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Focused on the assessment of the diphenhydramine hydrochloride (DPH) capabilities as an alternative to conventional and harmful industrial corrosion inhibitors, electrochemical techniques were employed. The optimum concentration of 1000 ppm was determined by molecular simulation and validated through electrochemical experiments. The results acquired from the electrochemical impedance spectroscopy (EIS) study showed that DPH at a concentration of 1000 ppm has a corrosion efficiency of 91.43% after 6 h immersion. The DPH molecules' orientation on the surface was assessed based on EIS predicting horizontal adsorption on the surface. Molecular simulations were done to explore the adsorption mechanism of DPH. The DPH molecules' orientation on the surface was also assessed based on computational studies confirming the horizontal adsorption predicted by EIS. [ABSTRACT FROM AUTHOR]

The surface properties of mixtures of a nonionic surfactant Tween 80 (Tw 80) and a cationic drug, diphenhydramine HCl (DPH) have been investigated. This was done by calculating the surface excess concentration (Γmax), minimum molecular area (Amin), surface pressure at the CMC (ᴨcmc), Gibbs Free Energy of adsorption (ΔG°ads), Gibbs free energy of micellization (ΔG°m), the standard enthalpy of micellization (ΔH°m), and the standard entropy of micellization (ΔS°m). The calculation was performed using the surface tension in the temperature range of 293-323 K with the variation of surfactant concentration to determine the critical micelle concentration (cmc) of the system studied. The variation of cmc values of drug concentration (DPH) with temperature was used to calculate the parameters above. The results indicate that the cmc values of Tw 80 increased when the (DPH) was added and when the temperature increased at the whole temperature studied. The results obtained for interfacial properties show that Γmax decreases with the addition of DPH and decreases with DPH concentration increase from 10-5 to 10-4M and decreases with temperature increases. The results of thermodynamic properties indicate that the micellization and adsorption at the interface are spontaneous and the ΔG̊ads are more negative than ΔG̊m at all temperatures. [ABSTRACT FROM AUTHOR]

The US Food and Drug Administration released a warning related to potential adverse effects related to intentional misuse or abuse ingestions of diphenhydramine in September 2020. We sought to evaluate adolescent-aged (13–19 y) diphenhydramine ingestions reported to US poison control centers to characterize these exposures, adverse effects, outcomes, and trends in outcomes and reasons for ingestion. The US National Poison Database System was queried for all exposures to diphenhydramine between January 1, 2007 and December 31, 2020. 47,644 ingestions were included for analysis. An increase in the number of ingestions, percentage of cases due to an intentional reason for ingestion and suspected suicide was observed. More serious outcomes, cardiac complications, seizures, and deaths were more common following intentional ingestions and specifically suspected suicide over misuse or abuse. Adolescent ingestions of diphenhydramine increased between 2007 and 2020. More serious outcomes, intentional reasons, and suspected suicide also increased over the study interval. Suspected suicide was associated with cardiac complications, seizures, coma, and death at higher rates than misuse or abuse. While misuse and abuse remain a concern, public health interventions focusing on the risk that diphenhydramine pose as an agent of suicide attempt may be of higher impact. [ABSTRACT FROM AUTHOR]

This is a case report of a 55-year-old woman with a past medical history of hypertension who presented to the emergency department with upper lip and cheek swelling isolated to the right side of her face. She was on lisinopril for several years and had never had an episode of swelling in the past. Her vital signs were stable. However, on reassessment, the patient's right sided swelling progressed to the entire upper lip and she complained of swelling in her submandibular space. Although no swelling was appreciated to the submandibular space on physical exam, and the patient still did not have any signs or symptoms of respiratory distress, the decision was made to use a fiberoptic laryngoscope to evaluate her airway. Fiberoptic laryngoscope showed noticeable laryngeal edema which did not improve after treatment, and the patient was admitted to the medical intensive care unit for close airway observation. This case highlights the use of fiberoptic laryngoscope by emergency physicians in the evaluation of patients with relatively benign appearing angioedema. Topics: ACE-I, angioedema, fiberoptic laryngoscope, laryngeal edema, tranexamic acid. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is an autoimmune disease with a strong neuroinflammatory component that contributes to severe demyelination, neurodegeneration and lesions formation in white and grey matter of the spinal cord and brain. Increasing attention is being paid to the signaling of the biogenic amine histamine in the context of several pathological conditions. In multiple sclerosis, histamine regulates the differentiation of oligodendrocyte precursors, reduces demyelination, and improves the remyelination process. However, the concomitant activation of histamine H1–H4 receptors can sustain either damaging or favorable effects, depending on the specifically activated receptor subtype/s, the timing of receptor engagement, and the central versus peripheral target district. Conventional drug development has failed so far to identify curative drugs for multiple sclerosis, thus causing a severe delay in therapeutic options available to patients. In this perspective, drug repurposing offers an exciting and complementary alternative for rapidly approving some medicines already approved for other indications. In the present work, we have adopted a new network-medicine-based algorithm for drug repurposing called SAveRUNNER, for quantifying the interplay between multiple sclerosis-associated genes and drug targets in the human interactome. We have identified new histamine drug-disease associations and predicted off-label novel use of the histaminergic drugs amodiaquine, rupatadine, and diphenhydramine among others, for multiple sclerosis. Our work suggests that selected histamine-related molecules might get to the root causes of multiple sclerosis and emerge as new potential therapeutic strategies for the disease. [ABSTRACT FROM AUTHOR]

Plasma and erythrocyte cholinesterase (ChE) activities of male farm workers exposed to pesticides during their routine work were lower than those of unexposed control subjects by 14 and 4%, respectively. Diphenhydramine and Carbaryl inhibited plasma and erythrocyte ChE activities in vitro in pesticide-exposed and unexposed subjects. The percentages of in vitro ChE inhibition induced by carbaryl in the plasma and erythrocytes of unexposed controls ranged between 47-85% and 19-47%, respectively, whereas they were 35-60% and 3-12% in the pesticide-exposed group, respectively. In vitro pretreatment of plasma and erythrocyte ChE with diphenhydramine (20 µM) significantly reduced the inhibitory effect of carbaryl (10 µM) on them by 18% and 10%, respectively. In conclusion, subjects exposed to pesticides during their routine work in agriculture are at risk of reduced blood ChE activity. Diphenhydramine appeared to partially protect blood ChE in vitro from additional carbaryl-induced enzyme inhibition in both pesticide-exposed and unexposed subjects. [ABSTRACT FROM AUTHOR]

Abstract: The teenage population is highly vulnerable to drug exposure, use, and misuse due to the physical and emotional development that occurs at those ages. Social influences, like the isolation experienced during the COVID-19 pandemic and social media, can exacerbate this vulnerability. To better understand the potential impact of these influences on teenage drug use, postmortem results reported by a large reference laboratory from 2017 to 2021 corresponding to the teenage population were evaluated for various drugs of misuse. These data revealed a marked increase (385%) in reported fentanyl cases and a 13% increase in positivity rate. Methamphetamine- and cocaine-positive cases also increased 126% and 54%, with a net percent positivity of +0.6% and -0.5%, respectively. Conversely, heroin showed a consistent decline in reported cases (67%) and a net decrease of 1.0% in positivity rate. In addition to commonly misused drugs, trends for other substances that are prevalent in social media and therefore may disproportionally impact teens, MDMA/MDA, mitragynine, and diphenhydramine, were also assessed. A discussion of drug-related social media trends is presented to provide additional context for the data and trends reported herein, ultimately creating a framework through which social influences on teenage drug use can be better understood., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Carvacrol is a natural antioxidant possessing various biological properties. Diphenhydramine is a first-generation antihistamine prescribed for allergies and the common cold. Recently, investigations have shown that diphenhydramine might cause genotoxicity. Antioxidants significantly act in defending cells against oxidative induced genotoxicity. Here, we assessed the protective effect of carvacrol, as a potent antioxidant, on diphenhydramine induced oxidative genotoxicity on human peripheral blood lymphocytes. Methods: Peripheral lymphocytes were treated as followed groups: diphenhydramine concentrations (200, 500 and 1000 µg/mL), diphenhydramine in combination with carvacrol (5 µg/mL), cisplatin (0.05 µg/mL) and cisplatin in combination with carvacrol. We evaluated the formation of micronucleus (MN), known as genotoxicity occurrence indicator, to demonstrate the possibility of diphenhydramine-induced genotoxicity. Furthermore, the level of oxidative stress was assumed by cellular glutathione oxidation and lipid peroxidation. Results: The results showed that high concentrations of diphenhydramine could cause oxidative stress damages by elevating the lipid peroxidation and glutathione oxidation. The frequency of micronucleus increased after diphenhydramine exposure (p < 0.05). Interestingly, carvacrol significantly decreased frequency of micronucleus and lipid peroxidation in lymphocytes exposed to high concentration of diphenhydramine. Conclusion: Our results further support the idea that carvacrol has beneficial effects in protecting cells against oxidative stress damages and diphenhydramine-induced genotoxicity.

Lipid emulsion therapy (LET) has been most thoroughly studied to reverse local anesthetic systemic toxicity (LAST). Case reports suggest that LET can successfully rescue cardiovascular collapse from bupropion, amitriptyline, and propranolol. The efficacy of LET against refractory hypotension and dysrhythmias from diphenhydramine, a commonly ingested lipophilic cardiotoxic agent, is less well described. Summarize the evidence that LET rescues cardiac ion channel blockade (QRS, QTc widening) or hypotension attributable to diphenhydramine overdose. We searched MEDLINE, EMBASE, and Google Scholar for English-language full-length case reports of diphenhydramine (DPH) intoxication in patients 17 years of age or older. We extracted data with a PRISMA-compliant protocol, dividing the case reports into two groups, one that received LET and one that did not. We performed a pooled analysis to compare the change in mean arterial pressure (MAP), QRS duration, and QTc duration between the two groups. We identified 23 reports (25 patients). Lipid emulsion therapy (LET) was used in 6 cases because the patient suffered from hypotension refractory to traditional resuscitation. Those who received LET and those who did not were comparable in age, gender, amount ingested, and frequency of seizures. The mean arterial pressure (MAP) decreased by 4.5 ± 11.5 mm Hg in those who did not receive LET compared to an increase in MAP 37 ± 17.5 mm Hg in those who did receive LET. The QRS narrowed by 29 ± 33.9 ms (no LET group) vs 68 ± 49.5 ms (LET group) and QTc by 168.5 ± 126.75 ms (no LET group) vs 134 ± 88 ms (LET group). All values are expressed as median ± interquartile range. One out of the 6 patients who received LET died after withdrawal of care. In the group that did not receive LET 4 out of 19 died and 3 had no outcome reported. LET may improve MAP in patients with hypotension refractory to vasopressors due to diphenhydramine toxicity. We found no significant effect of LET on QRS or QTc duration. These results are limited by a small sample size, reporting bias of case reports, incomplete data, and heterogeneity. An analysis of pooled case reports suggests that LET may rescue hypotension when other methods have failed in patients with hypotension attributable to diphenhydramine overdose. [ABSTRACT FROM AUTHOR]

Acute dystonia has notably been a challenge in the emergency unit. Drug-induced dystonia is reported in a limited number of cases in the literature. Rarely, diphenhydramine was found to be the culprit. We report the case of a 25-year-old female patient who developed an acute dystonic reaction following the administration of 25 mg of intravenous diphenhydramine as a treatment for an allergic reaction. The patient was given 5 mg diazepam, admitted for monitoring, and discharged home. Diphenhydramine-induced acute dystonia is a user drug-induced threatening reaction that warrants further investigation on the metabolism of these drugs and the contributing phenotypes to this adverse reaction. [ABSTRACT FROM AUTHOR]

This report addresses studies of the release of active ingredients (diphenhydramine and fluconazole) from a gel base for a medicine for external application for the treatment of allergy complicated by fungal infection; its toxicological and morphological properties were studied. The gel composition was found to be a medicinal formulation providing complete release of the active components from the gel: the quantity of diphenhydramine released in 3 h approached 75%, while the quantity of fluconazole approached 72%. Active substances are easily released from this formation on application to the skin surface, with accumulation of drug to high concentrations at the lesion site. The gel composition was found to belong to class VI, relatively harmless substances, without toxic or cumulative actions. Skin histology results from experimental animals confirmed rapid regeneration of skin lesions on external application of the gel composition. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic and sedative combinations are commonly used for treating agitation in the emergency department despite limited evidence regarding their comparative safety and efficacy.Objectives: To compare the efficacy and safety of combination haloperidol, lorazepam, and diphenhydramine (B52) to combination haloperidol and lorazepam (52) in treating acute agitation.Methods: This multicenter, retrospective cohort study included adult patients ≥ 18 years of age who received either B52 or 52 at a Banner Health facility between August 2017 and September 2020. Patients were excluded if they had a pre-existing movement disorder or were withdrawing from alcohol. The primary outcome was administration of additional agitation medication(s) within 2 h of B52 or 52. Secondary outcomes included incidence of extrapyramidal symptoms, length of stay, and additional safety measures.Results: There was no difference in administration frequency of additional agitation medication(s) (B52: n = 28 [14%] vs. 52: n = 40 [20%]; p = 0.11). Patients who received 52 were more likely to require an antimuscarinic medication within 2 days (15 vs. 6 patients, p = 0.04). Of the patients who received an antimuscarinic medication, none had documented extrapyramidal symptoms. The 52 group had shorter length of stay (13.8 vs. 17 h; p = 0.03), lower incidence of hypotension (7 vs. 32 patients; p < 0.001), and oxygen desaturation (0 vs. 6 patients; p = 0.01), and fewer physical restraints (53 vs. 86 patients; p = 0.001) compared with the B52 group.Conclusions: Both the B52 and 52 combinations infrequently required repeat agitation medication; however, the B52 combination resulted in more oxygen desaturation, hypotension, physical restraint use, and longer length of stay. [ABSTRACT FROM AUTHOR]

T2R bitter taste receptors in airway motile cilia increase ciliary beat frequency (CBF) and nitric oxide (NO) production. Polymorphisms in some T2Rs are linked to disease outcomes in chronic rhinosinusitis (CRS) and cystic fibrosis (CF). We examined the expression of cilia T2Rs during the differentiation of human nasal epithelial cells grown at air–liquid interface (ALI). The T2R expression increased with differentiation but did not vary between CF and non-CF cultures. Treatment with Pseudomonas aeruginosa flagellin decreased the expression of diphenhydramine-responsive T2R14 and 40, among others. Diphenhydramine increased both NO production, measured by fluorescent dye DAF-FM, and CBF, measured via high-speed imaging. Increases in CBF were disrupted after flagellin treatment. Diphenhydramine impaired the growth of lab and clinical strains of P. aeruginosa, a major pathogen in CF and CF-related CRS. Diphenhydramine impaired biofilm formation of P. aeruginosa, measured via crystal violet staining, as well as the surface attachment of P. aeruginosa to CF airway epithelial cells, measured using colony-forming unit counting. Because the T2R agonist diphenhydramine increases NO production and CBF while also decreasing bacterial growth and biofilm production, diphenhydramine-derived compounds may have potential clinical usefulness in CF-related CRS as a topical therapy. However, utilizing T2R agonists as therapeutics within the context of P. aeruginosa infection may require co-treatment with anti-inflammatories to enhance T2R expression. [ABSTRACT FROM AUTHOR]

Purpose: Cetirizine is a less sedative alternative to diphenhydramine for the prevention of infusion-related reactions (IRR) to paclitaxel. However, its use remains controversial. In this study, we assessed feasibility for a future definitive non-inferiority trial comparing cetirizine to diphenhydramine as premedication to prevent paclitaxel-related IRR. Methods: This was a single-center randomized prospective feasibility study. Participants were paclitaxel-naive cancer patients scheduled to start paclitaxel chemotherapy. They were randomly assigned to receive either intravenous diphenhydramine 50 mg + oral placebo (control) or intravenous placebo + oral cetirizine 10 mg (intervention) for their first two paclitaxel treatments. The percentage of eligible patients completing a first paclitaxel treatment and the recruitment rate were assessed (feasibility outcomes). Drowsiness was measured at baseline and at selected time points using the Stanford Sleepiness Scale (SSS) (safety outcome). IRR events were also documented (efficacy outcome). Results: Among 37 eligible patients, 27 were recruited and randomized (control 13; intervention 14) and 25 completed the study. The recruitment rate was 4.8 participants/month, meeting the primary feasibility target. Drowsiness was the main adverse effect associated with the premedication. The increase in drowsiness compared to baseline (ΔSSS) was greater in the diphenhydramine group compared to the cetirizine group (median ΔSSS 2 (IQR 3.25) vs median ΔSSS 0 (IQR 1), p < 0.01) when measured one hour after the premedication administration. One participant had an IRR and no unexpected serious adverse event occurred. Conclusion: The trial methods were feasible in terms of recruitment, retention, and safety. Cetirizine was significantly less sedating than diphenhydramine. IRR were infrequent and a larger trial is warranted to confirm non-inferiority for IRR prevention. Trial registration: ClinicalTrials.gov, NCT04237090 (22.01.2020). [ABSTRACT FROM AUTHOR]

In this study, pristine MIL101(Cr) was modified to synthesize hydroxyl-functionalized (MIL101(Cr)-OH) and chitosan (CS)-coated (MIL101(Cr)-OH/CS) metal-organic frameworks (MOFs) to enhance adsorption capacity and reusability, respectively. The synthesized adsorbents were characterized by XRD, FTIR, and BET analyses. The kinetics behavior and the equilibrium adsorption of diphenhydramine (DPH) and metronidazole (MNZ) from aqueous solution on the synthesized adsorbents and a commercial activated carbon were compared at 25°C. The pH-dependent of the adsorption capacity and reusability of MIL101-OH/CS were investigated. The results showed that upon adding OH functional group and chitosan polymer, the adsorption capacity increased; the DPH adsorption capacity on MIL101-OH and MIL101-OH/CS was 634 and 573 mg/g, respectively. Also, the maximum adsorption capacity of MNZ on MIL101-OH/CS was 600 mg/g, which was twice the adsorption capacity of MIL101 and four times the adsorption capacity of the commercial activated carbon. The equilibrium and kinetics behavior results were in good agreement with Langmuir and the pseudo-second-order models, respectively. The DPH and MNZ adsorption mechanisms on MIL101-OH/CS were hydrogen bonding and electrostatic interactions, respectively. [ABSTRACT FROM AUTHOR]

Diphenhydramine (DIPH) has become one of the world's most widely abused over‐the‐counter medications. In addition to relieving allergy symptoms, it is also recognized for causing elevated energy and mild euphoric effects. The U.S. Food and Drug Administration (FDA) has recently warned about serious problems at high doses including heart problems, seizures, coma or even death among addicted teenagers. Herein, a simple, cost‐effective, and reliable nanocomposite based electrochemical sensor was designed for DIPH quantification in biological fluids. Introducing the functionalized Fe3O4 nanoparticles (NPs) into the inner‐filling solution and the PVC‐based ion sensing membrane has been employed and compared to the classical potentiometric approach. The nanoparticles were incorporated to endorse in situ cooperative ion‐pairing interaction between the ionophore and DIPH, and to improve the selectivity and detection limit (9.5×10−8 M). Nernstian potentiometric response was achieved for DIPH over the concentration range of 1.0×10−7 to 1.0×10−2 M with a slope of 59.0±0.2 mV/decade. Inherent merits of the proposed sensor include fast response time (6 s), superior stability (60 days) with higher sensitivity and selectivity towards DIPH without interference from co‐formulated drugs and several ions commonly found in biological matrices. The proposed sensor was successfully applied to the potentiometric determination of DIPH in different biological fluids (plasma and human milk) with an average recovery of 99.06±1.95 % and 100.34±1.92 %, respectively. As a consequence, the developed ISE might be the ideal choice for in‐line DIPH measurements in plasma samples to identify overdose ingestion and its related symptoms, as well as for quality‐control laboratories without prior treatments. [ABSTRACT FROM AUTHOR]

Dimenhydrinate (DMH) is a salt composed by the combination of two active pharmaceutical ingredients: diphenhydramine (DIP) and 8-chlorotheophylline (CTP). In this work, the glassy carbon electrode was electrochemically deposited in two steps. The electrode was first inserted in the Alizarin Yellow R (AYR) solution and it was placed on the surface of the electrode after 8 scans. In order to modify the electrode with copper nanoparticles, the prepared electrode was first inserted into the copper sulfate solution and coated with copper nanoparticles using cyclic voltammetry CuNps/PAYR/GCE was fabricated. SEM images showed that the copper nanoparticles were deposited on the electrode. The electrocatalytical effects of the electrochemical sensor were also studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. This electrode was used for detection simultaneously of DIP (OX1) and CTP (OX2) in pharmaceutical samples. The results showed that the highest sensitivity for DMH was obtained at pH = 10. Finally, Also, the detection of limit, sensitivity and linear range were calculated as 0. 29 µM, 0.043 and 1–3000 µM respectively. CuNps/PAYR/GCE presented considerable advantages for instance high sensitivity, used for real samples, simple preparation, low detection of limit, and specially the simultaneous oxidation of CTP and DIP for detection of DMH. [ABSTRACT FROM AUTHOR]

Background: Emergence agitation after maxillofacial surgeries is an anxious and problematic complication for the surgeon and anesthesiologist that may lead to self-extubation, haemorrhage, and surgical destruction. In this study, we investigated the effects of preemptive administration of diphenhydramine on emergence agitation and quality of recovery after maxillofacial surgery in adult patients. Methods: Eighty-five patients undergoing maxillofacial surgery were randomized into two groups. The diphenhydramine group (Group D, n = 40) received diphenhydramine premedication 0.5 mg/kg before anesthesia induction, while the control group (Group C, n = 40) received volume-matched normal saline as a placebo. Before incision, all patients receive 0.1 mg/kg morphine sulfate slowly intravenously within 5 min. Continuous infusion of remifentanil 0.2 μg/kg/h and inhalation of isoflurane was maintained during the anesthesia period. Paracetamol 1 g was infused 15 min before extubation. We evaluated the incidence of agitation during the extubation period after general anesthesia, hemodynamic parameters, and recovery characteristics during the postoperative period. Results: During extubation time, the incidence of emergence agitation was lower in Group D than in Group C (16% vs. 49%, P = 0.041). The time from isoflurane discontinuation to extubation (7.7 min in Group D vs. 6.8 min in Group C, P = 0.082) was not different. Grade of cough during emergence, the severity of pain, analgesic requirements, and hemodynamic changes were lower in group D compared with Group C. Conclusions: Preemptive administration of diphenhydramine provided smooth emergence from anesthesia. It also improved the quality of recovery after maxillofacial surgery. Trial registration number: This study was registered at http://irct.ir (registration number IRCT20130304012695N3). [ABSTRACT FROM AUTHOR]

Diphenhydramine is an H1 receptor antagonist used to control urticaria and other allergic signs caused by type I hypersensitivity reactions in horses (Equus caballus). Limited studies have been conducted on pharmacokinetics of this drug in horses, with no studies involving oral formulations. Our study investigated pharmacokinetics of an oral diphenhydramine formulation compared to intravenous administration in non‐fasted adult horses. Six healthy horses underwent a single administration of three different doses of diphenhydramine (1 mg/kg intravenously, 1 mg/kg intragastrically, and 5 mg/kg intragastrically) with a two‐week washout period between doses. Bioavailability of intragastric diphenhydramine was less than one percent and six percent for 1 mg/kg and 5 mg/kg intragastric doses, respectively. This poor bioavailability is similar to what is reported in dogs. Two of six horses experienced transient side effects after intravenous diphenhydramine administration, emphasizing the need for determining therapeutic plasma levels in efforts to determine the lowest effective dose minimizing risk of adverse effects. The main conclusion of our study was that oral diphenhydramine at doses up to 5 mg/kg are unlikely to achieve therapeutic plasma levels in adult horses. [ABSTRACT FROM AUTHOR]