control Organization (CDSCO). This analysis offers insight into the various drug approval processes employed by these authorities and examines the International Council for Harmonisation's ongoing efforts to establish a global consensus on drug regulation standards. It also compares regulatory pathways and highlights current harmonization initiatives. The focus is on analyzing operational aspects of drug regulation and identifying challenges arising from these regulations. The ultimate goal is to present a clear understanding of the intricacies and dynamics of the global drug approval process. Regulating the drug approval process is essential to ensure that new drugs are safe for public consumption, as the introduction of a new drug often faces numerous hurdles beyond safety and efficacy. The challenges highlighted include variations in regulations between authorities, the complexity of modern therapeutics, and the balance between safety and speed. This paper provides an overview of innovations in drug development, their impact on regulatory pathways, ongoing harmonization efforts, and potential obstacles that may arise during the regulatory process.

A transdermal drug delivery system is a convenient drug delivery system where the drug enters the systemic circulation through the protective barrier, i.e., skin. Ethosomes are the ethanolic phospholipid vesicles, which are mainly used for transdermal delivery of medicines. They are nano-vesicular carriers for the topical application of the drugs. The major components of ethosomes are phospholipids, ethanol at relatively high concentrations (up to 50%), and water. The vesicles' composition and structure enhance their ability to entrap molecules with numerous physicochemical characteristics and bring them to the skin's deep layers. Because of their enhanced skin penetration, improved drug delivery, and higher drug entrapment efficiency, ethosomes have become more significant in the field of research. Skin acts as a major target and main barrier for topical or transdermal drug delivery and hence several approaches have been developed to weaken this skin barrier. Vesicular systems like ethosomes are the key approaches to increasing the skin penetration of medicines and various cosmetic components. Ethanol has been added to vesicular systems to create elastic nanovesicles because it is an effective penetration enhancer. For stability and simplicity of use, ethosomal dispersions are added to gels, patches, and creams. This review focuses on research using ethosomal formulations containing natural active compounds for the treatment of skin problems that has been done in vitro, in vivo in animal models, and on people in clinical investigations. Ethosomal systems have been shown to effectively control a variety of skin conditions, including bacterial and fungal infections, inflammation, acne vulgaris, arthritis, skin cancer, etc. Furthermore, ethosomes loaded with various naturally occurring components for cosmetic applications are also reported. The conception of new dermal therapies was made possible by the effective treatments, their good safety profile, and their lack of toxicity or irritation.

Acute kidney injury (AKI) is a severe and life-threatening complication of drug therapy, a significant risk to patient well-being, with high morbidity and death rates. An increasing proportion of AKI cases are mainly caused due to drug-induced nephrotoxicity; despite its prevalence, the exact study of causative drugs is still unclear. AKI is often caused by kidney damage, reducing the kidneys' ability to detoxify, eventually leading to nephrotoxicity. Drug-induced nephrotoxicity often happens through various mechanisms such as crystal nephropathy, oxidative stress, reduced flow to the kidneys, damage to kidney cells, and thrombotic microangiopathy. Epidemiology of drug-induced nephrotoxicity focuses on how prevalent it is and the factors that increase the nephrotoxicity. Specific biomarkers have been found to assess nephrotoxicity for early and accurate diagnosis of kidney damage. This review focuses on explaining drug-induced nephrotoxicity mechanisms for commonly used agents such as non-steroidal anti-inflammatory drugs, immunosuppressants, antibiotics, anticancer agents, and antifungals. It also covers specific biomarkers and respective treatment approaches. Additionally, protective agents and their mechanisms in preventing nephrotoxicity are also analyzed, including their antioxidant and anti-inflammatory potential and other drug-based interventions. This review discusses various therapeutic studies using experimental models, offering invaluable insights into the cellular processes and pathways involved in developing prevention strategies. By advancing our understanding of the mechanisms behind drug-induced nephrotoxicity, it is aimed to improve patient care and reduce health-related complications.

Mitochondrial dysfunction plays a central role in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Targeted drug delivery to mitochondria represents a promising therapeutic strategy to mitigate neuronal degeneration and preserve mitochondrial function in these devastating conditions. This review provides a comprehensive overview of recent advances in targeted drug delivery solutions for mitochondrial dysfunction in neurodegenerative disorders. The mechanisms underlying mitochondrial dysfunction in AD, PD, HD, and ALS are explored, highlighting the specific challenges and opportunities for therapeutic intervention. Emerging drug delivery technologies are discussed, including mitochondriaresponsive systems, nanoparticles, peptides, and viral vectors, designed to deliver therapeutic agents directly to mitochondria along with suitable case studies. Furthermore, preclinical and clinical studies evaluating the efficacy and safety of mitochondria-targeted therapeutics are reviewed, and future directions and challenges in the field are outlined. By elucidating the intersection of mitochondrial biology and drug delivery, this review aims to inspire further research and innovation toward effective treatments for neurodegenerative diseases.