Search

In continuation of the search for effective, economical, and environmental methods of synthesizing the antihistamine agent diphenhydramine, alkylation of dimethylethanolamine by bromo- (or chloro-)diphenylmethane under phase-transfer catalysis (PTC) conditions and in a microwave oven was studied. The efficiencies of a two-phase liquid(liquid system and a solid-phase(liquid system were compared. The quaternary ammonium salt tetrabutylammonium bromide (TBAB) was used as a catalyst. The proposed microwave irradiation was found to be effective and allowed diphenhydramine to be synthesized in a short time in high yield and purity, suggesting that the proposed method could be used in practice. [ABSTRACT FROM AUTHOR]

In this research, a new Lewis acid-based deep eutectic solvent (LA-DES) was synthesized using diphenhydramine hydrochloride and CoCl2·6H2O, (2[HDPH]:CoCl42−), and identified by FT-IR and 1HNMR techniques. The physicochemical properties of this LA-DES, such as thermal behavior, thermal stability, and solubility in common solvents were also investigated. The catalytic ability of 2[HDPH]:CoCl42− was ascertained in the efficient synthesis of a novel array of thiadiazolo[2,3-b]quinazolin-6-one scaffolds via a one-pot three-component reaction of dimedone/1,3-cyclohexanedione, aldehydes, and 5-aryl-1,3,4-thiadiazol-2-amines/3-(5-amino-1,3,4-thiadiazol-2-yl)-2H-chromen-2-one under solvent-free conditions. This catalyst was also successfully utilized for the synthesis of mono- and bis-thiadiazolo[2,3-b]quinazolin-6-ones from dialdehydes or bis-1,3,4-thiadiazol-2-amine. The simplicity of enforcement, short reaction time, avoidance of toxic organic solvents, scalability of the synthesis procedure, excellent atom economy, high reaction mass efficiency, and low E-factor are other outstanding advantages of this newly developed method. Furthermore, due to the convenient recovery and reuse of LA-DES, this protocol is economically justified and environmentally friendly. [ABSTRACT FROM AUTHOR]

The determination of mitragynine and psychoactive substances in kratom drinks is essential for forensic investigation and medical treatment. In this study, gas chromatography coupled with flame ionization was used to identify mitragynine, caffeine, diphenhydramine, promethazine, and tramadol in various kratom drinks. The analysis was conducted using the HP‑5 column with a nitrogen gas flowing at a rate of 1.8 mL/min. The oven temperature was held at 220°C for 1 min and then increased to 270°C at a rate of 5°C/min. It was further ramped to 300°C at a rate of 30°C/min and held for 13 min. The injector and detector temperatures were set at 280°C. Samples were injected using the split mode (50 : 1) and the total run time was 25 min. Alkalinized samples were extracted with an 80 : 20 (v/v) mixture of ethyl acetate and n-hexane. Method validation revealed acceptable linearity for all analytes (r > 0.990), good precision (0.7–4.2% RSD), accuracy (–11.0–15.2% RE), lower limit of quantification (3–15 µg/mL), and extraction recoveries (81.8–105.8%, except caffeine). The developed method successfully detected and quantified the target analytes. [ABSTRACT FROM AUTHOR]

This study investigated photocatalytic degradation of pharmaceutical compound using CuO or PdO–TiO2 membrane. The synthesized membranes were characterized by some techniques including X-ray powder diffraction (XRD), dynamic light scattering (DLS), scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FT-IR). The structural properties confirmed that the photocatalytic membranes were successfully prepared on ceramic supports. The PdO-TiO2 and CuO-TiO2 membranes were employed as photocatalytic membranes to degrade metronidazole (MNZ) and diphenhydramine (DPH) in aqueous solutions, respectively. Some parameters affecting the photocatalytic reaction such as pH, initial concentration, and light source were also investigated. The maximum degradation for both pharmaceutical compounds was obtained at basic pH (pH = 10), low initial concentration (C0 = 10 ppm) under UV irradiation. At high transmembrane pressure (ΔP = 3 bar), the flow rate across the membrane increased up 0.0078 and 0.0082 cc/s.cm2 for CuO-TiO2 and PdO-TiO2 photocatalytic membrane respectively while not affected on degradation efficiency (DE). At the same condition operation (C0 = 10 ppm, pH = 10, ΔP = 2 bar under UV irradiation), the MNZ and DPH degradation of the PdO-TiO2 membrane was 94 and 95% respectively that relatively higher than the CuO-TiO2 membrane. It is probably due to the lower energy band gap of PdO-TiO2 (2.5 eV) than CuO-TiO2 (2.7 eV). The membrane stability tests confirmed the high performance of the prepared membranes. [ABSTRACT FROM AUTHOR]

A simple, sensitive, and rapid bioanalytical method was developed for the first time for simultaneous estimation of naproxen sodium (NPX) and diphenhydramine hydrochloride (DPH) in human plasma using liquid chromatographytandem mass spectrometry (LC–MS/MS). The isotope-labelled analogs, naproxen 13CD3 and diphenhydramine D5 hydrochloric acid, were used as the internal standards. The analytes were extracted from 50 μL of human plasma employing a simple protein precipitation technique. The separation of analytes was carried out on a Zodiac C18 column (50 × 4.6 mm, 3 μm) using a mixture of HPLC grade acetonitrile and 5 mM ammonium acetate buffer in 0.025% formic acid (60:40, v/v) at a flow rate of 1.0 mL/min. The method showed linearity within the concentration ranges 400 to 120,000 ng/mL for NPX and from 0.80 to 240 ng/mL for DPH with r2 > 0.99. The method was validated as per the US FDA guidelines and the results were found to be within the acceptance limits. The method was successfully applied for the pharmacokinetic study of both drugs simultaneously after an oral dose of two caplets, each containing NPX 220 mg and DPH 25 mg under fed conditions in human volunteers. Incurred sample reanalysis was also performed to authenticate the reproducibility of the method. [ABSTRACT FROM AUTHOR]

Embryonic-fetal developmental toxicity of compounded diphenhydramine hydrochloride (DH) and caffeine formulation has been studied by intragastric administration to pregnant SD rats. Between days 6 and 15 of pregnancy, SD rats in different groups received a low-, medium-, and high-dose of binary formulation containing DH and caffeine (DHC), a single-medication formulation containing DH, or a single-medication formulation containing caffeine. No animal deaths or clinical toxicity manifestations related to these treatments were observed in any test group. Three test groups treated with DHC formulation, as well as the DH group, showed no apparent drug influence on the body weight of pregnant rats. However, the use of caffeine alone had an impact on the body weight gain of pregnant rats (P < 0.05), which indicated maternal toxicity. The single use of caffeine alone had an impact on the food intake during pregnancy, and the food intake was recovered after medication discontinuation (P < 0.05). Except for the caffeine group, the three compounded formulation dose groups and the DH group exhibited no apparent embryonic toxicity (P > 0.05). Besides, the administration of caffeine to pregnant rats (144 mg/kg) caused fetal toxicity and influenced fetal sternal development (P < 0.05). The low, medium, and high doses of compounded DHC formulation and the single-medication DH formulation caused neither adverse reactions in pregnant rats nor impeded embryonic and fetal development. However, a single-medication formulation containing caffeine at a dose of 144 mg/kg caused toxicity to pregnant rats as well as to embryonic and fetal development. [ABSTRACT FROM AUTHOR]

Introduction: Recurrent physostigmine shortages present a challenge to healthcare providers treating antimuscarinic delirium. Other centrally acting acetylcholinesterase inhibitors such as rivastigmine may represent a therapeutic alternative or adjunct during physostigmine shortage; however, previous reports of use have not documented serum antimuscarinic toxin concentrations, limiting evaluation of effectiveness. Combination therapy with physostigmine and rivastigmine has not been described. In this report, the authors present a case of diphenhydramine-induced antimuscarinic delirium with elevated diphenhydramine serum concentrations treated with physostigmine and transdermal rivastigmine without observed adverse effect. Case Report: A 48-year-old female presented to an emergency department after ingesting 3.75 g (41.2 mg/kg) of diphenhydramine. She had antimuscarinic delirium with a presenting serum diphenhydramine concentration of 1500 ng/mL (therapeutic range, 25–112 ng/mL) and required two doses of physostigmine to avert intubation prior to intensive care unit (ICU) admission. At hospital hour 22, in the ICU, antimuscarinic delirium persisted but no further physostigmine was available due to hospital shortage. Therefore, a 9.5-mg transdermal rivastigmine patch was applied. By hospital hour 24, her delirium had resolved. A serum diphenhydramine concentration at hospital hour 25 was elevated at 760 ng/mL. Transdermal rivastigmine was discontinued at hospital hour 48 without recurrent delirium. Despite persistent normal mental status after rivastigmine discontinuation, the patient had a dry mouth, difficulty urinating, and mydriasis until hospital day 5. She never developed muscarinic toxicity. Discussion: Transdermal rivastigmine may be a useful treatment alternative or adjunct during physostigmine shortage for antimuscarinic delirium and has a long duration of action without aspiration risk. Muscarinic toxicity was not observed. [ABSTRACT FROM AUTHOR]

A method for accelerated determination of diphenhydramine hydrochloride (dimedrol, DPH) in liquid and solid dosage forms (DFs) that is based on titration of the analytical form with a solution of photogenerated iodine obtained by irradiation of an auxiliary solution containing potassium iodide and uranine at pH 6.0 has been developed. Stabilization of the current in the amperometric circuit indicated that the reaction was complete and; therefore, provided control of the DPH content in the DF because the titrant content in the solution was controlled by a voltammetric method (amperometric titration with two polarized electrodes). Further irradiation of the solution and measurement of the time required to regenerate the lost titrant also made it possible to regulate the DPH content in the DF. The technique was tested on a solid DF and sterile solutions of DPH intended for intramuscular and intravenous administration. Stabilizers (HCl, lactose monohydrate) present in the DF had insignificant effects on photogeneration of the titrant. The dependence of the analytical signal on DPH concentration was linear in the range 0.1 – 20.0 mg for the drug "Diphenhydramine, tablets 50 mg." The limits of detection (DL) and quantitation (LOQ) for this drug that were calculated from the changes in the current and regeneration time were (1.26; 0.108) mg and (0.382; 0.329) mg, respectively. The developed photochemical method of determination complies with the requirements in the guidelines for validation of bioanalytical methods. The method is easy to use and does not require expensive equipment. Therefore, it can be recommended for routine control of the quality indicators under control or analytical laboratory conditions. [ABSTRACT FROM AUTHOR]

The document titled "Correction to: Rhabdomyolysis following diphenhydramine overdose—a case report" in Skeletal Radiology addresses corrections to the author group and affiliations. The correct author group includes Adil Basha, Rifat Karatas, Atul Kumar Taneja, Avneesh Chhabra, and Flavio Duarte Silva. The corresponding author is Flavio Duarte Silva, and the correct affiliations are listed accordingly. The original article can be accessed online for further reference. [Extracted from the article]

Antihistamines, such as diphenhydramine, are active ingredients of a wide variety of antiallergics, sedatives, and sleep preparations and are often abused for purposes of euphoric effects or suicidal attempts. Antihistaminic overdose presents with symptoms of increased anticholinergic activity including urinary retention, mydriasis, and dry mucous membranes. However, antihistamine-induced rhabdomyolysis is a rare condition that presents with widespread skeletal muscle breakdown and release of metabolites into the circulation, resulting in myalgias and acute kidney injury. In this article, we report a rare case of rhabdomyolysis following the ingestion of a large quantity of diphenhydramine for a suicide attempt, who also presented with significantly elevated creatine kinase and acute renal injury. To our knowledge, this is the first case report of diphenhydramine rhabdomyolysis with MRI findings’ correlation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the safety and efficacy of Rest-ZZZ, a natural sleep supplement, in healthy adults without a diagnosed sleep disorder. This randomized, double-blind, placebo-controlled, cross-over study consisted of three 7-day supplementation periods with either Rest-ZZZ, Diphenhydramine (DPH), or Placebo, with a 7-day washout. Twenty-seven participants were randomized to one of three intervention sequences and the Healthy People Sleep Quality Index (HPSQI), Quality of Life (QoL), and Profile of Mood States (POMS) questionnaires were assessed at the beginning and end of each supplementation period. Rest-ZZZ and Placebo showed improvements in sleep-related QoL (p ≤ 0.044) and total mood disturbance (TMD) (p = ≤ 0.028). Fatigue–Inertia was reduced by all study products (p ≤ 0.031). DPH did not result in any significant improvements on sleep quality parameters. A subgroup analysis of participants ≤ 45 years found enhanced efficacy of Rest-ZZZ and improvement in sleep-related QoL vs. Placebo (p = 0.007), as well as improvements in sleep duration (p = 0.007), sleep debt (p = 0.011), and sleep-related QoL (p = 0.033). DPH supplementation resulted in significant improvement in only sleep debt (p = 0.038). Rest-ZZZ had a safe hematology and chemistry profile. Rest-ZZZ resulted in restful sleep that generated corresponding improvements in sleep-related QoL and overall mood. Rest-ZZZ is an efficacious sleep supplement with a favorable safety profile, particularly in those aged 25–45 years. [ABSTRACT FROM AUTHOR]

Purpose: Diphenhydramine is an antihistamine drug widely used to alleviate symptoms caused by allergies and the common cold. Diphenhydramine-involved fatalities have been reported in the past but usually involving overdose by ingestion. We report a peculiar case of fatal hypothermia during non-winter season involving topical diphenhydramine. Methods: A 23-year-old male with no known preexisting medical conditions was found dead in the bathroom of his apartment with a small amount of running water on his back. Postmortem examinations and toxicological analysis on blood and urine were performed. Results: Color difference was apparent between the right and left cardiac blood. Wischnewski spots were observed in the gastric mucosa. Histological examination revealed no obvious findings that could attribute to serious cardiovascular events. Drug screening by gas chromatograph-tandem mass spectrometry (GC/MS/MS) detected diphenhydramine in blood and urine. Further quantification revealed the postmortem concentrations to be 0.44 μg/mL in blood and 2500 μg/mL in urine. Conclusions: The cause of death was determined to be hypothermia. Diphenhydramine-induced drowsiness and possible intrinsic cardiac factor may have led to prolonged impaired consciousness, preventing his ability to escape from the running cold water leading to hypothermia and death. [ABSTRACT FROM AUTHOR]

The development of visible light-responsive metal-doped TiO2 for the treatment of water and wastewater has gained much attention. Herein, TiO2/Ag nanocatalyst thin films stabilized on glass was successfully obtained by a simple sol–gel method. The morphology, crystalline and functional structure, bandgap energy, and optical properties of synthesized TiO2/Ag were studied by XRD, FTIR, FESEM-EDX, and UV–Vis DRS analyses. The results showed that the size of most of the nanoparticles was between 20 and 40 nm. Besides, the red shift to the visible region and the reduction of bandgap energy to 2.7 eV were observed as a result of the modification of TiO2 by Ag. The diphenhydramine (DPH) and venlafaxine (VNF) photodegradation efficiency were studied using the TiO2/Ag/UV–Vis process with independent variables by the response surface methodology (RSM). The proposed RSM models with high R2 (0.996–0.997) confirmed a satisfactory correlation between the experimental results and predicted values. The RSM results showed the significant inhibitive effects of increasing antibiotic concentration on the removal efficiency, whereas the highest positive impacts on the degradation efficiency were obtained by increasing the irradiation time. More than 70% of drugs were removed under optimum conditions (20 mg/L of initial VNF (DPH) concentration, pH of 10 under 180 min illumination). [ABSTRACT FROM AUTHOR]

Currently, all researchers are concentrating their efforts on countering the COVID-19 pandemic. The majority of patients are managed at home, according to recent statistics. An OTC triple action combination comprising paracetamol (PAR), aspirin (ASP), and diphenhydramine (DIPH) is commonly given for pain relief, fever control, and as a night-time sleep aid. This combination is currently recommended for COVID-19 patients as part of symptomatic treatment and management. In this work, three smart, simple, accurate, eco-friendly, and cost-effective spectrophotometric methods are developed for simultaneous determination of PAR, ASP, and DIPH in their combined over-the-counter caplet dosage form without any prior separation steps. The first method is the first derivative spectrophotometry (D1) which determined PAR at 259.7 nm. The second one is the dual-wavelength in ratio spectra (DWRS) for determination of ASP at 214.1 and 220.1 nm after using 10.0 μg/mL of PAR as a divisor, where PAR was a constant, and the wavelengths difference equal to zero for DIPH. The third method is the double divisor-ratio difference spectrophotometric one (DD-RD) which was based on using the sum of 15.0 µg/mL of each of PAR and ASP as a double divisor, and the difference in amplitudes was measured at two wavelengths ∆P(214.5–226.0) for determination of DIPH. The developed methods have been validated as per ICH guidelines. Furthermore, the three suggested methods were employed successfully to assay marketed pharmaceutical formulation and to investigate the content uniformity of the dosage units in accordance with the United States Pharmacopeia's guidelines. Finally, the greenness profile of the proposed methods was assessed and compared with the reported method using the analytical eco-scale system, national environmental method index (NEMI), green analytical procedure index (GAPI), and analytical greenness (AGREE) metric. The results from the proposed methods statistically agreed with those obtained by the reported one, with no significant differences in accuracy and precision. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

Thomas Dahl, PO Box 404, Guilford, CT 06437 USA. Email: tadahl@outlook.com. The objectives of the study were to demonstrate the efficacy and safety of SM-1 in a circadian challenge model of transient insomnia. Randomized, double-blind, placebo-controlled cross-over study utilizing a 5-h phase advance model of transient insomnia. Subjects were 85 healthy adults reporting a history of transient insomnia, with an average age of 38.9 years. Both SM-1 and placebo were administered to all subjects in a randomly assigned sequence, with at least 1 week between treatments. The primary endpoint was total sleep time determined by polysomnography. Secondary endpoints included wakefulness after sleep onset, latency to persistent sleep, number of awakenings, subjective total sleep time and subjective sleep onset latency, total sleep time by quarters of the night, subjective number of awakenings, and sleep quality. Safety endpoints included adverse events, Karolinska Sleepiness Scale, Digit Symbol Substitution Test, and predischarge evaluation (tandem gait and Romberg tests). SM-1 provided an increase of 94.4 min in total sleep time over placebo (p < 0.0001). Wakefulness after sleep onset, subjective total sleep time, subjective sleep onset latency, and total sleep time in the first quarter of the night also showed significant improvement. SM-1 was well-tolerated with both type and frequency of adverse events being comparable to placebo, and no residual sleepiness upon awakening (i.e., after 8 h). SM-1 provided a robust and statistically significant increase in total sleep time compared to placebo in a circadian model of transient insomnia, without evidence of next-day impairment. [ABSTRACT FROM AUTHOR]

Since 1955, the only available H1 antihistamines for intravenous administration have been first-generation formulations and, of those, only intravenously administered (IV) diphenhydramine is still approved in the USA. Orally administered cetirizine hydrochloride, a second-generation H1 antihistamine, has been safely used over-the-counter for many years. In 2019, IV cetirizine was approved for the treatment of acute urticaria. In light of this approval, this narrative review discusses the changing landscape of IV antihistamines for the treatment of histamine-mediated conditions. Specifically, IV antihistamines will be discussed as a treatment option for acute urticaria and angioedema, as premedication to prevent infusion reactions related to anticancer agents and other biologics, and as an adjunct treatment for anaphylaxis and other allergic reactions. Before the development of IV cetirizine, randomized controlled trials of IV antihistamines for these indications were lacking. Three randomized controlled trials have been conducted with IV cetirizine versus IV diphenhydramine in the ambulatory care setting. A phase 3 trial of IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 262 adults who presented to the urgent care/emergency department with acute urticaria requiring antihistamines. For the primary efficacy endpoint, defined as change from baseline in a 2-h patient-rated pruritus score, non-inferiority of IV cetirizine to IV diphenhydramine was demonstrated (score - 1.6 vs - 1.5, respectively; 95% CI - 0.1, 0.3). Compared with IV diphenhydramine, IV cetirizine demonstrated fewer adverse effects including less sedation, a significantly shorter length of stay in the treatment center, and fewer returns to the treatment center at 24 and 48 h. Similar findings were demonstrated in another phase 2 acute urticaria trial and in a phase 2 trial assessing IV cetirizine for pretreatment for infusion reactions in the oncology/immunology setting. IV cetirizine is associated with similar patient outcomes, fewer adverse effects, and increased treatment center efficiency than IV diphenhydramine. [ABSTRACT FROM AUTHOR]

Purpose: Drug distribution in scalp hair can provide historical information about drug use, such as the date and frequency of drug ingestion. We previously developed micro-segmental hair analysis, which visualizes drug distribution at 0.4-mm intervals in individual hairs. The present study examines whether the distribution profiles of drugs can be markers for the administration or external contamination of the drugs using scalp, axillary, and pubic hairs. Methods: A single dose of anti-itch ointment containing diphenhydramine (DP) and lidocaine (LD) was topically applied to the axillary or pubic areas of two volunteers; DP was also orally administered; and LD was intra-gingivally injected. Scalp, axillary, and pubic hairs were assessed using our micro-segmental analysis. Results: The localization of DP and LD differed within individual scalp hair strands, implying DP and LD were predominantly incorporated into scalp hair via the bloodstream and via sweat/sebum, respectively, showing double-peak profiles. However, DP and LD were distributed along the shafts of axillary and pubic hairs without appearance of the double-peak profiles when the ointment had been applied to the axillary and pubic areas. The distributions of DP and LD in scalp hairs did not significantly differ according to administration routes, such as oral administration, gingival injection, and topical application. Conclusions: Micro-segmental analysis revealed differences in the distribution profiles of drugs in hairs, and distinguished hairs with and without external contamination. These findings will be useful for understanding of the mechanism of drug uptake into hair and for estimating the circumstances for a drug use. [ABSTRACT FROM AUTHOR]

Purpose: Postoperative nausea and vomiting (PONV) and pain following bariatric surgery are problematic and affect the outcome of patients. Intraoperative multimodal antiemetic prophylaxis is essential to improve postoperative outcomes. This study investigated the effect of adding diphenhydramine to acetaminophen and ondansetron in reducing postoperative nausea and vomiting and pain following laparoscopic sleeve gastrectomy (LSG). Materials and Methods: Eighty-two patients scheduled for LSG were assigned to receive a single preinduction dose of diphenhydramine 0.4 mg/kg VI (D group) in addition to acetaminophen 1g and ondansetron 4 mg IV at the end of surgery and just acetaminophen 1 g and ondansetron 4 mg IV (C group) in a randomized, double-blind trial. PONV was assessed in recovery and 24 hours after surgery in the ward. Postoperative pain, analgesic requirements, and patients' level of sedation were also assessed. Results: The PONV rates in the recovery of the D group and the C group were 30% and 56% (P =.001). It also had a more significant reduction in the D group than in the C group in the first 24 h after surgery (40% vs. 66%). The severity of pain score and level of sedation and analgesic requirements was significantly reduced in this period in the D group. Conclusion: Prophylactic diphenhydramine 0.4 mg/kg at the induction of general anesthesia in combination with acetaminophen 1 g and ondansetron 4 mg at the end of surgery reduced the incidence of PONV and postoperative severity of pain in laparoscopic sleeve gastrectomy. [ABSTRACT FROM AUTHOR]

The first night effect (FNE) is a type of sleep disturbance caused by an unfamiliar environment, which leads to difficulty falling asleep and reduced sleep duration. Previously, we reported that Lactobacillus fermentum PS150 (PS150) improves sleep conditions in a pentobarbital-induced sleep mouse model. In this study, we aimed to evaluate the effect of PS150 on the FNE in mice. Briefly, mice were implanted with electrodes and orally administered PS150 for four weeks, and then the FNE was induced by cage changing. Analysis of polysomnographic signals revealed that intervention with PS150 restored non-rapid eye movement (NREM) sleep length under the FNE. Compared to diphenhydramine, a commonly used sleep aid, PS150 had no unwanted side effects, such as rapid eye movement (REM) sleep deprivation and fragmented sleep. Moreover, temporal analysis revealed that PS150 efficiently reduced both sleep latency and time spent restoring normal levels of REM sleep. Taken together, these results suggest that PS150 efficiently ameliorates sleep disturbance caused by the FNE. Additionally, V3–V4 16S rRNA sequencing revealed significant increases in Erysipelotrichia, Actinobacteria, and Coriobacteriia in fecal specimens of the PS150-treated group, indicating that PS150 induces gut microbiota remodeling. [ABSTRACT FROM AUTHOR]

A technology for treatment of allergies complicated by fungal infection was developed based on Fludigel composition comprising a complex of therapeutic agents including the immunomodulating drug Thymoptin, the antihistaminic drug diphenhydramine, and the antifungal drug fluconazole. Investigation of the specific activity of Fludigel on a model of contact dermatitis complicated by fungal infection showed high activity comparable with that of the combined hormonal ointment Triderm. A comparative assessment of a parameter set of physicomechanical properties and biological activity of the gel composition indicated that clinical studies of the applicability of the developed dosage form in dermatology were expedient. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effectiveness of diphenhydramine, an antihistamine with anti-muscarinic properties, for prevention of postoperative catheter-related bladder discomfort (CRBD). Methods: Ninety-six ASA physical status I and II adult female patients (20–60 years) scheduled for elective gynecologic laparoscopic surgery were included. Patients were randomized into two groups of 48 patients each. All patients received a detailed preoperative explanation of the possible consequences of CRBD. The control group received normal saline 2 ml, whereas the diphenhydramine group received diphenhydramine 30 mg intravenously after induction of general anesthesia. Then, all patients were catheterized with a 14F Foley catheter and the balloon was inflated with 10 ml of distilled water. All patients who complained of CRBD in the postoperative room were appeased with nursing. Ketorolac 30 mg was used as the rescue drug on patients' request or when the patient was evaluated as having moderate or severe CRBD. Bladder discomfort and its severity were assessed at 1, 2 and 6 h postoperatively. The severity of CRBD was graded as none, mild, moderate and severe. Adverse effects of diphenhydramine such as sedation, dry mouth or GI upset were recorded. Results: The incidence of CRBD was lower in the diphenhydramine group compared with the control group at 2 h (34.8 vs. 58.7%, p = 0.02) and 6 h (23.9 vs. 56.5%, p < 0.01) postoperatively. Diphenhydramine treatment also reduced the severity of CRBD at 6 h postoperatively (p = 0.01). Moreover, the request for rescue for CRBD was lower in diphenhydramine group at 2 h (8.7 vs. 26.1%, p = 0.03). There were no significant differences in side effects, such as sedation, dry mouth or gastrointestinal upset between the two groups (p > 0.05). Conclusion: Prophylactic diphenhydramine 30 mg at induction of general anesthesia reduced the incidence and severity of postoperative bladder discomfort without significant side effects in patients receiving gynecologic laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Purpose: Insomnia is highly prevalent in older persons and significantly impacts quality of life, functional abilities, and health status. It is frequently treated with benzodiazepines or Z-drugs. Due to adverse events, an increased use of alternative sedative medications has been observed in older adults. We aimed to study the efficacy and safety of alternative sedative medications for treating insomnia in older people, excluding benzodiazepines and Z-drugs. Methods: We conducted a systematic search of MEDLINE (PubMed), EMBASE, and the Cochrane Central register of Controlled Trials databases. We included randomized controlled trials and prospective and retrospective quasi-experimental studies, conducted in patients older than 65 years, without psychiatric or neurological comorbidities. Results: The systematic search yielded 9483 articles, of which 24 were included in this review, describing nine different sleep medications in total. No clear beneficial impact on sleep could be demonstrated in studies investigating the impact of melatonin (n = 10), paroxetine (n = 1), diphenhydramine (n = 1), tiagabine (n = 2), and valerian (n = 1). Ramelteon slightly improved sleep latency (n = 4), while doxepin was found to provide a sustained sleep improvement with a safety profile that was comparable to placebo (n = 3). Suvorexant showed an improved sleep maintenance with only mild side effects (n = 1). One study detected increased adverse effects of trazodone after 3 months but did not evaluate the effect on sleep. Conclusions: The overall level of evidence was limited, making it difficult to draw robust conclusions. Preliminary evidence points towards suvorexant, doxepin, and possibly ramelteon as effective and safe pharmacological alternatives for treating insomnia in older adults. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 21-year-old man with deceased donor kidney transplant. Topics include symptoms resolved with intravenous fluids and supportive care and etiology being ultimately thought to be acute gastroenteritis; and treated for acute gastroenteritis with acetaminophen, ondansetron, sucralfate, and a solution of aluminum and magnesium hydroxide-diphenhydramine.

Abstract: Dissolution testing is a very significant tool that adds in vivo relevance to in vitro analytical data, thus providing a realistic in vitro/in vivo correlation. Dissolution profiling serves as a predictor of biological performance since the rate limiting step in the absorption of any drug is the rate of release from its pharmaceutical formulation. Being a routine procedure in quality control laboratories for initial approval process and scaling-up, the development of more and more eco-friendly methods for dissolution monitoring is considered as a worldwide trendy goal. In the present contribution, a comparison was highlighted between the two analytical techniques of utmost importance in acquisition of dissolution profiles: UV-spectrophotometry and HPLC-PDA focusing on the greenness of each one for further consolidation of the biowaiver concept. Both techniques were applied on the recently FDA-approved combination naproxen sodium (NAPR) and diphenhydramine hydrochloride (DIPH) formulated as Aleve pm® tablets. For the first time, this binary mixture was analyzed by three UV-spectrophotometric methods. NAPR was directly determined by zero-order spectrophotometry at 330 nm, where the spectrum of DIPH shows zero contribution. Whereas DIPH was determined by three simple methods exploiting the ratio spectra calculated using the spectrum of 20 µg/ml NAPR as a divisor. The first proposed method was ratio difference (RD), the second was ratio subtraction, and the last one was derivative ratio method. Being the simplest method, RD was the spectrophotometric method of choice that was applied in monitoring the dissolution of DIPH from Aleve pm® tablets. Although RD method has been widely described in many publications dealing with pharmaceutical analysis, it is the first article that opens a new horizon for RD method in the way of being a real-life application rather than only a method for determination. The second technique was a previously published HPLC-PDA, in which dissolution was then monitored by calculating the peak area of each component drug over time. Methods' validation was performed agreeing with the ICH guidelines. The advantages and challenges of each technique are discussed in a side-by-side comparison giving a key to recognize which one can positively influence environmental well-being.Graphical abstract: [ABSTRACT FROM AUTHOR]

Introduction: Diphenhydramine is a widely used first-generation histamine (H1) antagonist that can be obtained without prescription in many countries. Massive ingestions can result in severe toxicity and even death. We describe a case of diphenhydramine overdose leading to cardiac arrest, cardiopulmonary resuscitation (CPR), and extracorporeal membrane oxygenation (ECMO) cannulation for refractory ventricular fibrillation, a process we refer to as extracorporeal cardiopulmonary resuscitation (ECPR).Case Report: Responding to a call for altered mental status, emergency medical service (EMS) personnel found an unconscious and seizing 17-year-old male. He had reportedly developed generalized tonic-clonic seizures and dysrhythmias after ingesting approximately 800 25-mg diphenhydramine tablets. He was transferred to our pediatric intensive care unit (PICU) after stabilization at a local emergency center. After approximately 7 hours of clinical stability and normalization of cardiac rhythm, electrolytes, and acidosis, he developed renewed seizure activity and accelerated ventricular rhythm leading to hemodynamic collapse and cardiac arrest. He was cannulated for veno-arterial extracorporeal membrane oxygenation (VAECMO) with CPR in progress. A pharmacobezoar located in his stomach was presumed to be the cause of his biphasic clinical deterioration. After 5 days, the patient was successfully weaned from ECMO support. Ten days later, his convalescence continued in the step-down unit and was discharged with good functional outcome.Discussion: Significant ingestion of anticholinergic substances is often fatal. This case describes a favorable outcome after ECPR and aggressive supportive management following a large intentional overdose of diphenhydramine. [ABSTRACT FROM AUTHOR]

1,6-Diphenyl-1,3,5-hexatriene is one of the most used fluorescent labels in cell membrane fluidity studies. However, its solubility in aqueous biological media is low and an initial solubilizing step is necessary. In this study, the authors present spectroscopic and computational results in order to explain the striking displacement observed in electronic spectra (absorption and fluorescence) in different solvents. The experimental results were correlated with those obtained by molecular dynamics simulations of multicomponent solutions, which revealed non-homogenous microscopic regions formation in the ternary aqueous DPH solutions. [ABSTRACT FROM AUTHOR]

Chronic insomnia affects 57% of the elderly in the United States, with impairment of quality of life, function, and health. Chronic insomnia burdens society with billions of dollars in direct and indirect costs of care. The main modalities in the treatment of insomnia in the elderly are psychological/behavioral therapies, pharmacological treatment, or a combination of both. Various specialty societies view psychological/behavioral therapies as the initial treatment intervention. Pharmacotherapy plays an adjunctive role when insomnia symptoms persist or when patients are unable to pursue cognitive behavioral therapies. Current drugs for insomnia fall into different classes: orexin agonists, histamine receptor antagonists, non-benzodiazepine gamma aminobutyric acid receptor agonists, and benzodiazepines. This review focuses on Food and Drug Administration (FDA)-approved drugs for insomnia, including suvorexant, low-dose doxepin, Z-drugs (eszopiclone, zolpidem, zaleplon), benzodiazepines (triazolam, temazepam), and ramelteon. We review the indications, dosing, efficacy, benefits, and harms of these drugs in the elderly, and discuss data on drugs that are commonly used off-label to treat insomnia, and those that are in clinical development. The choice of a hypnotic agent in the elderly is symptom-based. Ramelteon or short-acting Z-drugs can treat sleep-onset insomnia. Suvorexant or low-dose doxepin can improve sleep maintenance. Eszopiclone or zolpidem extended release can be utilized for both sleep onset and sleep maintenance. Low-dose zolpidem sublingual tablets or zaleplon can alleviate middle-of-the-night awakenings. Benzodiazepines should not be used routinely. Trazodone, a commonly used off-label drug for insomnia, improves sleep quality and sleep continuity but carries significant risks. Tiagabine, sometimes used off-label for insomnia, is not effective and should not be utilized. Non-FDA-approved hypnotic agents that are commonly used include melatonin, diphenhydramine, tryptophan, and valerian, despite limited data on benefits and harms. Melatonin slightly improves sleep onset and sleep duration, but product quality and efficacy may vary. Tryptophan decreases sleep onset in adults, but data in the elderly are not available. Valerian is relatively safe but has equivocal benefits on sleep quality. Phase II studies of dual orexin receptor antagonists (almorexant, lemborexant, and filorexant) have shown some improvement in sleep maintenance and sleep continuity. Piromelatine may improve sleep maintenance. Histamine receptor inverse agonists (APD-125, eplivanserin, and LY2624803) improve slow-wave sleep but, for various reasons, the drug companies withdrew their products. [ABSTRACT FROM AUTHOR]

Accurate, precise, and sensitive UPLC method was developed and validated for the simultaneous determination of a quaternary mixture containing guaiphenesin (GUP), oxeladin citrate (OXC), diphenhydramine (DPH), and sodium benzoate (SOB) in the presence of GUP-related substance, guaiacol (GUA). Chromatographic separation was achieved using NUCLEOSHELL® column—C18 (4.0 × 50.0 mm, 2.7 μm). Isocratic elution at a flow rate 1.0 mL/min was performed using a mobile phase consisting of acetonitrile:phosphate buffer pH 3.5 ± 0.1 (25.0:75.0, v/v). The specificity of the developed method was investigated by analyzing of laboratory-prepared mixtures containing different ratios of the four drugs, in the presence of GUA as well as their combined pharmaceutical formulation. The obtained results were statistically compared with those obtained by the official or reported methods, showing no significant difference with respect to accuracy and precision at p = 0.05. [ABSTRACT FROM AUTHOR]

Optimum conditions for the formation and extraction of a slightly soluble ion associate of diphenhydramine with the anionic complex molibydenum-gallein were determined. The ternary complex was extracted with butanol at pH 4-7. In the presence of diphenhydramine, the color strength became stronger, which was manifested in the absorption spectra as hypsochromic and bathochromic shifts. Some physicochemical characteristics of the complex were determined, the specificity of the reaction with respect to diphenhydramine was studied, and the probable complexation scheme was proposed. It was found that the molybdenum-gallein-diphenhydramine complex forms at a component ratio of 1: 2: 2. A procedure for the extraction-photometric determination of diphenhydramine in injection solutions and tablets was developed (RSD = 15-20%). The linearity range of the calibration graph was 0.02-0.20 mg/mL. [ABSTRACT FROM AUTHOR]

Multi-walled carbon nanotubes are adsorptive materials that have potential for remediation of organic contaminants in water. Sediment elutriate exposures were undertaken with Ceriodaphnia dubia to compare the toxic effects of diphenhydramine in the presence and absence of sediment and multi-walled carbon nanotubes. In both sediment and solution-only treatments, addition of 0.318 mg/g of carbon nanotubes significantly decreased 48-h mortality relative to control, with a 78.7%-90.1% reduction in treatments with nanotube-amended sediment and 40.7%-53.3% reduction in nanotube-amended water exposures. The greatest degree of relative mortality reduction occurred in sediments containing higher levels of natural organic matter, indicating a potential additive effect. [ABSTRACT FROM AUTHOR]

Background The unintentional misuse of over-the-counter sleep aids among older adults is an important public health problem and a focus of Healthy People 2020. Accordingly, the 2015 Beers Criteria for Potentially Inappropriate Medication Use in Older Adults recommends that individuals 65 years or older avoid use of diphenhydramine and doxylamine; however, many over-the-counter sleep products contain these active ingredients. Objective To identify the proportion of older adults using an over-the-counter medication containing diphenhydramine or doxylamine, and compare their characteristics with older adults using an over-the-counter medication that does not contain these ingredients. Setting Study participants were recruited from the Community Registry of the Pittsburgh Claude D. Pepper Older Americans Independence Center. Method The study sample was taken from a larger survey of 1025 participants on sleep health and over-the-counter sleep medication use conducted from February to April 2015. A subset of 169 participants aged 65 and older reporting taking at least one over-the-counter product to improve sleep within the past 30 days (16.5%) were selected for our analysis on associations between participant characteristics and potentially inappropriate use of over-the-counter sleep medications. Main outcome measure The proportion and characteristics of older adults taking at least one over-the-counter medication containing diphenhydramine or doxylamine. Results Of the 223 over-the-counter sleep medications listed by participants, 115 (52%) contained diphenhydramine or doxylamine. Using the Beers Criteria, we found that more than half of participants (59%) had used a potentially inappropriate over-the-counter medication containing diphenhydramine or doxylamine to improve sleep within the past 30 days. Participants taking at least one diphenhydramine or doxylamine containing medication were less likely to be aware of any safety risks in taking over-the-counter sleep medications than participants not taking these products (38 vs 49%, p = 0.016). Conclusion A majority of older adults in a limited sample from the United States taking an over-the-counter medication to improve sleep are taking a product containing diphenhydramine or doxylamine, both of which are classified as potentially inappropriate for older adults. Awareness of the safety risks of over-the-counter medications and addressing conditions that impact sleep quality could be facilitated through consultation with pharmacists and other healthcare providers. [ABSTRACT FROM AUTHOR]