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Background: We intend to evaluate the effect of intraoperative diphenhydramine administration on incidence and severity of catheter related bladder discomfort (CRBD) and pain after percutaneous nephrolithotomy. Methods: In a double blind randomized clinical trial, adult male patients undergoing percutaneous nephrolithotomy were enrolled. They were randomized into two groups by a computerized digital random allocation method. Before anesthesia induction, group D (Diphenhydramine group) (n = 48) received 5 ml normal saline containing 0.5 mg/kg of diphenhydramine intravenously. In group C (Control group) (n = 48), 5 ml of normal saline was injected in the same manner. Induction and maintenance of anesthesia were identical in both groups. The incidence and severity of CRBD and postoperative pain were assessed at recovery room. Results: The incidence of CRBD was significantly lower in group D than in group C (14% vs. 63%, P=0.001). The severity of CRBD was milder in group D in comparison to group C (P

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]

Background: Diphenhydramine (DPH) is an antihistamine medication that in overdose can result in anticholinergic symptoms and serious complications, including arrhythmia and coma. We aimed to compare the value of various machine learning (ML) models, including light gradient boosting machine (LGBM), logistic regression (LR), and random forest (RF), in the outcome prediction of DPH poisoning. Materials and Methods: We used the National Poison Data System database and included all of the human exposures of DPH from January 01, 2017 to December 31, 2017, and excluded those cases with missing information, duplicated cases, and those who reported co-ingestion. Data were split into training and test datasets, and three ML models were compared. We developed confusion matrices for each, and standard performance metrics were calculated. Results: Our study population included 53,761 patients with DPH exposure. The most common reasons for exposure, outcome, chronicity of exposure, and formulation were captured. Our results showed that the average precision-recall area under the curve (AUC) of 0.84. LGBM and RF had the highest performance (average AUC of 0.91), followed by LR (average AUC of 0.90). The specificity of the models was 87.0% in the testing groups. The precision of models was 75.0%. Recall (sensitivity) of models ranged between 73% and 75% with an F1 score of 75.0%. The overall accuracy of LGBM, LR, and RF models in the test dataset was 74.8%, 74.0%, and 75.1%, respectively. In total, just 1.1% of patients (mostly those with major outcomes) received physostigmine. Conclusion: Our study demonstrates the application of ML in the prediction of DPH poisoning. [ABSTRACT FROM AUTHOR]

Cough is a natural response from the respiratory tract by increasing the clearance of secretions and particles from mucus, irritants, foreign particles, and microbes, so that it can act as a body defense. One way that can be done to relieve cough symptoms is to use symptomatic drugs. Diphenhydramine HCl is an antihistamine that belongs to the first generation H1 receptor antagonist (H1 blocker) group which has sedative and anti-allergic properties. Diphenhydramine HCl is used to treat sneeze, runny nose, watery eyes, itches, skin rashes, and other cold symptoms or other allergies. Diphenhydramine HCl is also used to treat motion sickness and to induce sleep. The purpose of this study was to determine the contents of diphenhydramine HCl syrup sold in the market. This test uses the High Performance Liquid Chromatography (HPLC) method with acetonitrile as a mobile phase; water; triethylamine (50;50;0.5). The results obtained the average content of Diphenhydramine HCl 102.5%. So it can be concluded that the cough medicine sample meets the requirements because the contents are not less than 90% and not more than 110% based on the Indonesian Pharmacopoeia Edition VI 2020. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 60-year-old man with chronic spinal cord injury experiencing severe headaches, highlighting the differential diagnosis process and the eventual diagnosis of pituitary apoplexy. Topics include differential diagnoses for headaches in spinal cord injury patients, the importance of considering secondary causes such as pituitary adenomas, and the management approach for pituitary apoplexy involving neurosurgical consultation and hormone replacement therapy.

Drug monitoring is crucial for providing accurate and effective care; however, current methods (e.g., blood draws) are inconvenient and unpleasant. We aim to develop a non-invasive method for the detection and monitoring of drugs via human skin. The initial development toward this aim required information about which drugs, taken orally, can be detected via the skin. Untargeted liquid chromatography-mass spectrometry (LC-MS) was used as it was unclear if drugs, known drug metabolites, or other transformation products were detectable. In accomplishing our aim, we analyzed samples obtained by swabbing the skin of 15 kidney transplant recipients in five locations (forehead, nasolabial area, axillary, backhand, and palm), bilaterally, on two different clinical visits. Untargeted LC-MS data were processed using molecular networking via the Global Natural Products Social Molecular Networking platform. Herein, we report the qualitative detection and location of drugs and drug metabolites. For example, escitalopram/citalopram and diphenhydramine, taken orally, were detected in forehead, nasolabial, and hand samples, whereas N-acetyl-sulfamethoxazole, a drug metabolite, was detected in axillary samples. In addition, chemicals associated with environmental exposure were also detected from the skin, which provides insight into the multifaceted chemical influences on our health. The proof-of-concept results presented support the finding that the LC-MS and data analysis methodology is currently capable of the qualitative assessment of the presence of drugs directly via human skin.

Abstract 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. Graphical Abstract

Introduction: Diphenhydramine, either alone or in combination with pain relievers, is one of the widely used over-the-counter sleep aids. However, few studies have evaluated the use of diphenhydramine-containing products, such as Panadol Night, in Saudi Arabia. Therefore, the objectives of this study were to assess the prevalence of Panadol Night use and to identify factors associated with its use in the Eastern Province of Saudi Arabia. Methods: A cross-sectional study was conducted among adults aged 18 years or older in the Eastern Province of Saudi Arabia. Data were collected through an online self-administered questionnaire from 05 March 2022 to 20 March 2022. Chi-square tests and multivariable logistic regression models were used to examine the associations between Panadol Night use in the past month and independent variables. Results: A total of 1244 adults participated in the survey. Approximately, 42.3% reported that they have used Panadol Night in their lifetime; 12.1% used Panadol Night in the past month. The majority of the Panadol Night users (62.4%) reported that their use was based on their family/friends’ recommendations, while 23.6% used Panadol Night based on healthcare providers’ recommendations. The multivariable logistic regression models showed that gender, health related fields, perceived safety and effectiveness of Panadol Night, a history of insomnia, trouble sleeping due to pain, and sleep quality were significantly associated with the use of Panadol Night in the past month. Conclusions: Our findings indicated that adults’ perceptions of the effectiveness and safety of Panadol Night were significantly associated with its use. Also, adults in non-health related fields were more likely to use Panadol Night compared to those in health related fields. This suggests the need for raising awareness about the appropriate use of Panadol Night. Community pharmacists can play an essential role in educating patients during the time of purchase.

Exposures to hydroxyzine, a first-generation H1 antihistamine, have increased rapidly over the last two decades. Many assumptions about hydroxyzine poisoning are based on other antihistamines, like diphenhydramine. However, the receptor affinities of hydroxazine suggest that there should be fewer antimuscarinic findings than diphenhydramine. This was a cohort study that compared hydroxyzine and diphenhydramine exposures reported to the National Poison Data System between January 1, 2000, and December 31, 2020, and the Toxicologic Investigators Consortium Core Registry between January 1, 2010, and December 31, 2020. The primary outcome was to assess for antimuscarinic findings in hydroxyzine-poisoned patients, using diphenhydramine-poisoned patients as a comparison group. The secondary outcomes were to assess for markers of overall toxicity. Inclusion criteria were single-substance exposures with known outcomes. Exclusion criteria for National Poison Data System exposures were chronic exposures, unintentional exposures, and patients younger than 12 years old. There were no exclusion criteria for exposures reported to the Toxicologic Investigators Consortium Core Registry. There were 17,265 hydroxyzine and 102,354 diphenhydramine exposures reported to the National Poison Data System and 134 hydroxyzine and 1,484 diphenhydramine exposures reported to the Toxicologic Investigators Consortium Core Registry that met inclusion criteria. In both datasets, hydroxyzine-poisoned patients had lower rates and relative risk of developing antimuscarinic findings or receiving physostigmine, with the exception of hyperthermia in the Toxicologic Investigators Consortium Core Registry dataset. Coma/central nervous system depression (major), respiratory depression, seizures, ventricular dysrhythmias, intubation, and benzodiazepine administration were less likely in hydroxyzine-poisoned patients, but central nervous system depression (mild) was more likely in exposures reported to the National Poison Data System. The mortality in hydroxyzine-poisoned patients was rare: 0.02% and 0.8% of exposures reported to the National Poison Data System and Toxicologic Investigators Consortium Core Registry, respectively. The clinical manifestations of hydroxyzine exposures are consistent with the pharmacology of hydroxazine. The clinical effects were consistent across two United States national datasets. Clinicians should not generalize the illness script of diphenhydramine exposures to hydroxyzine exposures. Hydroxyzine-poisoned patients were less likely to develop antimuscarinic findings than diphenhydramine-poisoned patients. Hydroxyzine-poisoned patients were more likely to have mild central nervous system depression than an antimuscarinic toxidrome. [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]

Background: Peritoneal adhesion formation is an inevitable consequence of abnormal repair of the peritoneum following different peritoneal injuries of intra-abdominal operations with the subsequent morbidity that they represent. Vast efforts have been made to elucidate the cause and prevent the development of abdominal adhesions. The aim of our study is to compare the capability of colchicine versus diphenhydramine (DPH) and methylprednisolone (MP), and also prednisolone in adhesion prevention. Methods: Sixty-one male Wistar stock rats were divided into four groups. The first group attended as the control group. Groups 2, 3, and 4 received oral combination of MP + DPH solution (20 mg/kg), colchicine (0.02 mg/kg), and prednisolone (1 mg/ kg), respectively. Adhesion bands were induced by standardized abrasion of the peritoneum through a midline laparotomy. All rats were sacrificed on the 15th-day post medication administration and the subjects underwent an exploratory laparotomy. The presence of adhesions was evaluated with the modified using Nair's classification. Results: The proportion of the control group with substantial adhesion bands (73.3%) was significantly higher than that of the MP + DPH (13.3%), colchicine (33.3%), and prednisolone (31.3%) groups. There were significant differences between the scores of the control and the MP + DPH, colchicine, and prednisolone groups (P = 0.001, 0.028, and 0.019, respectively). There was no statistically significant difference to favor colchicine against MP + DPH (P = 0.390) or MP + DPH against prednisolone (P = 0.394). Conclusions: Both colchicine and combination of DPH + MP prevented postoperative abdominal adhesions separately in our study. However, the lowest adhesion formation rate was observed in the DPH + MP group, even lower than the prednisolone group. [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]

The aim of the present study was to formulate chitosan-coated alginate nanoparticles containing the drug diphenhydramine hydrochloride (DHH). Diphenhydramine hydrochloride (DHH) is the prototype of H1-antihistaminic drugs. It is a lipophilic drug, that easily crosses the blood–brain barrier when taken orally causing decrements in alertness and performance. Multiple applications of topical drug products are required. Thus, drug incorporation in nanocarriers would increase the skin penetration powers increasing the drug efficacy. Chitosan-coated alginate (CCA) nanoparticles were prepared via polyelectrolyte complex technique adopting 23 full factorial designs. Three factors, namely, alginate concentration, drug-to-alginate ratio and CaCl2 volume, each in two levels were studied. The prepared formulae were evaluated utilizing entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and in vitro release. The characterization process was then followed by optimization. At alginate conc. of 1%, drug to alginate ratio of 2:1 and CaCl2 volume of 4 mL, NP8 was chosen as a candidate formula. Histopathological examination on shaved rat dorsal skin disclosed the safety of NP8 with no signs of necrosis or even inflammation. The enhanced topical delivery of diphenhydramine hydrochloride enclosed in the developed nanoparticles was further proved by induction of allergic reaction using intradermal histamine injection. The results revealed the superior ability of NP8 to decrease the diameter of the formed wheal in comparison to the marketed DHH product. Thus, CCA nanoparticles are considered candidate nanocarriers for fortifying the topical antihistaminic activity of DHH. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this systematic review is to assess the efficacy and safety of hydroxyzine for insomnia in adults. Methods: A comprehensive literature search of PubMed, Embase, and CENTRAL databases was conducted to identify relevant published studies through October 2022 using the search terms: hydroxyzine and sleep, insomnia, sleep disorder or sleep initiation and maintenance disorders. Studies identified for review included prospective, interventional designs or cohort trials that reported impact of hydroxyzine on sleep in adults. Animal studies, case reports, non‐English articles, letters to the editor, case studies, and conference abstracts were excluded. Data were extracted using a standardized systematic process. Results: Five articles were identified for inclusion, including 1 open‐label and 4 randomized controlled trials, evaluating a total of 207 patients receiving hydroxyzine 25 mg, 50 mg, or 100 mg at bedtime. Mixed efficacy was demonstrated in the sleep measures of sleep onset, sleep maintenance, and sleep quality. The most common adverse drug effect was dry mouth, although 4 of the 5 studies did not report safety outcomes. Conclusions: The studies in this review suggest hydroxyzine could be considered as a short‐term treatment option for adults with insomnia for whom previous therapy was ineffective, not tolerated, or contraindicated. Additional long‐term studies with an active comparator are needed to further establish its role in insomnia treatment. [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]

Objective: Pain after surgery is one of the risk factors of postoperative nausea and vomiting (PONV) and increased recovery complications due to the mechanisms it causes. Histamine blockers with their effects (sedation, reduction of pain and anxiety) may lead to reduction of recovery complications; Therefore, the present study was conducted with the aim of the effect of pretreatment with diphenhydramine on recovery complications in minor ear, nose, and throat surgeries. Materials and Methods: 100 patients' candidates for minor ENT surgeries were included in this double-blind randomized clinical trial study as available sampling. Ten minutes before the induction of anesthesia, 2 cc of diphenhydramine (25 mg) were injected into the patients of the intervention group and 2 cc of normal saline were injected into the patients of the control group; Pain intensity and PONV in recovery and 2, 4, 8, 10, 12, 24 hours after discharge from recovery were compared between two groups using Independent-Samples T-Test. Results: In recovery, the incidence of nausea and vomiting (p=0.02) and the need for ondansetron in the diphenhydramine group were significantly lower than the control group (p=0.05). On the other hand, the incidence of nausea and vomiting in the 24-hour evaluation was significantly lower in the diphenhydramine group than in the control group; The average total injected ondansetron during 24 hours in the intervention group (4.41±0.17) was significantly (P=0.031) lower than the control group (9.37±1.41). Conclusion: Prophylactic injection of diphenhydramine leads to reduction of recovery complications (short term) after anesthesia in limited ENT surgeries. [ABSTRACT FROM AUTHOR]

Aim: To evaluate retrospectively the safety and technical success of subcutaneous diphenhydramine as an alternative local anaesthetic for radiology procedures.Materials and Methods: Between January 2000 and April 2021, 84 image-guided procedures were performed in 81 adult patients (mean age 61 years, 86% female) using 1% injectable diphenhydramine as a local anaesthetic. Indications were history of severe allergy to "-caine" local anaesthetics in 76 (90%) patients and recent administration of bupivacaine liposomal injectable suspension in eight (10%) patients. Twelve of the 84 (14%) procedures were performed with concomitant moderate sedation. Patient characteristics, procedural techniques, and clinical outcomes were reviewed. Early and delayed (30-day) complications were classified as either related to local diphenhydramine injection or to the procedure itself. Procedure-related complications were gradated using the Clavien-Dindo system.Results: Percutaneous biopsy was the most frequently performed procedure (57/84, 67%). Fifty-nine (70%) of the 84 procedures were ultrasound guided. The most common procedural site was the breast (34/84, 40%). All procedures were technically successful. There were two minor injection-related complications related to post-procedural pain. A single minor procedure-related complication involved a patient requiring hospital admission for post-renal biopsy related haematuria.Conclusion: Injectable diphenhydramine appears to be a safe and effective local anaesthetic alternative in patients with "-caine" class contraindications undergoing radiology procedures. A future prospective trial would be useful to assess the safety profile in an large cohort of patients. [ABSTRACT FROM AUTHOR]

La difenhidramina tiene efectos antihistamínico anti-H1 específico y antimuscarínico que pueden ocasionar un desenlace fatal según la dosis total ingerida. Se reporta un caso de intoxicación por difenhidramina tratado de forma exitosa con emulsiones lipídicas a pesar de ingesta de dosis letal. Se presenta el caso de un paciente de 19 años que ingresó por intoxicación por difenhidramina a dosis de 25 mg/kg (1.5 g) después del tiempo de descontaminación, con toxidrome anticolinérgico, con neurotoxicidad, cardiotoxicidad (QRS y QT prolongados) y sin respuesta al enfoque inicial, se iniciaron emulsiones lipídicas y, a su vez, se logró alta temprana por evolución clínica favorable y resolución de la prolongación del intervalo QTc y del cuadro anticolinérgico. La emulsión lipídica es una opción terapéutica para disminuir la morbimortalidad y la estancia hospitalaria por contrarrestar la cardiotoxicidad y neurotoxicidad producidas por moléculas lipofílicas como la difenhidramina.

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]

TikTok™, a social media platform popular with teenagers and young adults, hosts a variety of short‐form user videos with durations from 15 s to 10 min. Among these videos are potentially dangerous "challenges," such as the "Skull Breaker" challenge and the "Benadryl" challenge. Benadryl (diphenhydramine) is an over‐the‐counter medication with potential for misuse in both suicidal and recreational purposes. We report the case of a 14‐year‐old girl who reportedly ingested an unknown amount of diphenhydramine while taking part in a TikTok™ social media challenge. Autopsy revealed marked bilateral pulmonary congestion and edema, as well as a bright pink granular material within the esophagus, stomach, duodenum, and proximal jejunum. A postmortem femoral blood sample result identified a lethal blood concentration of diphenhydramine (49,658 ng/ml). Physicians and other healthcare providers need to be aware of social media trends that may pose public health threats. Teenagers are a particularly susceptible group and need to be informed of the risks associated with these "challenges." For the forensics field, a knowledge of and process for accessing social media platforms can be critical for investigating deaths. Given the extremely elevated concentration of diphenhydramine in this case, a knowledge of circumstances of death, the scene, and social media trends can assist the forensic pathologist in determining the correct manner of death—accident versus suicide. [ABSTRACT FROM AUTHOR]

Background and Aim: Diphenhydramine is an H1-antihistamine that counteracts the toxic effects of organophosphate and carbamate insecticides that inhibit cholinesterase (ChE) activity. This meta-analysis aimed to investigate the effects of diphenhydramine on ChE inhibition induced by these insecticides in the plasma, erythrocytes, or whole brain of experimental animals. Materials and Methods: A data search was performed on erythrocyte, plasma, and brain ChE inhibition caused by organophosphate and carbamate insecticides in experimental animals (mice, rats, and chicks) treated with the antihistamine diphenhydramine in accordance with preferred reporting items for systematic reviews and meta-analysis, which was done by the two-group random-effects model meta-analysis. The meta-analysis included 18 records extracted from six studies that appeared from 1996 to 2022. Results: Using the random-effects model, a two-group meta-analysis revealed that the combined effect size (ChE inhibition) was significantly more favorable in the control group than in the diphenhydramine intervention, as shown by a forest plot. The combined effect size (standardized mean difference) was 0.67, with a standard error of 0.3, a lower limit of 0.04, and an upper limit of 1.29 (p = 0.025). The heterogeneity was moderate, as I2 of the combined effect size was 74%, with a significant Cochrane Q-test result (Q = 65, p < 0.0001). Subgroup analysis indicated that, with brain ChE inhibition, the heterogeneity (I2) became 5%, which was lower than ChE inhibition in plasma (84%) and erythrocytes (78%). No publication bias was identified using the funnel plot and Egger's test. Conclusion: This meta-analysis suggests that, in addition to its documented antidotal action against ChE-inhibiting insecticides, diphenhydramine can also reduce the extent of ChE inhibition, especially in the brain, which is the main site of toxicity of these insecticides. There is a need for additional studies to assess such enzyme inhibition in different parts of the brain. [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]

Objectives: Adjunct therapy with anticholinergic agents has been proposed to reduce the incidence of extrapyramidal side effects such as akathisia following treatment with neuroleptics or metoclopramide. This systematic review assessed the effectiveness of anticholinergic agents to prevent neuroleptic or metoclopramide‐induced akathisia in patients presenting to the emergency department (ED) with benign headache. Methods: Eight electronic databases and the gray literature were searched to identify randomized controlled trials involving adult patients presenting to the ED with primary headache treated with neuroleptic or metoclopramide. Study selection, data extraction, and quality assessment were completed by two independent reviewers. Individual or pooled meta‐analysis of dichotomous outcomes were calculated as relative risks (RRs) with 95% confidence intervals (CIs) using a random‐effects model. Heterogeneity was assessed using the I2 statistic. Results: A total of 1032 studies were screened, of which two studies were included in the review. Both studies provided patients with diphenhydramine following treatment with neuroleptics or metoclopramide. Treatment with diphenhydramine did not reduce the incidence of akathisia compared to treatment with placebo (RR 0.83, 95% CI 0.43–1.61, I2 = 0%). The impact of diphenhydramine on pain relief, need for rescue medications, and relief of other extrapyramidal side effects was reported in one of the two studies, with no significant differences noted in any outcomes compared to patients treated with placebo. Conclusion: This review found insufficient evidence to recommend the use of diphenhydramine as an adjunct therapy to prevent akathisia in ED patients treated with neuroleptics or metoclopramide for primary headache. This finding relies on the results of two small randomized controlled trials with incomplete outcome reporting. Additional high‐quality studies are needed to better understand the clinical efficacy of agents with anticholinergic properties in the ED management of patients with primary headaches. [ABSTRACT FROM AUTHOR]

The chemical stability of diphenhydramine (DIPH), azelastine (AZE) and bepotastine (BEPO) was examined in solutions and solids. The drugs were subjected to high temperature (70 °C for 35 h) or UV/VIS light (18.902–94.510 kJ/m2) at pH 1–13, to examine their percentage degradation and kinetics of degradation. Further, the stability of solid DIPH, AZE and BEPO was examined in the presence of excipients of different reactivity, i.e., citric acid (CA) and polyvinyl alcohol (PVA) under high temperature/high humidity (70 °C/80% RH) or UV/VIS light (94.510 kJ/m2). Under high temperature, DIPH degraded visibly (>19%) at pH 1 and 4, AZE was shown stable, while the degradation of BEPO was rather high (>17%) in all pH conditions. Under UV/VIS irradiation all the drugs were shown labile with degradation in the range 5.5–96.3%. As far as the solid mixtures were concerned, all drugs interacted with excipients, especially under high temperature/high humidity or UV/VIS light. As a result, DIPH, AZE and BEPO were compared in terms of their stability, with regard to their different structures and acid/base properties. All these results may be helpful for manufacturing, storing and applying these drugs in their topical (skin, nasal and ocular), oral and injectable formulations. [ABSTRACT FROM AUTHOR]

Objective: Considering that nausea and vomiting are very common after laparoscopic cholecystectomy surgery, it is important to take preventive measures. Also, no method has been able to completely prevent nausea and vomiting after surgery; In this study, the effects of two drugs granisetron (as a specific inhibitor of 5HT-3 receptor) and diphenhydramine (as an antihistamine) were evaluated. Materials and Methods: In this one-blind clinical trial that was conducted in 2019 with the participation of patients who were candidates for elective laparoscopic cholecystectomy surgery (120 patients), the patients were randomly divided into two groups. Patients in the granisetron group received 3 mg of this drug 15 minutes before extubation, and patients in the diphenhydramine group received 50 mg of this drug intravenously 15 minutes before extubation. The intensity of pain, intensity of nausea and vomiting, occurrence of nausea and vomiting, dose of netoclopramide and opioid were compared between two groups. Results: The average ± standard deviation of the severity of nausea and vomiting at all measured times in the granisetron group was insignificantly lower than the diphenhydramine group (P<0.05), also the need for metoclopramide was always lower in the granisetron group. It was less than the group receiving diphenhydramine (P<0.05); On the other hand, the pain intensity at all times in the group receiving granisetron was insignificantly lower than the group receiving diphenhydramine (P<0.05). Conclusion: Granisetron slightly reduces nausea and vomiting, the need for metoclopramide, and pain intensity after laparoscopic cholecystectomy compared to diphenhydramine. [ABSTRACT FROM AUTHOR]