Diphenhydramine 14mg/5ml / Levomenthol 2mg/5ml oral solution

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 licence: CC BY

Nanoplastics (NPLs) became ubiquitous in the environment, from the air we breathe to the food we eat. One of the main concerns about the NPLs risks is their role as carrier of other environmental contaminants, potentially increasing their uptake, bioaccumulation and toxicity to the organisms. Therefore, the main aim of this study was to understand how the presence of polystyrene NPLs (∅ 44 nm) will influence the toxicity (synergism, additivity or antagonism) of the antihistamine diphenhydramine (DPH), towards zebrafish (Danio rerio) embryos, when in dual mixtures. After 96 hours (h) exposure, at the organismal level, NPLs (0.015 or 1.5 mg/L) + DPH (10 mg/L) induced embryo mortality (90%) and malformations (100%) and decreased hatching (80%) and heartbeat rates (60%). After 120 h exposure, NPLs (0.015 or 1.5 mg/L) + DPH (0.01 mg/L) decreased larvae swimming distance (30-40%). At the biochemical level, increased glutathione S-transferases (55-122%) and cholinesterase (182-343%) activities were found after 96 h exposure to NPLs (0.015 or 1.5 mg/L) + DPH (0.01 mg/L). However, catalase (CAT) activity remained similar to the control group in the mixtures, inhibiting the effects detected after the exposure to 1.5 mg/L NPLs alone (increased 230% of CAT activity). In general, the effects of dual combination - NPLs + DPH (even at concentrations as low as 10 μg/L of DPH) - were more harmful than the correspondent individual exposures, showing the synergistic interactions of the dual mixture and answering to the main question of this work. The obtained results, namely the altered toxicity patterns of NPLs + DPH compared with the individual exposures, show the importance of an environmental risk assessment considering NPLs as a co-contaminant due to the potential NPLs role as vector for other contaminants.

Abstract licence: CC BY

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 licence: CC BY-NC-SA

Background: The urine immunochromatographic assay is a useful screening tool for patients suspected of acute drug intoxication in emergency conditions. Diphenhydramine intoxication shows symptoms similar to those of tricyclic antidepressant (TCA) intoxication. Case presentation: We examined a case of diphenhydramine intoxication showing cerebellar ataxia and prolonged false positive results for TCA in the urine. The urine TCA test showed persistently positive results even 60 h after the patient's initial drug screening. We observed negative conversion 90 h after the initial drug screening. Discussion: Considering the similarities of clinical symptoms between diphenhydramine and TCA intoxication, emergency physicians should consider the possibility of cross-reactivity in the diagnosis of a patient with unknown acute drug intoxication showing positive results of TCA immunochromatographic assay in the urine. Conclusion: The present case suggests that diphenhydramine overdose may cause cerebellar ataxia and show prolonged cross-reactivity as TCA in the urine.

Abstract licence: CC BY

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Abstract licence: CC BY