Frontiers in Pharmacology最新文献

Background: Insomnia disorder is a chronic medical condition estimated to affect 12% of adults. The potential for abuse of hypnotics often contributes to physician reluctance to prescribe medications to treat insomnia as a chronic condition. This study examined the real-world abuse potential of approved and off-label medications used to treat insomnia, employing data from the FDA Adverse Event Reporting System (FAERS) database.

Methods: Data from 1 January 2014 to 31 March 2024 were retrieved. Drugs of interest included Schedule IV drugs (benzodiazepines, Z-drugs, dual orexin receptor antagonists [DORAs]) and non-scheduled drugs (trazodone, doxepin, ramelteon). Relevant reported adverse events denoting drug abuse were identified if they contained an event with any preferred terms from the SMQ Drug abuse, dependence, and withdrawal (MedDRA v26.1), with cases of overdose due to suicide attempts excluded. The reporting odds ratios (ROR) and proportional reporting ratios (PRR) were used as disproportionality measures.

Results: Rates of adverse event cases of abuse, dependence, and withdrawal retrieved were highest for benzodiazepines approved for any indication, followed by benzodiazepines approved for insomnia, trazodone, doxepin, Z-drugs, ramelteon, and DORAs. DORAs were associated with a low ROR value relative to Z-drugs (ROR = 0.150; 95% CI [0.131, 0.171]) and to trazodone (ROR = 0.092; 95% CI [0.081, 0.105]). Similar results were obtained using the PRR. The DORA class had the lowest rates of adverse event denoting drug abuse, even lower than the unscheduled drugs ramelteon and doxepin, which are known not to be prone to abuse or dependence. Furthermore, the DORA class had significantly lower odds of reporting for adverse events denoting drug abuse when compared with zolpidem or the unscheduled medication trazodone.

Conclusion: This study identified significantly fewer reported cases of real-world abuse, misuse, overdose, and other safety risks for DORAs compared with the unscheduled drug trazodone and scheduled Z-drugs. This suggests that categorization of DORAs as Schedule IV drugs may overstate their abuse potential.

Introduction: Acetaminophen, a widely used analgesic and antipyretic, can cause adverse reactions ranging from mild urticaria to severe anaphylaxis. While interindividual differences in pharmacokinetics and genetic polymorphisms are known to affect acetaminophen metabolism, the specific mechanisms underlying hypersensitivity reactions (HSRs) remain unclear.

Methods: We evaluated 28 patients with single-NSAID-induced urticaria/angioedema or anaphylaxis, but no other symptoms after acetaminophen intake. All patients demonstrated selective hypersensitivity to acetaminophen while exhibiting confirmed tolerance to acetylsalicylic acid (ASA). Oral provocation tests were conducted, and NAPQI adducts and acetaminophen metabolites were quantified in serum samples using HPLC coupled with mass spectrometry in these patients and in control individuals.

Results: NAPQI generation occurred early after drug administration, within the timeframe when immediate HSRs occur. NAPQI adducts were 3-fold higher in patients with positive oral provocation compared to patients with negative oral provocation, (P = 0.028), despite lower acetaminophen doses. Detoxified NAPQI metabolites were reduced in HSR individuals, suggesting impaired detoxification. A trend toward higher adduct levels was observed in individuals with GSTM1 null genotypes.

Conclusion: Our findings indicate that NAPQI adduct generation is closely related to acetaminophen HSRs, supporting a mechanistic link between impaired NAPQI detoxification and acetaminophen HSR. Genetic variability in detoxifying enzymes, particularly GSTM1, may modulate individual susceptibility. These findings warrant further investigation into NAPQI adducts as predictive biomarkers for acetaminophen hypersensitivity.

Background: China is characterized by significant regional disparities in economic development levels. Accordingly, both the regional implementation effectiveness of the national centralized drug procurement (NCDP) policy and relevant influencing factors urgently require investigation, with the aim of providing evidence to optimize the policy's implementation.

Methods: The first to fifth batches of NCDP drugs were investigated on the basis of the adjusted standard survey methodology suggested by the World Health Organization/Health Action International. This study has assessed NCDP drug availability across over 900 secondary and tertiary public general hospitals in regions with varying levels of economic development in terms of both the procurement rate and the availability rate.

Results: The availability of these five batches of NCDP drugs in regions with different economic development levels generally followed the pattern that their availability in developed regions is higher than that in moderately developed regions which is also higher than that in less developed regions. A significant difference was observed in the availability of different batches of NCDP drugs (P < 0.05). In developed regions, the average availability rate of each batch was relatively high (from 53.34% to 70.42%), and their procurement rates exceeded 50%. In moderately developed regions, all batches except the fourth exhibited relatively high average availability rates (from 50.08% to 65.14%), and their procurement rates all exceeded 50%. In less developed regions, only two batches (the first batch of "4 + 7" expansion and the second batch) exhibited relatively high average availability rates, and their procurement rates exceeded 50%. The availability of all types of NCDP drugs was also higher in more developed regions.

Conclusion: The implementation of five batches of NCDP drugs has gained initial achievements, but differences persist among regions with varying economic development levels. Accordingly, relevant national departments should optimize the policy implementation mechanism, strengthen the construction of supply chains, and change the inertia of medical behaviour in these regions, aiming to promote the coordinated development of different regions, increase the availability of NCDP drugs and allow people to enjoy policy benefits.

Background: Midazolam and dexmedetomidine are widely used sedatives for mechanically ventilated patients in the intensive care unit (ICU). However, their comparative effectiveness and safety remain debated. This systematic review and meta-analysis aimed to evaluate randomized controlled trials (RCTs) directly comparing these agents.

Methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, The Cochrane Library, Web of Science, and Embase were searched through August 2025. Eligible studies were RCTs comparing midazolam with dexmedetomidine in adult ICU patients requiring invasive mechanical ventilation. Outcomes included mechanical ventilation duration, ICU length of stay, delirium, hemodynamic adverse events, and mortality. Pooled estimates were calculated using fixed- or random-effects models, with subgroup and sensitivity analyses performed to assess robustness.

Results: Fifteen RCTs with diverse international populations were included. Dexmedetomidine significantly reduced mechanical ventilation duration (WMD = -0.96 days, 95% CI: -1.56 to -0.36) and lowered delirium risk (RR = 0.59, 95% CI: 0.52-0.68). It was, however, associated with a higher incidence of bradycardia (RR = 2.05, 95% CI: 1.61-2.62). No significant differences were observed in ICU length of stay (WMD = -0.89 days, 95% CI: -2.41 to 0.62) or all-cause mortality (RR = 0.96, 95% CI: 0.79-1.18). Sensitivity analyses confirmed the stability of pooled results. Subgroup analyses suggested stronger benefits of dexmedetomidine in Asian studies and in smaller trials, while the protective effect against delirium was more pronounced in older patient cohorts.

Conclusion: Dexmedetomidine demonstrated clinical advantages over midazolam by reducing delirium and ventilation duration but carried a greater risk of bradycardia. Sedative choice should balance efficacy with cardiovascular safety.

Introduction: Boehmeria nivea (L.) Gaud. has traditionally been regarded as a medicinal food with applications in various inflammatory disorders. However, its role in chronic obstructive pulmonary disease (COPD) has not yet been clarified.

Methods: In this study, the preventive efficacy of the ethyl acetate fraction of B. nivea (L.) Gaud. leaves (EA-BN) was evaluated in a COPD model established by intratracheal instillation of lipopolysaccharide (LPS; 0.5 mg/kg body weight) and cigarette smoke condensate (CSC; 12.5 mg/kg body weight) in male C57BL/6N mice. The experimental groups received dexamethasone (3 mg/kg) as a positive control or EA-BN at doses of 100 and 200 mg/kg.

Results: EA-BN administration significantly reduced T helper 1 cytokine levels and decreased macrophage and neutrophil counts in bronchoalveolar lavage fluid. Histological analyses revealed that EA-BN mitigated alveolar destruction and inflammatory infiltration, whereas pulmonary function tests demonstrated improvements in the FEV0.1/FVC ratio and lung elastance in the LPS/CSC-induced COPD. Additionally, EA-BN alleviated oxidative stress by promoting the nuclear translocation of Nrf2 and enhancing the expression of its downstream targets, HO-1 and NQO1, leading to a reduction in reactive oxygen species and nitric oxide production. EA-BN downregulated thioredoxin-interacting protein and NLRP3 inflammasome activation, thereby suppressing caspase-1 and IL-1β expression, whereas also attenuating apoptosis by modulating the Bax/Bcl-2/caspase-3 pathway.

Discussion: Collectively, these findings suggest that EA-BN possesses antioxidant, anti-inflammatory, and anti-apoptotic properties, supporting its potential as a preventive agent against COPD.

Natural products, especially those from medicinal plants, have been increasingly attractive to researchers. Wedelolactone (WL) is a natural coumestan that was first isolated from Wedelia Chinensis. The past decades have seen an increase in the pharmacological reports on this compound, which show that WL possesses anti-inflammatory, antiviral, antibacterial, antitumor and anti-osteoporosis activities, as well as protective effects on organ damages. This review integrates the recent progresses available on its pharmacological effects both in vitro and in vivo, and highlights its potential uses in multiple diseases.

Porphyrin-based metal-organic frameworks (MOFs) offer exceptional advantages for cancer therapy, including high photosensitizer loading, tunable nanostructures, and suppression of porphyrin self-quenching. By functionalizing with mitochondria targeting ligands, these platforms deliver reactive oxygen species (ROS) precisely to mitochondria, the oxygen-rich and ROS-sensitive organelle, dramatically enhancing photodynamic therapy (PDT) efficacy. This design paradigm has been successfully extended to sonodynamic therapy (SDT) and radiotherapy/radiodynamic therapy (RT-RDT), where porphyrin-MOFs integrate additional functions such as glutathione depletion, CO/H₂S gas release, or immune activation. Upon ultrasound or X-ray irradiation, these systems synergistically amplify mitochondrial oxidative damage, overcoming hypoxia, antioxidant defenses, and apoptosis resistance. The diversified applications (PDT, SDT and RDT) exemplifies a multimodal strategy that leverages the unique physicochemical properties of porphyrin-MOFs to achieve spatiotemporally controlled, organelle-specific therapy. Looking ahead, the development of intelligent, stimuli-responsive porphyrin-MOF nanoplatforms holds great promise for clinical translation, enabling integrated theranostics and personalized cancer treatment through precise mitochondrial targeting.