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1.
Sci Total Environ ; 855: 158982, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36155033

RESUMO

With rapid economic development, an increasing number of people suffer from mental health diseases, which are gradually receiving the attention of society. However, basic data from surveys of mental disorders are limited. Composite influent samples were collected from 26 wastewater treatment plants in 23 major cities in China. The concentrations of the psychoactive drugs diphenhydramine, fluoxetine, doxepin, imipramine, sulpiride, zolpidem, carbamazepine, and flunitrazepam in the wastewater were determined. The detection frequency of diphenhydramine, sulpiride, and carbamazepine was close to 100 %, whereas that of the compounds was lower than 35 %. Carbamazepine had the highest mean consumption (31.1 mg/d/1000 people), followed by diphenhydramine (10.4 mg/d/1000 people) and sulpiride (11.3 mg/d/1000 people). Wastewater-based epidemiology (WBE) estimates of the average use of the three drugs were lower than those from the drug statistics data. Consumption of diphenhydramine in northern China was higher than that in southern China. A correlation analysis of psychotropic and illicit drugs revealed a correlation between sulpiride and heroin use, which may be related to the adverse effects of sulpiride treatment after heroin withdrawal. Psychotropic drug use is associated with both economic and social factors. We found associations between the use of the three drugs and age, occupation, and obesity, which are risk factors for mental disorders. The results showed that the monitoring of psychotropic drug using WBE has a certain reference value for public health care and for improving the understanding of mental disorders.


Assuntos
Vigilância Epidemiológica Baseada em Águas Residuárias , Poluentes Químicos da Água , Humanos , Cidades , Heroína/análise , Sulpirida/análise , Poluentes Químicos da Água/análise , Águas Residuárias/análise , Psicotrópicos/análise , China/epidemiologia , Carbamazepina/análise , Difenidramina/análise
2.
Pan Afr Med J ; 42: 289, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405657

RESUMO

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


Assuntos
Distonia , Hipersensibilidade , Feminino , Humanos , Distonia/induzido quimicamente , Distonia/diagnóstico , Difenidramina/efeitos adversos
3.
Tokai J Exp Clin Med ; 47(4): 170-176, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36420548

RESUMO

BACKGROUND: To date, topical allergic rhinitis drugs must be applied intranasally. We studied the efficacy, safety, and impact on co-existing asthma symptoms of transdermal delivery of diphenhydramine through the nasal ala. METHODS: We enrolled outpatients with symptomatic allergic rhinitis and asthma who were on stable medication for at least 4 weeks. Patients applied diphenhydramine ointment, 0.07 g measured with weighing spoon (0.7 mg diphenhydramine), to the nasal ala twice a day for 2 weeks, followed by 2 weeks' washout. Effects were assessed with the Japanese Allergic Rhinitis Standard Quality of Life Questionnaire (JRQLQ) and Self-assessment of Allergic Rhinitis and Asthma (SACRA) and Asthma Control Test (ACT) questionnaires. RESULTS: Ten patients participated in the study. Two patients experienced acute exacerbation of asthma during the intervention phase, but no other adverse effects occurred. Self-assessments indicated efficacy in treating nasal symptoms in 5 patients. No significant changes in scores were seen, although mean total JRQLQ score showed a numerical improvement (from 34.3 [21.0] to 14.4 [8.8]; P = 0.0547). Asthma symptoms improved subjectively in 2 patients. CONCLUSIONS: The efficacy of transdermal application of diphenhydramine on the nasal ala for treating allergic rhinitis was not conclusive, but appears to be effective in certain patients.


Assuntos
Asma , Qualidade de Vida , Humanos , Projetos Piloto , Difenidramina/uso terapêutico , Asma/tratamento farmacológico , Inquéritos e Questionários
4.
Farm Hosp ; 46(3): 146-151, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-36183207

RESUMO

OBJECTIVE: To estimate the incidence of potential in-hospital adverse reactions  with the use of alert drugs in a general hospital in southern Brazil. Method: Cross-sectional study, carried out in a hospital in southern Brazil. The  electronic medical records (TASY®) of patients hospitalized between January  and August 2020, who were prescribed one of the drugs earmarked for  tracking adverse drug reactions, were evaluated: the drugs included  flumazenil, fexofenadine hydrochloride, naloxone, promethazine, diphenhydramine and loperamide. RESULTS: A total of 13,476 medical records were reviewed and 204 (1.5%)  were included in the study in which tracker use was indicated in the management of adverse drug reactions. In this study a total of 18 different signs or symptoms were found in medical records, with  pruritus/hyperemia/urticaria being the most reported symptoms (n = 76).  Among the drug classes that caused most adverse drug reactions, opioids were  the most mentioned (n = 44). It should be noted that in 49 medical  records the information on which drug caused the adverse events was not  reported. Regarding the cause of hospitalization of patients who used  creening drugs, cancer was the most frequent (n = 37). CONCLUSIONS: This study indicates that the use of trackers can be a tool to  estimate the occurrence of adverse drug reactions and to establish adverse  events related to the use of medications, which should be reported to the  pharmacovigilance service, with a view to patient safety.


OBJETIVO: Estimar la incidencia de potenciales reacciones adversas intrahospitalarias con el uso de prescripciones alertantes en un  hospital general del sur de Brasil.Método: Estudio transversal, realizado en un hospital del sur de Brasil. Se  evaluaron las historias clínicas electrónicas (TASY®) de los pacientes hospitalizados entre enero y agosto de 2020, a los que se les  prescribió uno de los medicamentos destinados al seguimiento de reacciones  adversas a medicamentos: los medicamentos incluían flumazenil, clorhidrato de fexofenadina, naloxona, prometazina, difenhidramina y  loperamida. RESULTADOS: Se revisaron 13.476 historias clínicas y se incluyeron 204 (1,5%) en el estudio en el que se indicó el uso de prescripciones alertantes en  el manejo de reacciones adversas a medicamentos. En este estudio se  encontró un total de 18 signos o síntomas diferentes en las historias clínicas,  siendo el prurito, la hiperemia y la urticaria los síntomas más reportados (n =  76). Entre las clases de fármacos que causaron la mayoría de las reacciones  adversas a medicamentos, los opioides fueron los más mencionados (n = 44).  Cabe señalar que en 49 historias clínicas no se reportó la información sobre  qué fármaco causó los eventos adversos. En cuanto a la causa de  hospitalización de los pacientes que utilizaron prescripciones alertantes, el  cáncer fue la más frecuente (n = 37). Conclusiones: Este estudio indica que el uso de alertadores puede ser una  herramienta para estimar la incidencia de reacciones adversas a medicamentos y establecer eventos adversos relacionados con el uso de medicamentos, los cuales deben ser reportados al servicio de  armacovigilancia, con miras a la seguridad del paciente.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacovigilância , Sistemas de Notificação de Reações Adversas a Medicamentos , Estudos Transversais , Difenidramina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Flumazenil , Hospitais , Humanos , Loperamida , Naloxona , Prometazina
5.
Drug Discov Ther ; 16(5): 245-250, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36261390

RESUMO

Cetirizine, a second-generation antihistamine, and diphenhydramine, a first-generation antihistamine, are among the most widely used anti-allergic drugs. In addition to longer duration of action and less incidence of sedative side effects, recent clinical studies also indicate a higher potency of cetirizine than diphenhydramine in the treatment or prevention of allergic disorders. In the present study, using the differential-interference contrast (DIC) microscopy, we examined the effects of cetirizine and diphenhydramine (1 µM to 1 mM) on the degranulation from rat peritoneal mast cells. Using fluorescence imaging of a water-soluble dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. At relatively higher concentrations (100 µM, 1 mM), both cetirizine and diphenhydramine significantly reduced the numbers of degranulating mast cells. Of note, at 1 mM, cetirizine more markedly reduced the number than diphenhydramine, almost entirely suppressing the degranulation of mast cells. Additionally, 1 mM cetirizine and levocetirizine, another second-generation antihistamine, almost totally inhibited the process of exocytosis in mast cells and washed out the trapping of the lucifer yellow on the cell surface, while diphenhydramine and chlorpheniramine, another first-generation antihistamine, did not. This study provided in vitro evidence for the first time that cetirizine more potently inhibited the process of exocytosis in mast cells than diphenhydramine, indicating its higher potency as a mast cell-stabilizer. Such mast cell-stabilizing property of cetirizine could be ascribed to its counteracting effect on the plasma membrane deformation in degranulating mast cells.


Assuntos
Antialérgicos , Cetirizina , Ratos , Animais , Cetirizina/farmacologia , Difenidramina/efeitos adversos , Mastócitos , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Antialérgicos/farmacologia
6.
Basic Clin Pharmacol Toxicol ; 131(6): 566-574, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36181236

RESUMO

The primary aim of this pilot study was to develop a machine learning algorithm to predict and distinguish eight poisoning agents based on clinical symptoms. Data were used from the National Poison Data System from 2014 to 2018, for patients 0-89 years old with single-agent exposure to eight drugs or drug classes (acetaminophen, aspirin, benzodiazepines, bupropion, calcium channel blockers, diphenhydramine, lithium and sulfonylureas). Four classifier prediction models were applied to the data: logistic regression, LightGBM, XGBoost, and CatBoost. There were 201 031 cases used to develop and test the algorithms. Among the four models, accuracy ranged 77%-80%, with precision and F1 scores of 76%-80% and recall of 77%-78%. Overall specificity was 92% for all models. Accuracy was highest for identifying sulfonylureas, acetaminophen, benzodiazepines and diphenhydramine poisoning. F1 scores were highest for correctly classifying sulfonylureas, acetaminophen and benzodiazepine poisonings. Recall was highest for sulfonylureas, acetaminophen, and benzodiazepines, and lowest for bupropion. Specificity was >99% for models of sulfonylureas, calcium channel blockers, lithium and aspirin. For single-agent poisoning cases among the eight possible exposures, machine learning models based on clinical signs and symptoms moderately predicted the causal agent. CatBoost and LightGBM classifier models had the highest performance of those tested.


Assuntos
Intoxicação , Venenos , Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Centros de Controle de Intoxicações , Projetos Piloto , Acetaminofen , Bupropiona , Lítio , Bloqueadores dos Canais de Cálcio , Aprendizado de Máquina , Difenidramina , Benzodiazepinas , Aspirina , Intoxicação/diagnóstico
7.
J Midwifery Womens Health ; 67(5): 644-650, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36215142

RESUMO

During active labor, a birthing person with cervical edema often has a dysfunctional or prolonged labor and, therefore, an increased risk for cesarean birth. Midwives seeking evidence on how to manage cervical edema when they are faced with this clinical situation will note a gap in the literature regarding the management of cervical edema that this report aims to fill. This case will discuss the use of intravenous diphenhydramine (Benadryl), the application of ice to the cervix, side-lying release, epidural analgesia use, manual reduction of the cervix, and various positions to encourage reduction in cervical swelling. It is hoped these strategies will add to a midwife's clinical resources by providing ways to promote vaginal birth in the setting of cervical edema during labor.


Assuntos
Trabalho de Parto , Tocologia , Difenidramina , Edema , Feminino , Humanos , Gelo , Gravidez
8.
Chemosphere ; 308(Pt 2): 136382, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36088977

RESUMO

Diphenhydramine (DPH) is a pharmaceutical with multiple modes of action, primarily designed as an antihistamine therapeutic drug. Among antihistamines, DPH is a significant contaminant in the environment, frequently detected in surface waters, sediments, and tissues of aquatic biota. In the present study, signal crayfish Pacifastacus leniusculus was used as a model organism because of their prominent ecological roles in freshwater ecosystems. The biochemical effects were investigated in crayfish exposed to the environmental (low: 2 µg L-1), ten times elevated (medium: 20 µg L-1), and the sublethal (high: 200 µg L-1) nominal concentrations of DPH in water for 96 h. Lipid peroxidation, antioxidant enzyme activities, and acetylcholinesterase activity were assessed as toxicological biomarkers in crayfish hepatopancreas, gills, and muscles. Low and medium DPH exposure caused imbalances only in glutathione-like enzyme activities. Integrated biomarker response showed the absolute DPH toxicity effects on all tested tissues under high exposure. This study identified that high, short-term DPH exposure induced oxidative stress in crayfish on multiple tissue levels, with the most considerable extent in muscles.


Assuntos
Acetilcolinesterase , Astacoidea , Animais , Antioxidantes/farmacologia , Biomarcadores , Difenidramina/toxicidade , Ecossistema , Glutationa/farmacologia , Preparações Farmacêuticas , Água/farmacologia
9.
West Afr J Med ; 39(9): 928-934, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36126325

RESUMO

BACKGROUND AND OBJECTIVE: Cough from URTI is common, leads to discomfort, sleep loss and stress in caregivers, leading to use of ineffective and potentially harmful over-the-counter medications. Honey is cost-effective and safe for children above one year of age. It is readily available and is a potentially valuable demulcent for treatment of childhood cough. The study aimed to determine the effect of honey on cough frequency and severity among children with URTI in outpatient setting. METHODS: A single-blind randomised control trial involving children presenting with cough from URTI attending the GOPC of FMC Keffi. Eighty-four children presenting with cough from URTI were recruited, randomised into two groups of 42 and administered Honey (intervention) and Diphenhydramine (control) in three consecutive bedtime doses. Socio-demographic and clinical data including cough frequency, severity and impact on children and caregivers was collected using Paediatric Cough Questionnaire and Kingston Caregiver Stress Scale tool. Data was analysed using SPSS version 25. A p<0.05 was considered statistically significant. RESULTS: Majority (56.0%) of the participants were males, with a mean age +SD of 4±1.47 years. Median cough frequency score for intervention and control groups pre and post intervention decreased (5.00 and 0.00 vs 5.00 and 3.00, p<0.001). Median cough severity score decreased (4.00 and 0.00 vs 4.00 and 3.00, p<0.001), Post intervention pooled caregivers' burden significantly reduced, (5.00 and 11.00 for intervention and control respectively) and sleep pattern improved among children and caregivers (0.00, 2.00 p<0.001; and 0.00, 2.00 p<0.001, for children and caregivers respectively. CONCLUSION: Night-time honey doses given to children with cough from URTI significantly reduces symptoms and improves children and caregivers sleep compared to Diphenhydramine DPH.


CONTEXTE ET OBJECTIF: La toux due à l'URTI est courante, entraîne une gêne, une perte de sommeil et du stress chez les soignants, conduisant à l'utilisation de médicaments en vente libre inefficaces et potentiellement nocifs. Le miel est rentable et sans danger pour les enfants de plus d'un an. Il est facilement disponible et est un adoucissant potentiellement précieux pour le traitement de la toux infantile. L'étude visait à déterminer l'effet du miel sur la fréquence et la gravité de la toux chez les enfants atteints d'URTI en ambulatoire. MÉTHODES: UNE Essai contrôlé randomisé en simple aveugle impliquant des enfants présentant une toux de l'URTI et participant au GOPC de FMC Keffi. Quatre-vingt-quatre enfants présentant une toux due à l'URTI ont été recrutés, randomisés en deux groupes de 42 et administrés du miel (intervention) et de la diphenhydramine (contrôle) en trois doses consécutives au coucher. Les données sociodémographiques et cliniques, y compris la fréquence, la gravité et l'impact de la toux sur les enfants et les soignants, ont été recueillies à l'aide du questionnaire Pediatric Cough Questionnaire et de l'outil Kingston Caregiver Stress Scale. Les données ont été analysées à l'aide de la version 25 de SPSS. Un p <0,001 était considéré comme statistiquement significatif. RÉSULTATS: La majorité (56,0%) des participants étaient des hommes, avec un âge moyen de 4 ± 1,47 ans. Le score moyen de fréquence de toux pour l'intervention et le contrôle avant et après l'intervention a diminué (5,00 et 0,00 vs 5,00 et 3,00, p <0,001). Le score moyen de gravité de la toux a diminué (4,00 et 0,00 vs 4,00 et 3,00, p <0,001), le fardeau des soignants regroupés après l'intervention a été significativement réduit et le rythme de sommeil s'est amélioré chez les enfants et les soignants. CONCLUSION: Les doses nocturnes de miel administrées aux enfants avec toux par URTI réduisent considérablement les symptômes et améliorent le sommeil des enfants et des soignants par rapport au DPH. Mots clés: Fardeau du soignant; Enfant; Toux; Démulcents; Diphenhydramine; Miel ; Sommeil; Infections des voies respiratoires supérieures.


Assuntos
Antitussígenos , Demulcentes , Mel , Infecções Respiratórias , Antitussígenos/uso terapêutico , Criança , Tosse/tratamento farmacológico , Demulcentes/uso terapêutico , Difenidramina/uso terapêutico , Feminino , Humanos , Masculino , Infecções Respiratórias/complicações , Infecções Respiratórias/tratamento farmacológico , Método Simples-Cego
10.
Clin Toxicol (Phila) ; 60(10): 1122-1129, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36069771

RESUMO

BACKGROUND: Trauma centers are required to screen patients for alcohol use, and if necessary, intervene and refer to treatment (SBIRT). Similar screening for illicit drug use is recommended but not required. Urine drug screening (UDS) underestimates problematic substance use. This study aimed to estimate the types and rates of UDS false negatives (FN) compared to comprehensive testing by liquid chromatography-mass spectrometry (LC-MS) in trauma patients. METHODS: We performed a prospective cohort study of deidentified urine samples from adult trauma and burn activation patients. Both UDS and LC-MS comprehensive testing of >200 analytes were performed by a reference laboratory on all samples. Iatrogenic medications were excluded from the FN count. Crosstab analyses were conducted for UDS versus LC-MS outcomes to establish FN types and rates. We dichotomized the results by creating an "intentionality" variable (intentional injuries by self/others versus accidental injuries). A series of crosstabs with odds ratios considered intentionality by substance class and demographics. Statistically significant variables by Chi-Square were assessed by logistic regression. RESULTS: Psychoactive FN were detected in 56/100 urine samples analyzed; the most frequent included anticonvulsants (primarily gabapentin, N = 13), opioid agonists (N = 12), antihistamines (primarily diphenhydramine, N = 10), and phenethylamines (primarily bupropion, N = 5). Nonpsychoactive FN were detected in 70/100 samples; the most common were nicotine (N = 33), caffeine (N = 23), acetaminophen (N = 22), and antidepressants (N = 12). Of substance classes included in the UDS and also tested by LC-MS, FN occurred for opiates (3%), amphetamines (5%) and opioids (25%). Polypharmacy was associated with fall injuries in elderly patients. Cocaine (p = 0.015) and cannabinoids (p = 0.002) were significantly associated with intentionality. CONCLUSIONS: Our results indicate that FN for potentially important psychoactive and nonpsychoactive substances are common when toxicologic testing is limited to routine UDS in trauma patients. We recommend expanding SBIRT in this patient population to include misuse of tobacco products, prescription analgesics, and over-the-counter antihistamines.


Assuntos
Canabinoides , Cocaína , Drogas Ilícitas , Alcaloides Opiáceos , Transtornos Relacionados ao Uso de Substâncias , Adulto , Humanos , Idoso , Detecção do Abuso de Substâncias/métodos , Analgésicos Opioides/urina , Estudos Prospectivos , Gabapentina , Acetaminofen , Bupropiona , Cafeína , Nicotina , Anticonvulsivantes/uso terapêutico , Anfetaminas , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Analgésicos/uso terapêutico , Drogas Ilícitas/urina , Difenidramina
12.
Am J Emerg Med ; 60: 88-95, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35930996

RESUMO

This article highlights the most relevant emergency medicine (EM) pharmacotherapy publications indexed in 2021. A modified Delphi approach was utilized for selected journals to identify the most impactful EM pharmacotherapy studies via the GRADE system. After review of journal table of contents GRADE 1A and 1B articles were reviewed by authors. Twenty articles, 2 guidelines, 2 position papers, and 2 meta-analysis were selected for full summary. Articles included in this review highlight acute agitation management, acute appendicitis treatment, sexually transmitted infection updates, optimizing sepsis management and treatment, updates for the ideal thrombolytic agent in acute ischemic stroke and endovascular therapy candidates, indications for tranexamic acid, calicium for out of hospital cardiac arrest, optimial inotrope for cardiogenic shock, awareness during rapid sequence intubation paralysis, comparison of propofol or dexmedetomidine for sedation, treatment of cannabis hyperemsis syndrome, and prophylactic use of diphenhydramine to reduce neuroleptic side effects. Selected articles are summarized to include design, results, limitations, conclusions and impact.


Assuntos
Antipsicóticos , Dexmedetomidina , Medicina de Emergência , AVC Isquêmico , Propofol , Ácido Tranexâmico , Difenidramina , Fibrinolíticos , Humanos
13.
JAMA Psychiatry ; 79(10): 953-962, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36001306

RESUMO

Importance: Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown. Objective: To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy. Design, Setting, and Participants: In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD. Interventions: Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy. Main Outcomes and Measures: The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance. Results: A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin. Conclusions and Relevance: Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD. Trial Registration: ClinicalTrials.gov Identifier: NCT02061293.


Assuntos
Alcoolismo , Alucinógenos , Adulto , Consumo de Bebidas Alcoólicas/prevenção & controle , Alcoolismo/tratamento farmacológico , Alcoolismo/psicologia , Difenidramina/uso terapêutico , Método Duplo-Cego , Feminino , Alucinógenos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Psilocibina/uso terapêutico , Psicoterapia , Resultado do Tratamento
14.
Medicina UPB ; 41(2)julio-diciembre 2022.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1392157

RESUMO

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.


Diphenhydramine has specific anti-H1 antihistamine and antimuscarinic effects that can be fatal depending on the total dose ingested. A case of diphenhydramine poisoning successfully treated with lipid emulsions despite ingesting a lethal dose is presented. We present the case of a 19-year-old patient who was admitted for diphenhydramine intoxication at a dose of 25 mg/kg (1.5 g) after the decontamination time, with anticholinergic toxidrome, with neurotoxicity, cardiotoxicity (prolonged QRS and QT) and without response to initial approach. Lipid emulsions were started and, in turn, early discharge was achieved due to favorable clinical evolution and resolution of the prolongation of the QTc interval and the anticholinergic symptoms. Lipid emulsion is a therapeutic option to reduce morbidity and mortality and hospital stay by counteracting cardiotoxicity and neurotoxicity produced by lipophilic molecules such as diphenhydramine.


A difenidramina tem efeitos anti-histamínicos e antimuscarínicos anti-H1 específicos que podem ser fatais dependendo da dose total ingerida. Relata-se um caso de intoxicação por difenidramina tratada com sucesso com emulsões lipídicas apesar da ingestão de uma dose letal. Apresentamos o caso de uma paciente de 19 anos que foi internada por intoxicação por difenidramina na dose de 25 mg/kg (1,5 g) após o tempo de des-contaminação, com toxina anticolinérgica, neurotoxicidade, cardiotoxicidade (QS e QT prolongados) e sem resposta na abordagem inicial, iniciaram-se emulsões lipídicas e, por sua vez, obteve-se alta precoce devido à evolução clínica favorável e resolução do prolongamento do intervalo QTc e dos sintomas anticolinérgicos. A emulsão lipídica é uma opção terapêutica para reduzir a morbimortalidade e o tempo de internação por neutralizar a cardiotoxicidade e a neurotoxicidade produzidas por moléculas lipofílicas como a difenidramina.


Assuntos
Humanos , Difenidramina , Intoxicação , Antagonistas Muscarínicos , Antagonistas Colinérgicos , Emulsões , Antagonistas dos Receptores Histamínicos , Lipídeos
15.
Cardiovasc Toxicol ; 22(9): 866-877, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35930218

RESUMO

Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies medications categorized as "Known Risk of TdP" but does not stratify risk in acute supratherapeutic ingestions. We sought to determine the proportion of cases exhibiting QTc prolongation and life-threatening dysrhythmias including ventricular tachycardia (VT)/ventricular fibrillation (VF), TdP, and asystole in patients exposed to these substances. Retrospective chart review of cases reported to our Regional Poison Center from 2014 to 2019 of exposures to one or more of the "Known Risk" substances was performed. Demographics, therapies, clinical effects, and medical outcome for each case were analyzed. There were 1125 exposures, of which 760 had a documented QTc interval. QTc ≥ 500 ms was reported in 138 (18.2%) of the 760 cases. The most common "Known Risk" substances were citalopram, escitalopram and cocaine. Although not in the "Known Risk" category, mirtazapine, amitriptyline, diphenhydramine, and trazodone had a statistically significant association with QTc > 500 ms. Life-threatening dysrhythmias occurred in 13 cases, with VT/VF in 6 of the 760 (0.8%) cases, and one case of TdP. Flecainide (OR 11.1, 95% CI 2.2-55.8) and methadone (OR 7.1, 95% CI 2.1-23.4) were associated with increased risk of all life-threatening dysrhythmias. Exposures to medications on the Credible Meds list of "Known Risk of TdP" QTc prolongation is common, but life-threatening dysrhythmias are rare. Mirtazapine, amitriptyline, diphenhydramine, and trazodone were associated with prolonged QTc. Flecainide and methadone had the highest associated risk of life-threatening dysrhythmias.


Assuntos
Síndrome do QT Longo , Taquicardia Ventricular , Torsades de Pointes , Trazodona , Amitriptilina/efeitos adversos , Arritmias Cardíacas , Difenidramina/efeitos adversos , Eletrocardiografia , Flecainida/efeitos adversos , Humanos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/epidemiologia , Metadona/efeitos adversos , Mirtazapina/efeitos adversos , Centros de Controle de Intoxicações , Estudos Retrospectivos , Fatores de Risco , Taquicardia Ventricular/induzido quimicamente , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/epidemiologia , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/diagnóstico , Torsades de Pointes/epidemiologia , Trazodona/efeitos adversos , Fibrilação Ventricular
16.
PLoS One ; 17(7): e0271794, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35881585

RESUMO

Clinical testing typically relies on invasive blood draws and biopsies. Alternative methods of sample collection are continually being developed to improve patient experience; swabbing the skin is one of the least invasive sampling methods possible. To show that skin swabs in combination with untargeted mass spectrometry (metabolomics) can be used for non-invasive monitoring of an oral drug, we report the kinetics and metabolism of diphenhydramine in healthy volunteers (n = 10) over the course of 24 hours in blood and three regions of the skin. Diphenhydramine and its metabolites were observed on the skin after peak plasma levels, varying by compound and skin location, and is an illustrative example of how systemically administered molecules can be detected on the skin surface. The observation of diphenhydramine directly from the skin supports the hypothesis that both parent drug and metabolites can be qualitatively measured from a simple non-invasive swab of the skin surface. The mechanism of the drug and metabolites pathway to the skin's surface remains unknown.


Assuntos
Difenidramina , Pele , Humanos , Espectrometria de Massas , Metabolômica , Pele/metabolismo
17.
J Appl Behav Anal ; 55(4): 1258-1279, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35811329

RESUMO

Mastery criteria can be applied to individual targets or stimuli organized into sets. Wong et al. (2021) and Wong and Fienup (2022) found that participants who received special education services learned sight words more rapidly when an individual target mastery criterion was applied. The current study replicated and extended these findings across novel skills. Five participants with ASD received tact or intraverbal training in Experiment 1, and 2 participants with ASD received auditory-visual conditional discrimination training (AVCD) in Experiment 2. In both experiments, mastery criteria were applied to targets and stimulus sets to compare sessions to mastery. Results showed the target mastery criterion required fewer sessions of tact training for 3 of 5 participants and AVCD training for both participants. However, overselection of stimuli occurred for 20% of AVCD mastered targets, suggesting a false positive for acquisition of those targets. Maintenance was similar across conditions and experiments.


Assuntos
Discriminação Psicológica , Aprendizagem , Percepção Auditiva , Difenidramina , Humanos , Estimulação Luminosa , Percepção Visual
19.
Water Res ; 219: 118552, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35550969

RESUMO

Chlorine, UV254, and ozone are three typical processes commonly used for wastewater disinfection, which could change the photoreactivity of dissolved organic matter (DOM) in effluents of wastewater treatment plants (WWTPs). The photoinduced reactive species (RS) from DOM, primarily including the excited triplet state of DOM (3DOM*), singlet oxygen (1O2), and hydroxyl radical (•OH), play important roles in the attenuation of contaminants. However, the effect of disinfection processes on the photosensitized degradation of contaminants is poorly understood. This paper presents the first evidence that 3DOM*, 1O2, and •OH interaction with three typical contaminants (diphenhydramine, cimetidine, and N,N-diethyl-m-toluamide (DEET)) was largely impacted by DOM after disinfection. The results of electron spin resonance (ESR) spectrometry and laser flash photolysis (LFP) experiments demonstrated that the chlorination increased the formation rate of 3DOM* and 1O2, while UV254 irradiation and ozonation decreased the formation rate of these RS. All these three disinfection processes promoted the photoproduction of •OH and increased the photodegradation rate constants (kobs) of DEET by 26-361%. The kobs of diphenhydramine, cimetidine, and DEET correlated positively with the formation rate of 3DOM*, 1O2, and •OH, respectively. The bimolecular reaction rate constant of 3DOM* with diphenhydramine increased by ∼41% after chlorination. These findings suggest that disinfection processes altered the photogeneration of RS from DOM, which significantly impacts the fate of trace pollutants in aquatic environments.


Assuntos
Desinfecção , Poluentes Químicos da Água , 2,5-Dimetoxi-4-Metilanfetamina , Cimetidina , DEET , Difenidramina , Fotólise , Poluentes Químicos da Água/química
20.
Environ Int ; 164: 107263, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35504231

RESUMO

The main aim of the study is to evaluate the effects of the pharmaceutical diphenhydramine (DPH) on embryo-larvae Danio rerio across distinct levels of organization - individual and subcellular - and correlate those effects with the DPH mode of action (MoA) assessed by in silico analysis. An embryos heartbeat rate reduction was observed at 10 mg/L DPH, but 0.001 to 10 mg/L did not significantly affect the zebrafish survival, hatching and morphology. Larvae swimming distance decreased (hypoactivity) at 1 and 10 mg/L DPH. Moreover, the straightforward movements decrease and the increase in the zigzag movements or movements with direction changes, shown an erratic swimming behavior. Energy budgets decreased for lipid (0.01 mg/L DPH) and carbohydrate (10 mg/L DPH) contents. Cholinesterase (neural function) and glutathione S-transferase (Phase II biotransformation/antioxidant processes) increased their activities at 10 mg/L DPH, where a decrease in the total glutathione content (antioxidant system) was observed. DNA damage was found at 0.01 and 10 mg/L DPH. However, a DNA repair occurred after subsequent 72 h in clean media. The in silico study revealed a relevant conservation between human and zebrafish DPH target molecules. These data provide a valuable ecotoxicological information about the DPH effects and MoA to non-target organisms.


Assuntos
Difenidramina , Poluentes Químicos da Água , Peixe-Zebra , Animais , Antioxidantes , Difenidramina/toxicidade , Embrião não Mamífero , Humanos , Larva , Poluentes Químicos da Água/toxicidade
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