Intranasal drug delivery is noninvasive, rapid-acting, and well suited to self-administration, yet the real-world performance of nasal sprays depends on the interaction among formulation, device mechanics, nasal anatomy, and user technique rather than on the active ingredient alone. This narrative review examines how aerosol science, regional targeting, and human factors jointly shape intranasal performance, using GentleMist Technology™ as a representative example of emerging device-centered development. Computational fluid dynamics (CFD) and anatomically informed in vitro models indicate that device geometry, plume characteristics, and administration angle can significantly alter where a dose is deposited, while human factors research identifies priming, positioning, and angulation as key determinants of successful over-the-counter (OTC) use. We summarize early feasibility data suggesting that angle-optimized administration may increase posterior nasopharyngeal delivery and that essential tasks are feasible for lay users, with priming emerging as a specific usability vulnerability. We also review preliminary clinical evidence on a chlorpheniramine maleate (CPM)-based intranasal formulation in allergic rhinitis and viral upper respiratory illness. Although the strongest device-specific findings remain preliminary and require independent replication, they support an emerging shift from a formulation-centered model toward an integrated device-formulation-user paradigm.

Many drugs that block voltage-gated K+ channels encoded by the human ether-à-go-go-related gene (hERG) can cause long QT syndrome and life-threatening cardiac arrhythmias, yet the molecular mechanisms that determine this risk remain unclear. A process that may counteract arrhythmogenic hERG block, termed facilitation, is common to many clinically approved hERG blockers, including nifekalant, amiodarone, promethazine, imipramine, nortriptyline, haloperidol, verapamil, carvedilol, metoprolol, propranolol, quinidine, fluoxetine, and chlorpheniramine. Facilitation is an increase in hERG current, under certain conditions, due to these blockers. Here, we propose that an agonism-while-blocking mechanism underpins facilitation. We focus on nifekalant, a class III antiarrhythmic drug and exemplar hERG blocker that induces facilitation. We tested the hypothesis that nifekalant opens hERG channel gates while blocking, and that unblocking of these open-yet-blocked channels results in supranormal hERG current. We developed rate-theory kinetic models to identify features of agonism-while-blocking that produce facilitation. We generated atomistic models that predict that nifekalant blocks the hERG conduction path while modulating the intracellular conduction gate. Voltage-clamp measurements revealed that agonism-while-blocking can result in nifekalant block and facilitation. We speculate that this agonism-while-blocking mechanism contributes to the relative safety of hERG blockers that induce facilitation.

Routine urine toxicology screening may be misleading when adolescents present with acute psychotic symptoms and systemic toxicity after exposure to drugs not included in the screening panel. We report a 17-year-old girl with no known psychiatric or neurologic illness who developed agitation, persecutory delusions, fever, diaphoresis, tachycardia, limb rigidity, and a brief generalized tonic-like episode after suspected repeated nonprescribed pregabalin misuse and misuse of an amantadine-containing over-the-counter cold preparation. Collateral history and medication packaging retrospectively suggested 1200 mg pregabalin per episode with six tablets of the cold preparation per episode, corresponding to estimates of 600 mg amantadine and 1500 mg acetaminophen. Serum or urine concentrations of pregabalin and amantadine were not measured, and the serum acetaminophen concentration or international normalized ratio was not obtained. A limited qualitative urine toxicology screen was negative, but the panel did not include pregabalin, amantadine, acetaminophen, caffeine, or chlorpheniramine. Creatine kinase increased from 9590 to 13,840 U/L. Serum myoglobin exceeded the assay upper limit (>2700 ng/mL) and urinalysis supported myoglobinuria. Renal function remained normal. Troponin I remained normal despite creatine kinase-MB elevation, and cardiac assessment did not support primary myocardial necrosis. Neuroimaging and electroencephalography detected no explanatory abnormality. The working diagnosis was probable mixed-medication intoxication with acute delirium, psychotic symptoms, multifactorial rhabdomyolysis, and spontaneous pneumomediastinum with a small pneumothorax. Treatment consisted of drug withdrawal, hydration, cooling, benzodiazepine-based sedation, short-term antipsychotic treatment for dangerous agitation, and conservative pulmonary observation. Creatine kinase decreased to 495 U/L by day 15. This case highlights the need for collateral medication histories and expanded toxicological testing when routine screening is negative.

First-generation H1 antihistamines have central nervous system penetration and anticholinergic activity, with potential side effects including sedation, cognitive impairment, and anterograde amnesia. First-generation antihistamines pose risks in driving under the influence of drugs (DUID) and drug-facilitated crimes (DFC) forensic casework. A liquid chromatography-tandem mass spectrometry method was developed and validated for five first-generation H1 antihistamines: chlorpheniramine, diphenhydramine, doxylamine, hydroxyzine, and promethazine. The calibration range was 1-200 ng/mL with a 1/x linear calibration model for quantitative compounds, and the limit of detection was determined to be 0.5 ng/mL for all compounds. Bias and precision were acceptable, with minor but acceptable suppression observed at low and high concentrations. No exogenous or endogenous interferences were observed. Carryover was not detected after a 400 ng/mL sample. Processed samples were determined to be stable 24 h after initial injection when stored in the refrigerated multi-sampler. Authentic forensic specimens from DUID and DFC investigations showed a wide range of concentrations for diphenhydramine. Selected case reports are presented to demonstrate the applicability of the method. The high percentage of polysubstance cases, range of concentrations, and delayed sample collection in DFC cases underscore the importance of a sensitive and reproducible method for these first-generation antihistamines, especially in human-performance casework.

Prabchompoothaweep (PCT) is an anti-allergic remedy on the Thailand National List of Essential Medicines, traditionally used to relieve common colds and allergic reactions in Thai traditional medicine (TTM). However, the anti-allergic activity of PCT and its plant ingredients had not been characterized. We evaluated the acute and chronic oral toxicity of PCT ethanolic extract in rats and assessed its in vitro and in vivo anti-allergic activities. Activity in vitro was measured as inhibition of antigen-induced β-hexosaminidase release in RBL-2H3 cells and in vivo using an ovalbumin (OVA)-induced allergic rhinitis mouse model. The extract produced no mortality or signs of toxicity in either study. Several plant ingredients and the PCT extract inhibited β-hexosaminidase release more effectively than chlorpheniramine. In OVA-induced mice, PCT (75, 150, and 300 mg/kg) did not significantly lower OVA-specific serum IgE or IgG2a (OVA-specific IgG1 was likewise not reduced); however, it reduced inflammatory cell infiltration, goblet cell hyperplasia and mast cell numbers in the nasal mucosa and downregulated the T helper 2 (Th2) cytokines IL-5 and IL-13. These findings support the traditional anti-allergic use of the PCT remedy.

Recently, abuse and fatal overdoses of over-the-counter (OTC) medications have become serious social and health issues worldwide. However, many drug components in OTC medications that are abused have different chemical structures from those assessed by commercially available rapid drug test kits. In this research, we focused on using dried blood spot (DBS) samples to develop a simple and accurate method for forensic toxicological analysis of drugs of interest in deaths by poisoning. We combined the DBS method with liquid chromatography coupled with electrospray ionization-tandem mass spectrometry to quantify eight OTC drug components (apronal, caffeine, chlorpheniramine, dextromethorphan, diphenhydramine, diprophylline, noscapine, and promethazine). The linearities of the calibration curves were good in the concentration range of 0.1-2.0 μg/mL. The method achieved repeatable and accurate quantification of the eight target drugs with intra- and inter-assay coefficients of variation of below 13.0% and 12.6%, respectively. Comparison with our general practice method showed good positive correlations at the quantifiable concentrations of all drugs. Furthermore, when applied to an actual case, it was possible to diagnose death by drug poisoning, confirming the usefulness of this method.

Enantiomeric separation is essential in pharmaceutical analysis because enantiomers can differ markedly in pharmacological activity, metabolism, and safety. HPLC using chiral mobile-phase additives (CMPAs), particularly cyclodextrin-based selectors, provides a flexible and cost-effective alternative to dedicated chiral stationary phases. However, conventional cyclodextrin CMPA systems are often limited by insufficient stereodiscrimination under aqueous-organic mobile-phase conditions, where solvation and weak noncovalent interactions can restrict chiral recognition. This study explores the potential of deep eutectic solvents (DESs) as auxiliary mobile-phase modifiers for enhancing enantioseparation in β-cyclodextrin polymer-based HPLC chiral mobile phase analysis.

Amivantamab, a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor, has shown clinical efficacy in patients with EGFR-mutated non-small cell lung cancer. Although infusion-related reactions (IRRs) are common adverse events associated with this drug, cardiac events such as bradycardia have rarely been reported. We report the case of a 53-year-old Japanese man with advanced EGFR exon 19-deleted lung adenocarcinoma who was treated with amivantamab plus lazertinib as eighth-line therapy. On the first day, he experienced dyspnea, chills, and headache 30 min after amivantamab administration, so the infusion flow was reduced to 25 mL/h. After the symptoms resolved, the flow rate was set to 50 mL/h. On the second day, 2 h after initiating amivantamab infusion (700 mg) at 50 mL/h, his heart rate decreased to <50 beats per minute (bpm) and subsequently to <40 bpm. His blood pressure remained stable and he had no symptoms. The infusion was interrupted and intravenous methylprednisolone, chlorpheniramine, and atropine were administered. Bradycardia persisted for approximately 24 h but gradually resolved. On rechallenge with amivantamab 10 days later, bradycardia did not recur, suggesting that bradycardia is an IRR. Clinicians should be aware of this potential reaction and closely monitor cardiac rhythm during and after amivantamab infusion.

The increasing incidence of jellyfish stings from expanding global marine activities necessitates painless therapeutic strategies with real-time treatment assessment capabilities. Here, we present a bioinspired core-shell photonic crystal microneedle (PCMN) patch that addresses this need through dual functionality of both therapeutic delivery and optically transduced monitoring. This device is fabricated by coating hyaluronic acid (HA) shells onto non-close-packed PCMN cores, which are functionalized with chlorpheniramine, while the HA shells incorporate lidocaine as a pain management payload. Upon skin insertion, the patch achieves distinct release profiles of lidocaine (from the shell) and chlorpheniramine (from the core), which are consistent with a structure-dependent release mechanism, addressing the distinct temporal requirements of jellyfish envenomation. Critically, this drug release process is accompanied by measurable shifts in the reflection spectrum, enabling real-time and quantifiable optical monitoring of the release process. The quantitative assessment of drug release can be achieved through the position of the reflection peak in an in vitro agarose-phantom model, allowing direct calibration of treatment progress with simple and portable devices. In a murine model of jellyfish sting envenomation, the PCMN@HA platform demonstrated partially attenuated systemic envenomation within 7 h. This work establishes a theranostic platform that integrates a biomimetic device design with optical signal readout, with potential applications extending to other dermatological conditions requiring temporally controlled pharmacotherapy.