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1.
BMJ Case Rep ; 17(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453220

RESUMO

Dimenhydrinate is an over-the-counter antihistaminergic medication with anticholinergic properties used to treat nausea or motion sickness worldwide. There is a well-established correlation between the use of anticholinergic medications and dementia, however, it is unclear if a causal role exists. We report a case of minor neurocognitive disorder in a woman in her 40s with several years of high-dose daily dimenhydrinate abuse who subsequently developed significant delusional beliefs. Her clinical presentation was confounded by numerous other factors that could have impacted her cognition, such as a longstanding presumed learning disability, ankylosing spondylitis with adalimumab treatment, extensive cannabis use or potential development of a primary psychotic disorder. Her workup was within normal limits, and she has not responded to first-line antipsychotic medications to date. This case report adds to the growing evidence supporting concerns about potentially irreversible cognitive deficits in chronic misuse of anticholinergic agents, an association previously observed only in the elderly population.


Assuntos
Disfunção Cognitiva , Dimenidrinato , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Antagonistas Colinérgicos/efeitos adversos , Disfunção Cognitiva/induzido quimicamente , Dimenidrinato/efeitos adversos , Transtornos Psicóticos/tratamento farmacológico
2.
Biol Pharm Bull ; 46(10): 1394-1402, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37779040

RESUMO

Dimenhydrinate, an H1 receptor antagonist, is generally used for the prevention and treatment of nausea and vomiting. However, cardiac arrhythmias have been reported to be associated with the overdose of histamine H1 receptor antagonists, indicating the probable effect of antihistamines on ion channels. By using a two-microelectrode voltage clamp, we have herein studied the electrophysiological effects of dimenhydrinate on the human Kv1.5 channel in the Xenopus oocyte expression system. Dimenhydrinate acutely and reversibly suppressed the amplitudes of the peak and the steady-state current, within 6 min. The inhibitory effect of dimenhydrinate on the peak and the steady-state Kv1.5 currents increased progressively from -10 to +50 mV. At each test voltage, the drug suppressed both the peak and the steady-state currents to a similar extent. When the oocytes were stimulated at the rates of 5- and 30-s intervals, dimenhydrinate-induced a use-dependent blockade of the human Kv1.5 channel. Dimenhydrinate expedited the timecourse of the Kv1.5 channel activation more effectively than the timecourse of its inactivation. However, the activation and inactivation curves of the channel were not altered by the H1 receptor antagonist. In conclusion, we found that dimenhydrinate inhibits the human Kv1.5 channel by changing the channel's activation mode, thereby possibly increasing the possibility of triggering cardiac arrhythmias and affecting atrial fibrillation.


Assuntos
Dimenidrinato , Humanos , Dimenidrinato/metabolismo , Dimenidrinato/farmacologia , Fenômenos Eletrofisiológicos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Oócitos/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia
3.
Front Public Health ; 11: 1213499, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37538271

RESUMO

Objective: With the increase in aging populations worldwide, the travel well-being of the elders has gained attention. The objective of this study is to examine the nonlinear relationships between the well-being of the older people in China and factors associated with travel and health. Method: Based on the data collected in China, combined embedded feature selection and decision tree built by Gini index were utilized to screen for influential factors and to determine the importance of the features selected. Tamhane's T2 was used to study the differences in the important factors among older people with different levels of travel well-being. Results: This study found that the travel well-being of older adults depends mainly on accessibility to public places, such as schools and medical facilities, and the availability of bus services. Out of expectation, the most important influential factor of travel well-being of older people is the distance from home to high school. This is related to the traditional Chinese concept of education. In addition, it was found that the body mass index is more important than self-perceived health as an influence factor of travel well-being of the elders in China. Social skills are important factors too. Conclusion: This study investigated various health-related and travel-related factors and their impacts on the travel well-being of older adults Chinese with the overall goal to improve the quality of life of the elders in China. The findings may provide a theoretical basis for the implementation of various transportation management and urban planning and design -related policies to improve the travel well-being of older adults in China.


Assuntos
Dimenidrinato , Viagem , Humanos , Idoso , Qualidade de Vida , Doença Relacionada a Viagens , Meios de Transporte
4.
Sci Rep ; 13(1): 13549, 2023 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-37599333

RESUMO

Orphenadrine (ORP), dimenhydrinate (DMN), and cinnarizine (CNN) were investigated using green-sensitive spectrofluorometric methods. Method, I used for determination of DMN in 0.1 M hydrochloric acid (HCl) and 1.0% sodium dodecyl sulphate (SDS) at 286 nm after λex 222 nm, while for determination of ORP in 1.0% w/v SDS involves measuring the fluorescence at 285 nm after λex 220 nm. For DMN and ORP, the detection and quantitation limits were 2.99 and 4.71 and 9.08 and 14.29 ng/mL, respectively. The ranges of DMN and ORP were 0.10-1.0 and 0.04-0.5 µg/mL, respectively, in micellar aqueous solution. Method II, the derivative intensities of DMN and CNN were measured at a fixed of different wavelength between the excitation and the emission wavelengths (Δλ) = 60 nm at 282 and 322 nm, at the zero crossing of each other, respectively. The detection and quantitation limits for DMN and CNN were 1.77 and 0.88 ng/mL and 5.36 and 2.65 ng/mL, correspondingly, through the entire range of 0.1-1.0 µg/mL for DMN and CNN. The linearity was perfectly determined through the higher values of the correlation coefficient ranging from 0.9997 to 0.9999 for both direct and synchronous methods. The precision of the proposed methods was also confirmed via the lower values of the standard deviation which ranged from 0.39 to 1.11. The technique was expanded to analyze this mixture in combined tablets and laboratory-prepared mixtures. The method validation was done depending on the international conference on harmonization (ICH) recommendations. An analysis of the statistical data revealed a high agreement between the proposed data and the comparison methodology. Three different assessment methods demonstrated the greenness of the technique.


Assuntos
Cinarizina , Dimenidrinato , Orfenadrina , Espectrometria de Fluorescência , Ácido Clorídrico , Laboratórios , Espectrometria de Fluorescência/métodos
6.
Medicine (Baltimore) ; 101(38): e30661, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36197221

RESUMO

BACKGROUND: Airway neutrophilia has been associated with asthma severity and asthma exacerbations. This study attempted to identify biomarkers, pathogenesis, and therapeutic molecular targets for severe asthma in neutrophils using bioinformatics analysis. METHODS: Fifteen healthy controls and 3 patients with neutrophilic severe asthma were screened from the Gene Expression Omnibus (GEO) database. Based on the analysis of differentially expressed genes (DEGs), functional and pathway enrichment analyses, gene set enrichment analysis, protein-protein interaction network construction, and analysis were performed. Moreover, small-molecule drug candidates have also been identified. RESULTS: Three hundred and three upregulated and 59 downregulated genes were identified. Gene ontology function enrichment analyses were primarily related to inflammatory response, immune response, leukocyte migration, neutrophil chemotaxis, mitogen-activated protein kinase cascade, Jun N-terminal kinase cascade, I-kappaB kinase/nuclear factor-κB, and MyD88-dependent toll-like receptor signaling pathway. Pathway enrichment analyses and gene set enrichment analysis were mainly involved in cytokine-cytokine receptor interaction, the TNF signaling pathway, leukocyte transendothelial migration, and the NOD-like receptor signaling pathway. Furthermore, 1 important module and 10 hub genes (CXCL8, TLR2, CXCL1, ICAM1, CXCR4, FPR2, SELL, PTEN, TREM1, and LEP) were identified in the protein-protein interaction network. Moreover, indoprofen, mimosine, STOCK1N-35874, trapidil, iloprost, aminoglutethimide, ajmaline, levobunolol, ethionamide, cefaclor, dimenhydrinate, and bethanechol are potential drugs for the treatment of neutrophil-predominant severe asthma. CONCLUSION: This study identified potential biomarkers, pathogenesis, and therapeutic molecular targets for neutrophil-predominant severe asthma.


Assuntos
Asma , Dimenidrinato , Indoprofen , Levobunolol , Trapidil , Ajmalina , Aminoglutetimida , Asma/genética , Betanecol , Biomarcadores , Cefaclor , Biologia Computacional , Citocinas , Etionamida , Perfilação da Expressão Gênica , Humanos , Iloprosta , Proteínas Quinases JNK Ativadas por Mitógeno , Mimosina , Proteínas Quinases Ativadas por Mitógeno , Fator 88 de Diferenciação Mieloide , NF-kappa B , Proteínas NLR , Neutrófilos , Receptores de Citocinas , Receptor 2 Toll-Like , Receptor Gatilho 1 Expresso em Células Mieloides
7.
Cochrane Database Syst Rev ; 10: CD012715, 2022 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-36250781

RESUMO

BACKGROUND: Motion sickness is a syndrome that occurs as a result of passive body movement in response to actual motion, or the illusion of motion when exposed to virtual and moving visual environments. The most common symptoms are nausea and vomiting. Antihistamines have been used in the management of motion sickness for decades, however studies have shown conflicting results regarding their efficacy. OBJECTIVES: To assess the effectiveness of antihistamines in the prevention and treatment of motion sickness in adults and children. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 7 December 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs) in susceptible adults and children in whom motion sickness was induced under natural conditions such as air, sea and land transportation. We also included studies in which motion sickness was induced under experimental conditions (analysed separately). Antihistamines were included regardless of class, route or dosage and compared to no treatment, placebo or any other pharmacological or non-pharmacological interventions. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1) the proportion of susceptible participants who did not experience any motion sickness symptoms; 2) the proportion of susceptible participants who experienced a reduction or resolution of existing symptoms. Secondary outcomes were 1) physiological measures (heart rate, core temperature and gastric tachyarrhythmia (electrogastrography)) and 2) adverse effects (sedation, impaired cognition, blurred vision). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included nine RCTs (658 participants). Studies were conducted across seven countries, with an overall age range of 16 to 55 years. Motion sickness was induced naturally in six studies and experimentally in four studies (rotating chair). All the naturally induced studies only evaluated first-generation antihistamines (cinnarizine and dimenhydrinate). Risk of bias across the studies varied, with mostly low risk for random sequence generation and allocation concealment, and mostly high risk for selective reporting. Only the experimentally induced studies measured physiological parameters and only the naturally induced studies evaluated adverse effects. There were no studies that clearly assessed the paediatric population. Antihistamines versus placebo or no treatment Antihistamines are probably more effective than placebo at preventing motion sickness symptoms under natural conditions (symptoms prevented: 25% placebo; 40% antihistamines) (risk ratio (RR) 1.81, 95% confidence interval (CI) 1.23 to 2.66; 3 studies; 240 participants) (moderate-certainty). The evidence is very uncertain about the effect of antihistamines on preventing motion sickness under experimental conditions (standardised mean difference (SMD) 0.32, 95% CI -0.18 to 0.83; 2 studies; 62 participants) (very low-certainty). No studies reported results on the resolution of existing motion sickness symptoms. Antihistamines may result in little or no difference in gastric tachyarrhythmia under experimental conditions (mean difference (MD) -2.2, 95% CI -11.71 to 7.31; 1 study; 42 participants) (low-certainty). No studies reported results for any other physiological measures. When compared to placebo, antihistamines may be more likely to cause sedation (sedation: 44% placebo; 66% antihistamines) (RR 1.51, 95% CI 1.12 to 2.02; 2 studies; 190 participants) (low-certainty); they may result in little or no difference in blurred vision (blurred vision: 12.5% placebo; 14% antihistamines) (RR 1.14, 95% CI 0.53 to 2.48; 2 studies; 190 participants) (low-certainty); and they may result in little or no difference in terms of impaired cognition (impaired cognition: 33% placebo; 29% antihistamines) (RR 0.89, 95% CI 0.58 to 1.38; 2 studies; 190 participants) (low-certainty). Antihistamines versus scopolamine The evidence is very uncertain about the effect of antihistamines on preventing motion sickness under natural conditions when compared to scopolamine (symptoms prevented: 81% scopolamine; 71% antihistamines) (RR 0.89, 95% CI 0.68 to 1.16; 2 studies; 71 participants) (very low-certainty). No studies were performed under experimental conditions. No studies reported results on the resolution of existing motion sickness symptoms. The evidence is very uncertain about the effect of antihistamines on heart rate under natural conditions (narrative report, 1 study; 20 participants; "No difference in pulse frequency"; very low-certainty). No studies reported results for any other physiological measures. When compared to scopolamine, the evidence is very uncertain about the effect of antihistamines on sedation (sedation: 21% scopolamine; 30% antihistamines) (RR 0.82, 95% CI 0.07 to 9.25; 2 studies; 90 participants) (very low-certainty) and on blurred vision (narrative report: not a significant difference; 1 study; 51 participants; very low-certainty). No studies evaluated impaired cognition. Antihistamines versus antiemetics Antihistamines may result in little or no difference in the prevention of motion sickness under experimental conditions (MD -0.20, 95% CI -10.91 to 10.51; 1 study; 42 participants) (low-certainty). The evidence is of low certainty due to imprecision as the sample size is small and the confidence interval crosses the line of no effect. No studies assessed the effects of antihistamines versus antiemetics under natural conditions. No studies reported results on the resolution of existing motion sickness symptoms. Antihistamines may result in little or no difference in gastric tachyarrhythmia (MD 4.56, 95% CI -3.49 to 12.61; 1 study; 42 participants) (low-certainty). No studies reported results for any other physiological measures. No studies evaluated sedation, impaired cognition or blurred vision. One study reported physiological data for this outcome, evaluating gastric tachyarrhythmia specifically. Antihistamines may result in little or no difference in gastric tachyarrhythmia (MD 4.56, 95% CI -3.49 to 12.61; 1 study; 42 participants; low-certainty evidence). This evidence is of low certainty due to imprecision as the sample size is small and the confidence interval crosses the line of no effect. Antihistamines versus acupuncture The evidence is very uncertain about the effects of antihistamines on the prevention of motion sickness under experimental conditions when compared to acupuncture (RR 1.32, 95% CI 1.12 to 1.57; 1 study; 100 participants) (very low-certainty). This study did not assess the prevention of motion sickness under natural conditions, nor the resolution of existing motion sickness symptoms. There was no study performed under natural conditions. Physiological measures and adverse effects were not reported. AUTHORS' CONCLUSIONS: There is probably a reduction in the risk of developing motion sickness symptoms under naturally occurring conditions of motion when using first-generation antihistamines, in motion sickness-susceptible adults, compared to placebo. Antihistamines may be more likely to cause sedation when compared to placebo. No studies evaluated the treatment of existing motion sickness, and there are few data on the effect of antihistamines in children. The evidence for all other outcomes and comparisons (versus scopolamine, antiemetics and acupuncture) was of low or very low certainty and we are therefore uncertain about these effects of antihistamines.


Assuntos
Antieméticos , Cinarizina , Dimenidrinato , Enjoo devido ao Movimento , Adolescente , Adulto , Criança , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Pessoa de Meia-Idade , Enjoo devido ao Movimento/tratamento farmacológico , Derivados da Escopolamina , Adulto Jovem
8.
Clin Drug Investig ; 42(9): 705-720, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35864302

RESUMO

BACKGROUND AND OBJECTIVE: The source data of four individual randomised, double-blind, reference- and/or placebo-controlled clinical trials with virtually identical study design were pooled for the present meta-analysis. The main objective was to further evaluate the efficacy and safety of the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg in comparison to various other antivertigo treatments in patients suffering from central and/or peripheral vestibular vertigo. METHODS: Adult male and female outpatients were subjected to a 4-week treatment with the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg, cinnarizine (20 mg, 50 mg), dimenhydrinate (40 mg, 100 mg), betahistine dimesylate (12 mg), betahistine dihydrochloride (16 mg) and placebo, respectively. The primary efficacy endpoint was the reduction of a validated mean vertigo score (MVS), a composite score of 12 individual vertigo symptoms, the intensities of which were each evaluated by the patients on a 5-point visual analogue scale. For analysis of primary and further secondary efficacy endpoints, baseline-adjusted analysis of covariance (ANCOVA) was used to calculate adjusted least squares means (LSM) with associated two-sided 95% confidence intervals (CIs) for the difference in MVS reductions between treatment groups. Moreover, various sensitivity analyses, responder and subgroup analyses as well as descriptive analyses with respect to safety/tolerability of the treatments were conducted. RESULTS: Of 795 randomised patients, 779 belonged to the intent-to treat (ITT) and 723 to the per-protocol (PP) population. The main efficacy analysis was based on the ITT population (mean age 52.1 years, 61% female). The mean decrease of the MVS from baseline to Week 4 in the cinnarizine/dimenhydrinate group (-1.10) proved to be significantly larger than in any of the comparator groups. LSM differences for comparators versus the fixed combination ranged between 0.16 (95% confidence interval (CI) 0.03; 0.30, p = 0.017) for cinnarizine 20 mg and 0.60 (95% CI 0.42; 0.78; p < 0.001) for betahistine dimesylate 12 mg in favour of the fixed combination. Furthermore, after 4 weeks of treatment, 74 patients (24.7%) in the cinnarizine/dimenhydrinate group were completely symptom free (MVS = 0), a significantly greater proportion than in any of the comparator groups. Sensitivity analyses showed that baseline characteristics such as age, sex, duration of vertigo and antivertigo pretreatment had only a very minor and clinically non-relevant impact on the efficacy results regarding the primary efficacy outcome. Subgroup analyses with respect to age groups (< 65 years/≥ 65 years) and sex showed no significant differences in efficacy within any of the treatment groups. All treatments were well tolerated. A total of 55 patients (6.9%) reported 75 non-serious adverse events (AEs), and 19 patients (2.4%) discontinued the study prematurely because of AEs. Nearly 95% of the patients (cinnarizine/dimenhydrinate group: 97.9%) rated the tolerability of the study medications as either "good" or "very good". CONCLUSION: The findings of the present meta-analysis indicate that the fixed combination of cinnarizine and dimenhydrinate is a safe and potentially superior treatment option for patients suffering from central and/or peripheral vestibular vertigo, as compared to current standard treatments such as cinnarizine, dimenhydrinate or betahistine given alone in monotherapy.


Assuntos
Cinarizina , Dimenidrinato , Adulto , Idoso , beta-Histina/efeitos adversos , Cinarizina/efeitos adversos , Dimenidrinato/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Vertigem/tratamento farmacológico
9.
Braz J Biol ; 84: e260566, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35613215

RESUMO

Chrozophora tinctoria (L.) A.Juss. is herbaceous, monecious annual plant used traditionally to cure gastrointestinal disorders. The present study was carried out to find the bioactive compounds by Gas Chromatography-Mass Spectrometry, the acetylcholinesterase inhibitory potential acute toxicity, and emetic activity present in the ethyl acetate fraction of Chrozophora tinctoria (EAFCT) and dichloromethane fraction of Chrozophora tinctoria (DCMFCT). The compounds detected in both fractions were mostly fatty acids, with about seven compounds in EAFCT and 10 in DCMFCT. These included pharmacologically active compounds such as imipramine, used to treat depression, or hexadecanoic acid methyl ester, an antioxidant, nematicide, pesticide, hypocholesterolemic, 9,12,15-Octadecatrienoic acid, ethyl ester, (Z,Z,Z)- is used as a cancer preventive, antiarthritic, antihistaminic, hepatoprotective, insectifuge, nematicide, Pentadecanoic acid, 14-methyl-, methyl ester have antifungal, antimicrobial and antioxidant activities, 10-Octadecanoic acid, methyl ester have the property to decrease blood cholesterol, Antioxidant and antimicrobial, 1-Eicosanol is used as an antibacterial, 1-Hexadecene has antibacterial, antioxidant, and antifungal activities. Both DCMFCT and EAFCT fractions inhibited acetylcholinesterase (AChE) activity with IC50 values of 10 µg and 130 µg, respectively. Both the fractions were found to be toxic in a dose-dependent manner, inducing emesis at 0.5g onward and lethargy and mortality from 3-5 g upwards. Both the fractions combined with distilled water showed highly emetic activity. The significant increase in the number of vomits was shown by EAFCT plus distilled water which are 7.50±1.29, 7.25±3.10, and 11.75±2.22 number of vomits at 1g, 2g, and 3g/kg concentration respectively, while DCMFCT plus distilled water showed 5.25±2.22, 7.50±2.52 and 10.25±2.22 number of vomits at 1g, 2, and 3g/kg correspondingly. The antiemetic standard drug metoclopramide has a higher impact against the emesis induced by both the fractions than dimenhydrinate. Metoclopramide decreases the number of vomits caused by EAFCT to 1.00±0.00, 2.00±0.00, 4.00±1.00 at 1g, 2, and 3g/kg sequentially, while dimenhydrinate decreases the number of vomits to 1.33±0.58, 2.33±1.15, 4.33±0.58 at 1g, 2, and 3g respectively. In the same way, Metochloprimide decreases the number of emesis caused by DcmCt from 5.25±2.22, 7.50±2.52, 10.25±2.22 to 1.33±0.58, 2.33±1.1, 4.33±0.58 at 1g, 2, and 3g/kg concentrations. The present study is the first documented report that scientifically validates the folkloric use of Chrozophora tinctoria as an emetic agent.


Assuntos
Dimenidrinato , Euphorbiaceae , Acetilcolinesterase , Animais , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Dimenidrinato/análise , Eméticos/análise , Ésteres/análise , Cromatografia Gasosa-Espectrometria de Massas , Metoclopramida/análise , Modelos Animais , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Vômito , Água
10.
Wilderness Environ Med ; 33(2): 148-153, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35361528

RESUMO

INTRODUCTION: Acute altitude exposure is a common event in Latin America that can result in mild to severe altitude illness. Medical students from some Latin American countries receive little information on this topic. Our aim was to determine the knowledge and incidence of acute mountain sickness (AMS), as well as the methods used to prevent AMS among medical students attending the Pan-American Student Meeting in Cusco, Peru, a city at high altitude (3400 m). METHODS: We conducted a cross-sectional study on medical students attending a conference. Participants completed a questionnaire on the day of registration that collected demographic data and investigated students' knowledge of AMS, its prophylaxis, and their personal experience of symptoms. RESULTS: A total of 840 students attended the meeting. Two hundred eighty-eight returned surveys, 51 from high altitude locations. Respondent age was 23±3 y (mean±SD), and 72% were female. Thirty-two percent had basic knowledge about symptoms of AMS. Headache was recognized as a symptom by 79%. Knowledge of AMS prophylaxis was reported by 70%. Coca leaf products and dimenhydrinate were mentioned by 30 and 16%, respectively, whereas acetazolamide was recognized by only 10% of participants. AMS incidence was 42%. Prophylactic measures were adopted by 47% of the participants in our study. Thirty-six percent used dimenhydrinate and 27% used coca tea. Less than 1% used acetazolamide as recommended. CONCLUSIONS: We found poor knowledge of AMS and effective prophylaxis among medical students from several South American countries traveling to 3400 m.


Assuntos
Doença da Altitude , Dimenidrinato , Estudantes de Medicina , Acetazolamida/uso terapêutico , Doença Aguda , Doença da Altitude/diagnóstico , Doença da Altitude/epidemiologia , Doença da Altitude/prevenção & controle , Estudos Transversais , Dimenidrinato/uso terapêutico , Feminino , Humanos , América Latina/epidemiologia , Masculino
11.
Pak J Pharm Sci ; 34(1(Supplementary)): 245-255, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34275848

RESUMO

Development of dimenhydrinate (DMN) emulgel formulation has been described in this work with enhanced permeation for transdermal delivery of DMN for effective management of motion sickness. Various DMN emulgel formulations were prepared using central composite design in response surface methodology. Propylene glycol and olive oil were used in varying ratios as permeation enhancers along-with carbopol-934 as gelling agent. Prepared formulations were evaluated by physico-chemical properties, stability and Fourier transform infrared spectroscopy (FTIR) studies. In-vitro drug release was studied using cellophane membrane. Formulation F2 showed maximum drug permeation following diffusion-based release mechanism and was used in further studies. Rat skin was used in Franz cell for ex-vivo studies to determine various permeation kinetic parameters. FTIR studies provided no evidence of chemical interaction between DMN and polymers used, whereas molecular docking revealed formation of a stable complex in the presence of aqueous environment with stable intermolecular binding and the complex was well hydrated. No evidence of skin irritation was observed in human volunteers following application of the optimized formulation. Histopathology data of the rat skin showed a decreased proliferation of the lymphocytes whereas monocytes were induced. In conclusion, combination of propylene glycol and olive oil was successfully employed for delivery of DMN through transdermal route with good permeability and prolonged release time that can be highly beneficial in treating motion sickness in unusual circumstances.


Assuntos
Antieméticos/administração & dosagem , Dimenidrinato/administração & dosagem , Emulsões , Géis , Azeite de Oliva , Propilenoglicol , Pele/metabolismo , Administração Cutânea , Animais , Antieméticos/farmacocinética , Dimenidrinato/farmacocinética , Sistemas de Liberação de Medicamentos , Simulação de Acoplamento Molecular , Enjoo devido ao Movimento/tratamento farmacológico , Ratos , Absorção Cutânea , Espectroscopia de Infravermelho com Transformada de Fourier
12.
Artigo em Inglês | MEDLINE | ID: mdl-33946152

RESUMO

Vertigo is not itself a disease, but rather a symptom of various syndromes and disorders that jeopardize balance function, which is essential for daily activities. It is an abnormal sensation of motion that usually occurs in the absence of motion, or when a motion is sensed inaccurately. Due to the complexity of the etiopathogenesis of vertigo, many pharmacological treatments have been tested for efficacy on vertigo. Among these drugs, cinnarizine, usually given together with dimenhydrinate, appears to be the first-line pharmacotherapy for the management of vertigo and inner ear disorders. Based on these considerations, the present non-interventional study aimed to investigate the clinical efficacy and tolerability of a fixed combination of cinnarizine (20 mg) and dimenhydrinate (40 mg) in patients suffering from vertigo-related symptoms. To this end, we enrolled 120 adults-70 males, and 50 females-with an average age of 64 years. Before beginning pharmacological treatment, all patients were screened for the intensity of vertigo, dizziness, and concomitant symptoms through the Visual Scale of Dizziness Disorders and Dizziness Handicap Inventory scales. At the end of the anamnestic evaluation, patients received the fixed-dose combination of cinnarizine (20 mg) plus dimenhydrinate (40 mg) 3 times daily, for 60 days. The results of this study provide further insight regarding the efficacy of the fixed combination when used to reduce symptoms of vestibular vertigo of central and/or peripheral origin, after both the 15- and 60-day therapies. Independent of the type of vertigo, the fixed combination was able to reduce dizziness- and vertigo-associated symptoms in more than 75% of all patients treated, starting from 15 days of therapy, and improving 60 days after starting the therapy. Interestingly, we also found differences between male and female patients in the framework of the pharmacological effects of therapy. This study provides further details concerning the therapeutic efficacy of the fixed combination of cinnarizine and dimenhydrinate, and also focuses attention on the possibility that these drugs could act in a gender-specific manner, paving the way for further research.


Assuntos
Cinarizina , Dimenidrinato , Adulto , Cinarizina/uso terapêutico , Dimenidrinato/uso terapêutico , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Vertigem/tratamento farmacológico , Vertigem/etiologia
13.
Am J Emerg Med ; 40: 77-82, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33360021

RESUMO

BACKGROUND: This study aimed to compare the therapeutic efficacy of dimenhydrinate and metoclopramide in patients with nausea and vertigo. METHODS: A prospective, double-blind, randomized clinical trial was performed on patients who presented to the emergency department (ED) with nausea and vertigo in the six month period between Nov 1st 2012 and May 1st 2013. Adult patients who were 18 to 65 years old presenting to the ED with nausea and vertigo or motion sickness were included in the study. A total of 200 patients were divided into 2 groups who were admitted to ED with complaints of vertigo accompanied by nausea. In the first group, 50 mg dimenhydrinate and 10 mg metoclopramide infusions were given intravenously for 15 min. The efficacy of treatment was measured by using a 10 mm Visual Analog Scale (VAS) performed at 0, 15 and the 30th minute. The primary outcome variable was a reduction in vertigo intensity documented on the VAS at the 30th minute after medication administration. RESULTS: A total of 200 patients were included in the randomization (n=100 in both groups). The baseline vertigo VAS scores were 7.57±1.42 in the dimenhydrinate (DMT) group and 7.27±1.40 in the metoclopramide (MTP) group (p=0.09). In the 30th minute of treatment, the average vertigo VAS score was 2.46 ± 2.39 in the DMT group and 2.31±1.96 in the MTP group; no significant differences were detected between groups. The baseline nausea VAS scores were 7.62±1.48 in the DMT group and 7.45±1.27 in the MTP group (p=0.36). In the 30th minute of treatment the average vertigo VAS score decreased to 2.27±2.24 in the DMT group and 2.70±2.48 in the MTP group, no significant differences were detected between groups. No significant differences were detected between nausea VAS changes and vertigo VAS changes at 30th minutes of the treatment (p=0.06, p=0.85 respectively). Rescue medication need was similar in both treatment groups (p=0.94). No significant differences were detected about the side effects which are sedation (p=0.56) and hypotension (p=0.57). CONCLUSIONS: In conclusion, this prospective, double-blind, randomized study showed that both DMT and MTP have similar efficacy in reducing nausea and vertigo symptoms in the ED.


Assuntos
Antieméticos/uso terapêutico , Dimenidrinato/uso terapêutico , Serviço Hospitalar de Emergência , Metoclopramida/uso terapêutico , Náusea/tratamento farmacológico , Náusea/etiologia , Vertigem/tratamento farmacológico , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vertigem/complicações
14.
J Psychiatr Res ; 136: 581-588, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33153760

RESUMO

BACKGROUND: Dimenhydrinate (DMH) is an antihistamine used to treat nausea and vomiting. Although widely available in pharmacies as an over the counter medication, there have been reports of potential DMH tolerance and dependence and a possible euphoric potential accompanying heavy use (>100 mg/day). Despite the potential for misuse, there is a gap in the literature concerning patterns, characteristics, and potential mechanisms of DMH misuse. AIMS: This review aimed to synthesize evidence on the pharmacology, clinical effects, and management of DMH misuse and dependence to inform clinical decision making and relevant drug policy. METHODS: We conducted a systematic review in accordance with the PRISMA guidelines and using Cochrane collaboration methods. We searched seven databases from their inception through July 2019. To be included in the review, studies needed to measure or focus on one or more dimensions of morbidity or mortality related to the misuse of DMH. Quantitative, qualitative and mixed-method studies were included in order to capture the breadth of possible studies. Studies were excluded if they did not fit into the conceptual framework of the study of if they focused primarily on the misuse of other substances. A narrative synthesis of study findings was pursued given the limited capacity for a quantitative meta-analysis. FINDINGS: We identified 24 studies, which described a range of neuropsychiatric sequelae related to DMH consumption, including seizures, psychosis, depression, intoxication (resembling anticholinergic syndrome) and withdrawal. The sedative and euphoric properties, readily available nature, and low cost of DMH appear to facilitate DMH dependence, which were more commonly reported among individuals who had concurrent psychiatric disorders, displaying symptoms such as low motivation, poor concentration, and delirium. The overall quality of studies identified by this review was low-largely because the majority of studies were case reports or review articles, with few intervention or cohort studies. CONCLUSIONS: There is some evidence to suggest the existence of DMH-related syndromes involving intoxication, withdrawal, and dependence, more commonly among long-term, heavy DMH consumers. However, higher quality studies are needed to confirm preliminary findings that there may be a biological basis for such syndromes.


Assuntos
Dimenidrinato , Transtornos Psicóticos , Humanos
15.
Pediatrics ; 145(4)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32132152

RESUMO

CONTEXT: Several antiemetics have been used in children with acute gastroenteritis. However, there is still controversy over their use. OBJECTIVE: To determine the effectiveness and safety of antiemetics for controlling vomiting in children with acute gastroenteritis. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Latin America and the Caribbean Literature on Health Sciences, and gray literature, until December 2018. STUDY SELECTION: We selected randomized clinical trials comparing metoclopramide, ondansetron, domperidone, dexamethasone, dimenhydrinate, and granisetron. DATA EXTRACTION: Two reviewers independently screened abstracts and full texts, extracted the data, and assessed the risk of bias. We performed pairwise and network meta-analysis using the random-effects model. RESULTS: Twenty-four studies were included (3482 children). Ondansetron revealed the largest effect in comparison to placebo for cessation of vomiting (odds ratio = 0.28 [95% credible interval = 0.16 to 0.46]; quality of evidence: high) and for hospitalization (odds ratio = 2.93 [95% credible interval = 1.69 to 6.18]; quality of evidence: moderate). Ondansetron was the only intervention that reduced the need for intravenous rehydration and the number of vomiting episodes. When considering side effects, dimenhydrinate was the only intervention that was worse than placebo. LIMITATIONS: Most treatment comparisons had low- or very low-quality evidence, because of risk of biases and imprecise estimates. CONCLUSIONS: Ondansetron is the only intervention that revealed an effect on the cessation of vomiting, on preventing hospitalizations, and in reducing the need for intravenous rehydration. Ondansetron was also considered a safe intervention.


Assuntos
Antieméticos/uso terapêutico , Gastroenterite/complicações , Vômito/tratamento farmacológico , Doença Aguda , Antieméticos/efeitos adversos , Criança , Pré-Escolar , Dexametasona/uso terapêutico , Diarreia/induzido quimicamente , Dimenidrinato/uso terapêutico , Domperidona/uso terapêutico , Hidratação/estatística & dados numéricos , Granisetron/uso terapêutico , Hospitalização , Humanos , Lactente , Metoclopramida/uso terapêutico , Metanálise em Rede , Ondansetron/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Vômito/complicações
19.
Ann Otol Rhinol Laryngol ; 129(5): 434-440, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31810393

RESUMO

OBJECTIVES: The aim of this study was to compare the effects of betahistine with dimenhydrinate on the resolution of residual dizziness (RD) of patients with benign paroxysmal positional vertigo (BPPV) after successful Epley maneuver. METHODS: In this double-blind, randomized clinical trial, patients with posterior semicircular canal type of BPPV were included. After execution of the Epley maneuver, patients were assigned randomly to one group for 1 week: betahistine, dimenhydrinate or placebo. The primary outcomes were scores of the Dizziness Handicap Inventory (DHI) and the modified Berg balance scale (mBBS). All patients were asked to describe the characteristics of their subjective residual symptoms. Binary logistic regression analysis was performed to examine the predictors of improved RD. All analyses were conducted using SPSS 19.0. RESULTS: In total, 117 patients (age range: 20-65 years) participated in this study. After the Epley maneuver, 88 participants had RD. After the intervention, 38 patients exhibited an improved RD. Less than 50% of participants in the three groups showed mild to moderate dizziness handicap. However, there was no significant difference between mBBS scores of groups before or after the intervention. Logistic regression was shown that patients with receiving betahistine were 3.18 times more likely to have no RD than the placebo group. Increasing age was associated with a decreased likelihood of improving RD (P = .05). CONCLUSION: The analysis of data showed that the use of betahistine had more effect on improving RD symptoms. We recommended future studies using objective indicators of residual dizziness.


Assuntos
Vertigem Posicional Paroxística Benigna/complicações , beta-Histina/uso terapêutico , Dimenidrinato/uso terapêutico , Tontura/tratamento farmacológico , Adolescente , Adulto , Idoso , Vertigem Posicional Paroxística Benigna/tratamento farmacológico , Vertigem Posicional Paroxística Benigna/fisiopatologia , Tontura/etiologia , Método Duplo-Cego , Feminino , Seguimentos , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Vasodilatadores/uso terapêutico , Adulto Jovem
20.
Clin Drug Investig ; 39(11): 1045-1056, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31571128

RESUMO

BACKGROUND AND OBJECTIVE: Vertigo derived from peripheral vestibular disorders is quite frequently encountered in daily clinical practice and can be a severely disabling symptom associated with substantial impairment of health-related quality of life for the affected patients. Betahistine, a structural analogue of histamine and presumably the most widely prescribed anti-vertigo drug worldwide, has previously been shown to be an effective and safe treatment for these patients. The objective of the present study was to evaluate whether the fixed combination of cinnarizine and dimenhydrinate (Arlevert®) is non-inferior and thus a potentially useful alternative to betahistine dihydrochloride in the treatment of patients suffering from peripheral vestibular vertigo. METHODS: In this prospective, multicenter, double-blind, randomized, non-inferiority clinical trial, outpatients from 8 ENT clinics in Austria, Bulgaria, the Czech Republic and Russia were randomly assigned to receive three times daily one tablet of either the fixed combination cinnarizine 20 mg/dimenhydrinate 40 mg or betahistine dihydrochloride 16 mg for 4 weeks. Primary endpoint was the reduction of the mean vertigo score (MVS), a validated 12-item composite score defined as the mean of 6 vertigo symptoms (dystasia and walking unsteadiness, staggering, rotary sensation, tendency to fall, lift sensation, blackout) and 6 trigger factors for vertigo (change of position, bowing, getting up, driving by car/train, head movements, eye movement), after 4 weeks of therapy, as judged by the patient on a 5-point visual analogue scale (VAS). The non-inferiority margin was set to 0.3. Secondary outcomes included the patient's and investigator's judgment of global efficacy, the patient's rating of impairment of daily activities, and safety/tolerability of the treatments. RESULTS: Three hundred and six patients (mean age 53.5 years, approximately 60% female) were enrolled and randomized to the fixed combination cinnarizine/dimenhydrinate (n = 152) or betahistine (n = 154) groups; 297 patients completed the study and 294 (146 and 148, respectively) were valid for the per-protocol analysis, which was used for the non-inferiority analysis. Treatment with cinnarizine/dimenhydrinate led to a stronger reduction of the MVS [least squares mean (LSM)] after 4-week therapy (primary endpoint) in comparison to betahistine (0.395 vs 0.488; difference: - 0.093, 95% CI - 0.180; - 0.007, p = 0.035); since the upper limit of the two-sided 95% confidence interval was not only below the non-inferiority margin of 0.3, but also entirely below 0, superiority of the fixed combination could be demonstrated. The combination preparation was also more effective after 1 week of therapy and received more favorable patient's ratings on overall efficacy and impairment of daily activities. Both treatments were very well tolerated. Only 12 patients (3.92%) reported 13 non-serious adverse events; 2 cinnarizine/dimenhydrinate-treated patients discontinued the study prematurely due to adverse events as compared to 5 betahistine-treated patients. CONCLUSION: The fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg was found to be not only non-inferior, but superior to betahistine 16 mg in the improvement of peripheral vestibular vertigo. Furthermore, taking into account a good and slightly favorable safety profile, the present study provides evidence that the fixed-combination preparation is a potent and even superior alternative to betahistine in the treatment of vertigo related to peripheral vestibular disorders. STUDY REGISTRATION: EudraCT No. 2011-004025-27.


Assuntos
beta-Histina/uso terapêutico , Cinarizina/uso terapêutico , Dimenidrinato/uso terapêutico , Vertigem/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , beta-Histina/efeitos adversos , Cinarizina/efeitos adversos , Dimenidrinato/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
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