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Colon rectal cancer (CRC) is the second commonest malignancy in developed countries and a significant cause of mortality. Tenofovir reportedly reduces the risk of hepatocellular carcinoma and interferes with cell cycle and cell proliferation. The current study investigated the potential antitumor effect of tenofovir against experimentally induced CRC. CRC was induced by 1,2-dimethylhydrazine (DMH, 20 mg/kg, once a week) and high-fat diet (HFD) in Wistar rats. Rats received tenofovir at a dose of 25 or 50 mg/kg (i.p.) for 24 weeks. Tenofovir-25 failed to significantly decrease the total number of dysplasia, adenoma and adenocarcinoma and to improve histopathological changes; however, tenofovir-50 resulted in no tumors seen in the colon lumen and a significant decrease in the total number of dysplasia and no adenoma or adenocarcinoma observed compared to DMH/HFD group. Tenofovir-25 failed to attenuate DMH/HFD-induced cell proliferation, whereas tenofovir-50 significantly decreased cell proliferation revealed by the decreased PCNA expression. Tenofovir-25 also failed to attenuate DMH/HFD-induced oxidative stress, whereas tenofovir-50 significantly attenuated oxidative stress as indicated by the decreased MDA concentration and SOD activity along with the increased GSH concentrations. Moreover, tenofovir-50 decreased Bcl-2 and cyclin D1 expressions in colon tissues compared with DMH/HFD group. Tenofovir-50 also significantly decreased INF-ɤ concentration in colon tissues. These findings suggest that the high dose of tenofovir (50 mg/kg) has antitumor potential against DMH/HFD-induced CRC, which might be mediated through the inhibition of cell proliferation, oxidative stress, and inflammation.

The paper describes the current state of development of seasickness as one of movement disease variants. The given type of pathology occurs when combining different types of ship’s motion (rolling and pitching). Circular, vertical and slow movements induce more pronounced and frequent signs of seasickness than linear, horizontal and quick ones. In the view of majority of researchers, the most likely is an intersensory conflict theory i.e. violation of coherent functioning of afferent body systems performing spatial orientation, statokinetic equilibrium and keeping balance. The leading role is played by the functional dysfunction of the vestibular analyzer. The classification of means of preventing and stopping of motion sickness is given, the mechanisms of their action, specific activity and side effects are described. It has been shown that currently the most effective drugs are M-cholinergic antagonists (scopolamine hydrobromide) and H1-histamine antagonists of the 1st generation (dimenhydrinate, diphenhydramine, cyclizine, meclizine, promethazine, etc.). Of the antipsychotics and blockers of D2receptors, prochlorperazine and metoclopramide are recommended. It is also worth to use prokinetics (domperidone, cisapride, renzapride, etc.), tranquilizers (barbiturates, benzodiazepines), sleeping pills and local anesthetics. Particular attention is paid to combination drugs, consisting of antiemetic and psychostimulating drugs, designed to maintain working capacity under the influence of seasickness factors on the body. Non-pharmacological means of preventing seasickness and alleviating its symptoms are described. The main directions of improving the system of measures aimed at maintaining efficiency in the presence of symptoms of seasickness are determined.

KEY POINTSAt 4:00 am, a 71-year-old man turned over in bed onto his left side and experienced a sudden onset of dizziness, described as if the bed was moving. Although lasting only 10–15 seconds, he became sweaty afterwards without nausea or vomiting. He came to the emergency department an hour

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.

Background: Over the past 20 years or so, the drug misuse scenario has seen the emergence of both prescription-only and over-the-counter (OTC) medications being reported as ingested for recreational purposes. OTC drugs such as antihistamines, cough/cold medications, and decongestants are reportedly the most popular in being diverted and misused.Objective: While the current related knowledge is limited, the aim here was to examine the published clinical data on OTC misuse, focusing on antihistamines (e.g., diphenhydramine, promethazine, chlorpheniramine, and dimenhydrinate), dextromethorphan (DXM)- and codeine-based cough medicines, and the nasal decongestant pseudoephedrine.Methods: A systematic literature review was carried out with the help of Scopus, Web of Science databases, and the related gray literature. For data gathering purposes, both the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and PROSPERO guidelines were followed (PROSPERO identification code CRD42020209261).Results: After completion of the selection, eligibility, and screening phases, some 92 articles were here taken into consideration; case reports, surveys, and retrospective case series analyses were included. Findings were organized according to the specific OTC recorded. Most articles focused here on DXM (n = 54) and diphenhydramine (n = 12). When specified, dosages, route(s) of administration, toxicity symptoms (including both physical and psychiatric ones), and outcomes were here reported.Conclusion: Results from the systematic review showed that the OTC misusing issues are both widespread worldwide and popular; vulnerable categories include adolescents and young adults, although real prevalence figures remain unknown, due to a lack of appropriate monitoring systems. Considering the potential, and at times serious, adverse effects associated with OTC misusing issues, healthcare professionals should be vigilant, and ad hoc preventative actions should be designed and implemented.

Introduction: The Mean Vertigo Score (MVS) is a composite score for defining the burden of disease of patients suffering from vestibular disorders. It has been used in clinical research for about 30 years. This study investigates discriminant validity of the MVS and describes structural relationships of the 12 single criteria used for construction of the MVS.Materials and Methods: The statistical analyses are based on the raw data of an earlier conducted randomized, doubleblind, placebo-controlled clinical trial, which compared the following four randomized treatment groups: a fixed combination of cinnarizine and dimenhydrinate (Arlevert), two groups with only one of the two study drugs, and a group with placebo. The method used for the statistical calculations is the Wei-Lachin procedure, a multivariate generalization of the Mann-Whitney test, which takes into account correlations among the 12 single symptoms of the composite score.Results: All 12 single symptoms of the composite endpoint proved to be useful for detecting differences (Mann-Whitney effect size measures: 0.58–0.73) and thus for discriminating between treatment groups. Their Pearson product-moment correlations are all positive (range 0.07–0.71) and point to the same direction, which indicates one-dimensionality and good internal consistency of the composite index MVS. Furthermore, our statistical calculations revealed that successively increasing the number of single items of the MVS to up to twelve enhances its reliability (R12 = 0.923), which leads to a substantially higher test power and reduction of the number of patients needed (sample size) in a clinical trial.Conclusion: The use of the multivariate Wei-Lachin procedure provides further evidence of the validity of the 12-item composite score MVS, based on the efficacy data of its 12 single vertigo symptoms. The present findings demonstrate that the MVS is a powerful tool, which can be used to adequately describe the patients' self-perceived vertigo complaints, both qualitatively and quantitatively. It may therefore be regarded as a clinically meaningful alternative to other questionnaires that are presently used in vestibular research.

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.

Obesity is associated with chronic inflammation, intestinal dysbiosis, and colorectal cancer risk. The anti-cancer effects of kefir are highlighted. Here, lactating Wistar rats were divided into: Normal litter (NL); Kefir normal litter (KNL); Small litter (SL); Kefir small litter (KSL). The NL and SL groups received 1 mL of water/day; KNL and KSL received kefir milk daily (108 CFU/mL) during lactation. After weaning, the pups continued to receive the same treatments until 60 days. At 67 days old, colorectal carcinogenesis was induced through intraperitoneal injection of 1,2-dimethylhydrazine. At 240 days, visceral adipose tissue was higher in SL compared to NL, KNL, and KSL. Kefir intake was found to suppress the number of tumors in both KNL and KSL groups (-100% and −71.43%; p

Background: Medication use during pregnancy is a common practice that has been increasing in recent years. The aim of this study is to describe medication use among pregnant women from the 2015 Pelotas (Brazil) Birth Cohort Study. Methods: This paper relies on a population-based cohort study including 4270 women. Participants completed a questionnaire about the antenatal period, including information about medication use. We performed descriptive analyses of the sample and the medications used and adjusted analyses for the use of medications and self-medication. Results: The prevalence of medication use was 92.5% (95% CI 91.7&ndash, 93.3), excluding iron salts, folic acid, vitamins, and other minerals. The prevalence of self-medication was 27.7% (95% CI 26.3&ndash, 29.1). In the adjusted analysis, women who had three or more health problems during pregnancy demonstrated higher use of medicines. Self-medication was higher in lower income groups and among smokers and multiparous women (three pregnancies or more). Acetaminophen, scopolamine, and dimenhydrinate were the medications most commonly used. Conclusions: This study describes the pattern of drug use among pregnant women in a population-based cohort study, with a high prevalence of self-medication. Greater awareness of the risks of self-medication during pregnancy is required, focusing on groups more prone to this practice, as well as ensuring qualified multidisciplinary prenatal care.

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.

Vestibular migraine (VM) is one of the most debilitating chronic diseases that is currently underdiagnosed and undertreated. The treatment of VM is a dynamic and rapidly advancing area of research. New developments in this field have the potential to improve the diagnosis and provide more individualized treatments for this condition. In this review, we discussed the progress of evidence-based treatment of VM, including pharmacotherapy and nonmedical methods. A search of the literature was conducted up to September 2019. In order to control or cure VM, patients should follow three steps. First, patients should comply with diet and behavioral medication; Second, during the attack of VM, patients should take medicine to control the symptoms. These acute attack treatment of VM consists of antiemetic medications (e.g., dimenhydrinate and benzodiazepines), anti-vertigo medicine, and analgesics (e.g. triptans). Third, prophylactic medicine (e.g., propranolol, topiramate, valproic aid, lamotrigine, and flunarizine) can be used to reduce the frequency and severity of VM attack. Also, vestibular rehabilitation (VR) treatment should be considered for all VM. Meanwhile, we also propose to establish a culture of prevention which is essential for reducing the personal, social and economic burden of VM.

Introduction: Vertigo appears as a result of a sudden neural activity imbalance of the vestibular system. The vertigo prevalence is higher in patients over 60 years of age compared to patients under 40 years of age. Objectives: The purpose of this study was to analyze the effect of craniosacral osteopathy on dizziness and balance in individuals who have peripheral vestibular pathology. Methods: A total of 30 individuals, aged 24–50 years, participated in this study. Twenty-four of the participants were female (80%) and 6 were male (20%). The participants were separated into 2 groups, with 15 patients included in the cranial osteopathy treatment group (study group) and 15 patients included in the group that used dimenhydrinate (control group). The individuals were evaluated in terms of dizziness and balance. A visual analog scale was used to evaluate dizziness. Balance was evaluated using the Berg balance scale and the Activities-Specific Balance Confidence scale. The craniosacral treatment program was applied once per week for 6 sessions. All of the individuals included in this study were evaluated 3 times, i.e., prior to treatment, on the third week of treatment, and on the sixth week of treatment. Results: Significant improvement was noted within each group in terms of dizziness and balance (p < 0.05). When the groups were compared with each other, it was observed that craniosacral osteopathy was more effective than dimenhydrinate treatment for dizziness and balance (p < 0.05). Conclusion: Craniosacral osteopathy is an effective treatment choice in individuals who have chronic peripheral vestibular pathology. In individuals who have resistant and chronic vestibular pathology, craniosacral osteopathy should be evaluated among the treatment choices.

Reporting of intoxication and withdrawal from aberrant use of over-the-counter medication has been sparse and inconsistent in literature. Attributed to their anticholinergic properties, medications such as dimenhydrinate (Gravol) taken in supratherapeutic doses have been associated with euphoria, anxiolysis, and hallucinations. We present a case of a woman in her forties, with a psychiatric history of bipolar disorder, and complex concurrent medical history including familial Mediterranean fever (FMF), and fibromyalgia, admitted for withdrawal management of her intravenous dimenhydrinate use. As a result of her FMF, there were numerous hospital admissions and treatment which required intravenous access. Hence, a physician-inserted intravenous access port was placed on her chest. The port was maintained monthly with the help of a community agency. In this port, she was injecting 100 to 200 mg of dimenhydrinate hourly for its euphoric and calming effects, consuming upwards of 2400 mg/d. Comprehensive laboratory work-up and urine drug screening were unremarkable. Vital signs were stable. Her mental status at time of admission was lethargic, unfocused, but calm. Her withdrawal symptoms included severe nausea, vomiting, sedation, headaches, dizziness, anxiety, and muscle stiffness. Her detoxification was managed with benztropine and lorazepam, and was well tolerated. The patient was discharged to a community inpatient rehabilitation center. Urine drug testing before discharge was negative. This case draws attention to the addictive potential of dimenhydrinate and offers a regime for its medical withdrawal management. Additionally, this case highlights that screening and management of over-the-counter medications warrants further clinical consideration and investigation.

Objetivo: Analisar os riscos potenciais às Gestantes e Fetos, causados pela automedicação de anti-inflamatórios não esteroides. Métodos: A proposta de metodologia para esta pesquisa segue uma estratégia de revisão de literatura, pesquisa exploratória e descritiva, cuja coleta fora realizada em diferentes bases de dados, tais como Scientific Electronic Library Online (SCIELO), registros tanto da Biblioteca Virtual em Saúde (BVS), quanto registros da Medical Literature Analysis and Retrievel System Online (MEDLINE/PUBMED). A busca se deu através do uso dos descritores “AUTOMEDICAÇÃO”; “GESTANTES”, “AINES” e “RISCOS”. Resultados: Percebeu-se que a utilização de medicamentos durante a gravidez pela prática da automedicação com Ibuprofeno 9 (27%), Dipirona 6 (18%), Bromoprida 2 (6%), Paracetamol 13 (40%), Dimenidrinato 3 (9%), sendo 31 (94%) em forma de comprimidos foi relatada por 27 (33,75%) gestantes, e 3 (11,1%) que apresentaram queixas de uso como cefaleia, êmese e náuseas e a indicação foi relatada por 2 (6%) gestantes pela a mãe e as demais por conta própria. Conclusão: Após a análise de diversos artigos científicos, o que fica bem explicito é que, o uso de anti-inflamatórios não esteroidais no início da gravidez não demonstrou ser um fator de risco, porém, após o primeiro trimestre pode ser fatal, tanto para a ocorrência de malformações congênitas estruturais no feto, quanto para problemas renais. Em se tratando da Mãe percebe-se que os AINEs podem prolongar seu tempo de parto, causar hemorragias e enfraquecer seus óvulos para uma futura reprodução.

Dimenhydrinate is an over-the-counter medication that is used to relieve nausea, vomiting, and vertigo caused by motion sickness. It has a short elimination half-life, possibly due to its first-pass metabolism. The current study aimed to prepare and evaluate new transdermal formulations of dimenhydrinate to prolong the drug’s release and improve its cutaneous permeation. First, the patches were fabricated and evaluated to determine their properties. The results were statistically investigated and considered significant at the p &lt, 0.05 level. Additionally, the quantitative analysis of the drug-release data and kinetic modeling was performed by using the DDSolver software to decide the candidate formula dependably. The effect of the penetration enhancers on the permeability of dimenhydrinate from the selected patch was then studied ex vivo compared to the control sample, and the patch’s safety was evaluated in rabbits, using the skin-irritation test.

Vestibular rehabilitation using individualized vibrotactile neurofeedback training (IVNT) can lead to significant improvement in the postural stability of patients with vestibular symptoms of different origins. However, some of these patients have complex, severe dizziness, meaning that a pharmacological pretreatment or parallel (to vestibular rehabilitation) treatment can help them perform the rehabilitation exercises. Hence, the present study investigated the influence of a pharmacological treatment on the efficacy of vibrotactile neurofeedback training in patients with chronic, noncompensated vestibulopathies. All participants performed IVNT for ∼10 min each day for 2 weeks. In addition, every second participant was selected randomly to receive oral medication (20 mg cinnarizine and 40 mg dimenhydrinate per tablet), taking three tables per day. Trunk and ankle sway and postural stability were measured. In addition, the dizziness handicap inventory was evaluated immediately before training on the last day of training and 6 months after training. After the 10-day period of IVNT, both groups showed a statistically significant improvement in all parameters tested. A follow-up analysis after 6 months showed a long-term efficacy for the IVNT, that is, the patients remained significantly improved in their postural stability. The antivertiginous therapy did not hinder the efficacy of the IVNT. The present results indicate that IVNT even in combination with an antivertiginous drug therapy is an effective treatment regime for patients with disabling vertigo of different origins.

Objective It has long been suggested that antivertiginous medications exert their symptomatic effect through inhibition of the vestibulo-ocular reflex (VOR). We tested this hypothesis by directly measuring the VOR after administration of three agents from different substance classes: an antihistamine, a benzodiazepine and a calcium channel antagonist. Methods The gain and the variability of the high velocity VOR was assessed using video head impulses (vHIT) under the following conditions: baseline, after dimenhydrinate, after diazepam and after cinnarizine. Results We found that all three medications did not change any VOR gain or variability parameter: At 60 ms, the gain was 0.95 at baseline, 0.99 under dimenhydrinate, 0.99 under diazepam and 0.96 under cinnarizine. The gain variability across repetitive head impulses remained also uninfluenced. Conclusions The human high frequency VOR remains robust to pharmacological perturbations at common clinical doses and the assumption that symptomatic vertigo relief is achieved merely through impairment of the VOR requires re-examination. Significance Alternative mechanisms of pharmacological action might be operant, such as the modulation of vestibulo-cortical pathways, a differential effect on the low frequency VOR and an altered sensitivity to drugs in acute unilateral vestibulopathy.

Cinnarizine, is approved for nausea, vomiting, motion sickness, inner ear disorders and is considered as first-line pharmacotherapy for management of vertigo. It acts by anti-vasoconstrictor activity, reducing blood viscosity and reducing nystagmus in labyrinth. Lack of adequate literature on clinical evidence of cinnarizine and its combination (dimenhydrinate) in vertigo management prompted this review. A specific MEDLINE literature search strategy was designed combining Medical Subject Headings, free-text keywords (like cinnarizine and vertigo) using Boolean operators (1970–2016) for clinical studies, clinical reviews and meta-analyses of cinnarizine. Analyses of studies validated cinnarizine’s efficacy in peripheral and central vertigo versus placebo or other therapies, and was well-tolerated by the patients recruited across different studies. Cinnarizine and/ or its combinations are favorable in management of vestibular disorders wherein cinnarizine acts predominantly peripherally on labyrinth and dimenhydrinate acts centrally on vestibular nuclei and associated centers in brainstem. Combination therapy of cinnarizine and/ or its combinations demonstrated a better safety profile than either of the mono-components, offering a viable therapeutic option in vertigo management.

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.

OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular system disease causing dizziness. It occurs more in the 5th decade of life and affects the posterior canal in 90% of the patients. The most effective treatment method is canalith repositioning (CRP) maneuver. The aim of this study is to evaluate the effects of betahistine and dimenhydrinate therapies in addition to CRP maneuver on BPPV patients. METHODS: The study included 64 patients who had complaints of dizziness and were diagnosed with BPPV by their history and provocation maneuvers. The patients were divided into two groups. In Group 1, only repositioning maneuver was performed. Group 2 was divided into two subgroups. In Group 2a, repositioning maneuver was performed and betahistine 24 mg twice daily was given for 10 days. In Group 2b, repositioning maneuver was performed and dimenhydrinate 50 mg once daily was given for five days. On the 10(th) day, all patients were reexamined, and provocation maneuver was performed. Dizziness handicap inventory (DHI) was completed and outcomes were reviewed for therapeutic efficacy. RESULTS: Mean DHI scores in all patient groups statistically significantly decreased from a pre-treatment level of 52.16 (range, 20–100) to a post-treatment level of 17.84 (range, 0–78) (p

Introducción: los fármacos con potencial efecto anticolinérgico son prescritos frecuentemente en la población mayor de 65 años. Existen varias escalas para calcular la carga anticolinérgica: Anticholinergic Drug Scale, Anticholinergic Risk Scale y Anticholinergic Cognitive Burden. Objetivo: caracterizar la carga anticolinérgica en pacientes mayores de 65 años con polifarmacia que son formulados ambulatoriamente. Métodos: estudio de corte transversal, retrospectivo con información de prescripción registrada desde abril hasta septiembre de 2016. Se utilizó la base de datos transaccional de prescripción de una EPS nacional registrada en la plataforma tecnológica de un PBM (Pharmacy Benefit Management). Se analizaron los medicamentos con propiedades anticolinérgicas y carga anticolinérgica. Resultados: fueron 115.713 los pacientes formulados, con una edad media de 74 años. Los grupos terapéuticos más asociados con carga anticolinérgica moderada fueron, en un 6,5 %, dimenhidrinato, amantadina, biperideno y quetiapina. Un 13,1 % con carga anticolinérgica alta donde se encuentran el butil bromuro de hioscina y la amitriptilina. Discusión: el manejo de las patologías en los pacientes adultos mayores es compleja y se llega hasta el punto de requerir prescripción de múltiples medicamentos; por lo cual, se hace fundamental evaluar la necesidad del uso de estos, además de verificar su pertinencia y las posibles interacciones farmacológicas de alta significancia clínica, para evitar la presencia de eventos adversos. Por esto se han desarrollado escalas que permiten mejorar el resultado terapéutico especialmente en fármacos con carga anticolinérgica. Background: Drugs with potential anticholinergic effect are usually prescribed to the population over 65 years. There are several scales created to calculate anticholi-nergic burden: Anticholinergic Drug Scale, Anticholi-nergic Risk Scale, and Anticholinergic Cognitive Burden.Objective: To characterize the anticholinergic burden in patients older than 65 years with polypharmacy who are prescribed in ambulatory settings.Methods: Retrospective cross-sectional study with in-formation registered from April to September 2016. The database of prescription records of a health mana-gement organization (HMO), with national registries in the Pharmacy Benefit Management (PBM) technology platform, was used. Medicines were analyzed by its an-ticholinergic properties and anticholinergic burden.Results: There were 115,713 patients with a median age of 74 years. The medicines with moderate anti-cholinergic burden were dimenhydrinate, amantadi-ne, biperidene and quetiapine in 6.5 %, and with high anticholinergic burden hyoscine butylbromide and amitryptiline in 13.1 %.Discussion: The medical attention of diseases of the el-derly is complex and requires the prescription of multiple medications. It is important to evaluate the medicines and verify their relevance and possible pharmacologi-cal interactions, to avoid the presence of adverse events. For this reason, scales have been developed, they allow improving therapeutic results, and especially in medici-nes with anticholinergic burden and systems of clinical alerts that promotes correct formulation.

Objective Seasickness is a widespread problem among naval crew, and has a major impact on their performance at sea. The three pharmacological agents most commonly employed in the treatment of seasickness are dimenhydrinate, cinnarizine, and scopolamine. At present, the effectiveness of anti-seasickness drugs is tested by a process of “trial and error”, while sailing and exposed to sea conditions. A physiological test to evaluate the action of a drug might save crew members long periods of suffering, as well as simplifying the procedure of selecting the appropriate treatment for each individual. The cervical vestibular evoked myogenic potentials (cVEMP) test has come to be recognized as a reliable procedure for the objective evaluation of saccular function. It was the hypothesis of the present study that cVEMP otolith responses may be affected by anti-motion sickness drugs, which might thus make cVEMP a useful clinical neurophysiological tool for the assessment of drug absorption and efficacy. Methods Thirty male sailors who regularly took medication for the treatment of seasickness participated in the study. Participants underwent the cVEMP test pre- and 1 h post-drug administration. Results A statistically significant decrease in p13 latency was found after administration of scopolamine compared with baseline (14.46 ms vs. 15.09 ms, p = 0.0049), with significant prolongation of the binaural average inter-latency in this group. No differences were found in the dimenhydrinate and cinnarizine study groups. Conclusions This study demonstrated that scopolamine absorption can be verified by changes in cVEMP latencies. Significance The potential of the cVEMP test for predicting action of scopolamine on the vestibular system.

Background Paroxysmal movement disorders including paroxysmal tonic upward gaze of infancy and paroxysmal dystonia of infancy are benign but uncommon movement disorders seen in young children. Although symptoms are intermittent and resolve spontaneously, they can cause discomfort and distress for the child. Current treatment options are limited to dopaminergic agents or anticonvulsants with limited efficacy. Patient Description The authors present a child with paroxysmal tonic upward gaze of infancy and another with paroxysmal dystonia of infancy, both of whom responded successfully to treatment with low-dose dimenhydrinate or diphenhydramine, respectively. Discussion Dimenhydrinate and diphenhydramine both exert anticholinergic activity and have limited toxicity at low doses. This property makes either compound an attractive therapeutic option for paroxysmal movement disorders in infancy. These agents are generally well tolerated.

Objectives: One of the major causes of mortality in children is acute gastroenteritis. Vomiting is common in early stages of the disease. The aim of this study was to determine the effect of oral dimenhydrinate (DH) in the control of vomiting in cases of acute gastroenteritis in children. Methods: This double-blind, randomized, clinical trial was conducted in a university-affiliated hospital in a western province of Iran. Two hundred children aged one to 12 years old were randomly assigned to either drug or placebo groups. Children in the drug group received oral DH as four doses of 1 mg/kg every six hours (maximum 200 mg), and children in the placebo group received a placebo drug. The patients variables were compared 24 hours after receiving the first dose and at seven and 14 days after discharge. Results: The mean number of episodes of vomiting was 4.4±2.5 in the drug group versus 4.4±2.1 in the placebo group, which was not statistically significant (p0.050). Conclusions: Oral DH in children with acute gastroenteritis does not reduce the number and duration of vomiting. However, our results showed that consumption of DH in acute gastroenteritis patients was effective in reducing the frequency and duration of diarrhea and further investigation into this is warranted.

Background: The treatment of benign paroxysmal positional vertigo (BPPV) has not been well studied. Many clinicians are indifferent about canalith reposition maneuvers and frequently prefer medical treatments. Objectives: We aimed to detect efficacy of Epley maneuver in relieving symptoms of benign paroxysmal positional vertigo patients diagnosed in emergency department and if medical treatments are useful in patients whose symptoms were not relieved. Methods: The study was conducted as a prospective cohort study in the emergency department of a tertiary hospital. Patients who were over 18 years of age and presented to emergency department with complaints of vertigo symptoms and nausea and had a positive Dix–Hallpike test were included in the study. Patients’ demographic data, possible etiological factors, affected ear, and benign paroxysmal positional vertigo diagnosis in the history were recorded on the study data form. The European Evaluation of Vertigo scale and the Visual Analogue Scale (VAS) score of nausea and vertigo symptoms were graded and recorded for each patient before and after treatment. Results: Ninety patients were included in the study in total. Epley maneuver was carried out to all patients. Vertigo symptoms VAS (VASd) score (p nv) score (p d (p = 0.048), VASnv (p = 0.031), and European Evaluation of Vertigo scale scores (p = 0.001) at a statistically significant level more than dimenhydrinate treatment alone. Conclusions: Epley maneuver may be applied to every patient with benign paroxysmal positional vertigo. Dimenhydrinate and/or metoclopramide helps to control patients’ symptoms whose symptoms remain despite Epley maneuver.

BackgroundBenzodiazepines and sedative hypnotics (BSH) have numerous adverse effects that can lead to negative outcomes, particularly in vulnerable hospitalised older adults. At our institution, over 15% of hospitalised older adults are prescribed sedative-hypnotics inappropriately. Of these prescriptions, 87% occurred at night to treat insomnia and almost 20% came from standard admission order sets.MethodsWe conducted a time-series study from January 2015 to August 2016 among medical and cardiology inpatients following the implementation in August 2015 of a sedative reduction bundle (education, removal of BSH from available admission order sets and non-pharmacological strategies to improve sleep). Preintervention period was January–July 2015 and postintervention period was August 2015–August 2016. A surgical ward served as control. Primary outcome was the proportion of BSH-naive (not on BSH prior to admission) patients 65 years or older discharged from medical and cardiology wards who were prescribed any new BSH for sleep in hospital. Data were analysed on statistical process control (SPC) p-charts with upper and lower limits set at 3δ using standard rules. Secondary measures included Patient-reported Median Sleep Quality scores and rates of fall and sedating drug prescriptions that may be used for sleep (dimenhydrinate).ResultsDuring the study period, there were 5805 and 1115 discharges from the intervention and control units, respectively. From the mean baseline BSH prescription rate of 15.8%, the postintervention period saw an absolute reduction of 8.0% (95% CI 5.6% to 10.3%; pConclusionA comprehensive intervention bundle was associated with a reduction in inappropriate BSH prescriptions among older inpatients.

Histamine type-1 (H1) receptor antagonists such as diphenhydramine are frequently used for treatment of pruritus in dogs, yet therapeutic efficacy for allergic disorders is reported to be highly variable. Dimenhydrinate is a salt of diphenhydramine and 8-chlorotheophylline, and has been reported to produce superior oral absorption of diphenhydramine.To determine the pharmacokinetic and pharmacodynamic properties of diphenhydramine in dogs after intravenous (1 mg/kg) and oral (5 mg/kg) administration, and when given orally as dimenhydrinate at a dose of 10 mg/kg (≈5 mg/kg diphenhydramine).Each drug was administered to six healthy, fasted mixed-breed dogs in a research facility, using a cross-over design.Blood samples were collected for pharmacokinetic analysis of diphenhydramine and chlorotheophylline at defined intervals. Pharmacodynamic response was measured by histamine-mediated cutaneous wheal formation.There was great variability in the data and one dog was an extreme outlier. The mean systemic availabilities of diphenhydramine were 7.8% and 22.0% after oral administration of diphenhydramine and dimenhydrinate, respectively, whereas the mean maximum concentrations were 36 (± 20) and 124 (± 46) ng/mL. The terminal elimination half-lives of diphenhydramine and dimenhydrinate were 5.0 (± 7.1) and 11.6 (± 17.7) h, respectively. Plasma diphenhydramine concentrations did not correlate with the percentage reduction in histamine-induced wheal formation. Theophylline reached plasma concentrations considered to be therapeutic for dogs.Oral absorption of diphenhydramine was approximately three times greater with a longer half-life when it was administered as the combination product dimenhydrinate.Les antihistaminiques de type 1 (H1) tels que la diphénhydramine sont fréquemment utilisés pour le traitement du prurit chez le chien, bien que l'efficacité thérapeutique pour les troubles allergiques rapportée soit hautement variable. Le diménhydrinate est un sel de diphénhydramine et de 8-chlorothéophylline décrit comme ayant une meilleur absorption orale que la diphénhydramine. HYPOTHÈSES/OBJECTIFS: Déterminer les propriétés pharmacocinétiques et pharmacodynamiques de la diphénhydramine des chiens après administration intraveineuse (1mg/kg) et orale (5 mg/kg) et lorsque donné oralement sous forme de diménhydrinate à la dose de 10 mg/kg (≈5 mg/kg diphénhydramine).Chaque médicament a été administré à jeun à six chiens croisés sains dans un centre de recherche avec une étude croisée. MATÉRIEL ET MÉTHODE: Des échantillons sanguins ont été prélevés pour analyse pharmacocinétique de diphénhydramine et chlorothéophylline à des intervalles définis. La réponse pharmacocinétique a été mesurée par la formation de plaques cutanées médiées par l'histamine. RÉSULTATS: Il y avait une grande variabilité des données et un chien présentait des valeurs extrèmes non exploitables. Les disponibilités moyennes de diphénhydramine étaient 7,8% et 22,0% après administration orale respectivement de diphénhydramine et diménhydrinate tandis que les concentrations maximales moyennes étaient 36 (± 20) et 124 (± 46) ng/mL. Les demi-vies d’élimination terminales de diphénhydramine et diménhydrinate étaient respectivement 5.0 (± 7.1) et 11.6 (± 17.7) h. Les concentrations plasmatiques de diphénhydramine ne corrélaient pas avec la diminution de pourcentage de la formation de plaque liée à l'histamine. Les concentrations plasmatiques atteintes par la théophylline sont considérées comme thérapeutiques chez le chien.L'absorption orale de diphénhydramine était approximativement trois fois plus importante avec une demi-vie plus longue quand administrée comme combiné de diménhydrinate.INTRODUCCIÓN: los antagonistas de los receptores de histamina tipo 1 (H1), como la difenhidramina, se utilizan con frecuencia para el tratamiento del prurito en perros, aunque se indica que la eficacia terapéutica para los trastornos alérgicos es muy variable. Dimenhidrinato es una sal de difenhidramina y 8-cloroteofilina, y se ha publicado que tiene una absorción oral superior de difenhidramina. HIPÓTESIS/OBJETIVO: determinar las propiedades farmacocinéticas y farmacodinámicas de la difenhidramina en perros después de la administración intravenosa (1 mg/kg) y oral (5 mg/kg), y cuando se administra por vía oral como dimenhidrinato en una dosis de 10 mg/kg (5 mg/kg de difenhidramina). ANIMALES: cada medicamento se administró a seis perros sanos, de raza mestiza en un centro de investigación, utilizando un método de estudio cruzado. MÉTODOS Y MATERIALES: se recogieron muestras de sangre para el análisis farmacocinético de la difenhidramina y la cloroteofilina a intervalos definidos. La respuesta farmacodinámica se midió mediante formación de abones cutáneos mediadas por histamina. RESULTADOS: hubo una gran variabilidad en los datos y un perro fue un caso atípico extremo. La disponibilidad sistémica media de la difenhidramina fue de 7,8% y 22,0% después de la administración oral de difenhidramina y dimenhidrinato, respectivamente, mientras que las concentraciones máximas promedio fueron de 36 (± 20) y 124 (± 46) ng/mL. Las vidas medias de eliminación terminal de la difenhidramina y el dimenhidrinato fueron de 5,0 (± 7,1) y 11,6 (± 17,7) h, respectivamente. Las concentraciones de difenhidramina en plasma no se correlacionaron con el porcentaje de reducción en la formación de abones inducidos por histamina. La teofilina alcanzó concentraciones plasmáticas consideradas terapéuticas para perros. CONCLUSIÓN: la absorción oral de difenhidramina fue aproximadamente tres veces mayor con una vida media más larga cuando se administró como el producto de combinación dimenhidrinato.Histamin Typ-1 (H1) Rezeptor Antagonisten, wie Diphenhydramin werden häufig zur Behandlung von Juckreiz bei Hunden eingesetzt, ihre therapeutische Wirksamkeit bei allergischen Erkrankungen wird als höchst unterschiedlich beschrieben. Demenhydrinat ist ein Salz des Diphenhydramins und 8-Chlorotheophyllins. Es gibt Berichte, dass es die per os Absoprtion von Diphenhydramin stark verbessert.Eine Feststellung der pharmakokinetischen und pharmakodynamischen Eigenschaften von Diphenhydramin bei Hunden nach intravenöser Verabreichung (1 mg/kg) sowie einer Verabreichung per os (5 mg/kg), sowie eine per os Verabreichung als Dimenhydrat bei einer Dosis von 10 mg/kg (≈5 mg/kg Diphenhydramin).Jedes Medikament wurde sechs gesunden, nüchternen Mischlingshunden in einer Versuchsanstalt unter Verwendung eines Cross-over Designs verabreicht.Es wurden Blutproben zur pharmakokinetischen Analyse von Diphenhydramin und Chlorotheophyllin in definierten Intervallen genommen. Die pharmakodynamische Antwort wurde mittels Histamin-mediierter kutaner Quaddelbildung gemessen.Es bestand eine große Variabilität bei den Daten und ein Hund stellte einen extremen Ausreißer dar. Die durchschnittlichen systemischen Verfügbarkeiten von Diphenhydramin waren 7,8% und 22,0% nach einer per os Verabreichung von Diphenhydramin bzw Dimenhydrinat, während die durchschnittlichen maximalen Konzentrationen 36 (± 20) und 124 (± 46) ng/mL betrugen. Die terminalen Halbwertszeiten der Elimination von Diphenhydramin bzw Dimenhydrinat waren 5,0 (± 7,1) bzw 11,6 (± 17,7). Die Diphenhydramin Konzentrationen im Plasma korrelierten nicht mit der prozentualen Reduzierung der Histamin-induzierten Quaddelbildung. Das Theophyllin erreichte Plasmakonzentrationen, die als therapeutisch für Hunde angesehen werden.Die per os Absorption von Diphenhydramin war etwa dreimal größer mit einer längeren Halbwertszeit als eine Verabreichung im Kombinationsprodukt Dimenhydrinat.背景: 组胺1型(H1)受体拮抗剂,如苯海拉明,常用于治疗犬的瘙痒,但有报道称,对过敏性疾病的治疗效果非常不确定。茶苯海明是苯海拉明和8-氯代茶碱的一种盐,据报道,其产生能被较好口服吸收的苯海拉明。 假设/目的: 确定犬静脉注射(1 mg/kg)和口服(5 mg/kg)苯海拉明后的药代动力学和药效学特性,并以10 mg/kg的剂量口服给予茶苯海明(≈5mg/kg苯海拉明)。 动物: 将每种药物通过交叉设计,给予六只研究所内健康、禁食的杂种犬。 方法和材料: 采集血液样本,以规定的间隔对苯海拉明和茶碱进行药代动力学分析。通过组胺介导形成皮肤风疹,测量药效学反应。 结果: 数据有很大的可变性,一只犬有极端异常值。口服苯海拉明和茶苯海明后,苯海拉明的平均全身可用量分别为7.8%和22.0%,而平均最大浓度分别为36(±20)和124(±46)ng/mL。苯海拉明和茶苯海明的终末消除半衰期分别为5.0(±7.1)和11.6(±17.7)h。血浆苯海拉明浓度与组胺诱导的风疹减少百分比无关。茶碱达到被认为对犬有治疗作用的血浆浓度。 结论: 茶苯海明当作为组合产品给药时,其口服吸收半衰期较长,大约是口服苯海拉明的三倍。.Os antagonistas de receptores histamínicos do tipo-1 (H1) como a difenidramina são utilizados frequentemente no tratamento do prurido em cães, ainda que a eficácia terapêutica no tratamento de alergopatias seja relatada como altamente variável. O dimenidrinato é um sal da difenidramina e 8-cloroteofilina, e relatos sugerem que este possui absorção oral superior à da difenidramina. HIPÓTESE/OBJETIVO: Determinar as propriedades farmacocinéticas e farmacodinâmicas da difenidramina em cães após administração intravenosa (1 mg/kg) e oral (5 mg/kg), e quando administrado por via oral como dimenidrinato em uma dose de 10 mg/kg (≈5 mg/kg difenidramina).Cada fármaco foi administrado a seis cães mestiços saudáveis de um centro de pesquisa, em jejum, utilizando um delineamento experimental cruzado. MÉTODOS E MATERIAIS: Amostras de sangue foram coletadas para análise farmacocinética de difenidramina e cloroteofilina em intervalos definidos. A resposta farmacocinética foi mensurada pela formação de pápulas mediadas por histamina na pele.Houve uma grande variação nos dados e um cão destoou extremamente dos demais, sendo considerado um ponto fora da curva (outlier).A média das disponibilidades sistêmicas de difenidramina foram 7,8%e 22,0% após administração de difenidramina e dimenidrinato, respectivamente, enquanto as concentrações máximas médias foram 36 (± 20) e 124 (± 46) ng/mL. As meias-vidas de eliminação terminal de difenidramina e dimenidrinato foram 5,0 (± 7,1) e 11,6 (± 17,7) h, respectivamente. As concentrações plasmáticas de difenidramina não correlacionaram com a porcentagem de redução na formação de pápulas induzidas por histamina. A teofilina alcançou concentrações consideradas terapêuticas para cães. CONCLUSÃO: A absorção oral de difenidramina foi aproximadamente três vezes maior com uma meia-vida mais longa quando administrada em combinação com o produto dimenidrinato.背景: ジフェンヒドラミンなどのヒスタミン1型(H1)受容体拮抗薬は、犬の掻痒治療に頻繁に使用されるが、それでもアレルギー性疾患に対する治療効果は非常に変動的であると報告されている。ジメンヒドリナートはジフェンヒドラミンおよび8-クロロテオフィリンの塩であり、ジフェンヒドラミンの優れた経口吸収を生じさせることが報告されている。 仮説/目的: 本研究の目的は、ジフェンヒドラミンを 静脈内(1 mg/kg)および経口(5 mg/kg)、ならびにジメンヒドリナートを10mg / kgの用量で経口投与された場合(約5mg / kgのジフェンヒドラミン)の犬におけるジフェンヒドラミンの薬物動態学的および薬力学的特性を決定することである。 被験動物: 研究施設内の6頭の健常な絶食状態の雑種犬に、各薬剤をクロスオーバーデザインによって投与した。 方法および材料: ジフェンヒドラミンおよびクロロテオフィリンの薬物動態解析のため、定義された間隔で血液サンプルを採取した。薬力学的応答は、ヒスタミン媒介皮膚膨疹形成によって測定した。 結果: データには大きなばらつきがあり、1頭の犬が極端な異常値を示した。ジフェンヒドラミンおよびジメンヒドリナートの経口投与後のジフェンヒドラミンの平均全身アベイラビリティはそれぞれ7.8%と22.0%であったが、平均最高濃度は36(±20)と124(±46)ng / mLであった。ジフェンヒドラミンおよびジメンヒドリナートの消失半減期はそれぞれ5.0(±7.1)と11.6(±17.7)hであった。血漿ジフェンヒドラミン濃度は、ヒスタミン誘発性膨疹形成の減少率と相関しなかった。テオフィリンは、犬の治療に役立つと考えられる血漿濃度に達した。 結論: ジフェンヒドラミンをコンビネーションプロダクトであるジメンヒドリナートとして投与した場合、ジフェンヒドラミンの経口吸収は約3倍大きく、より長い半減期を有した。.

Background Seasickness and travel sickness are classic types of motion illness. Modern simulation systems and virtual reality representations can also induce comparable symptoms. Such manifestations can be alleviated or prevented by various measures. Methods This review is based on pertinent publications retrieved by a PubMed search, with special attention to clinical trials and review articles. Results Individuals vary in their susceptibility to autonomic symptoms, ranging from fatigue to massive vomiting, induced by passive movement at relatively low frequencies (0.2 to 0.4 Hz) in situations without any visual reference to the horizontal plane. Younger persons and women are considered more susceptible, and twin studies have revealed a genetic component as well. The various types of motion sickness are adequately explained by the intersensory conflict model, incorporating the vestibular, visual, and proprioceptive systems and extended to include consideration of postural instability and asymmetry of the otolith organs. Scopolamine and H1-antihistamines, such as dimenhydrinate and cinnarizine, can be used as pharmacotherapy. The symptoms can also be alleviated by habituation through long exposure or by the diminution of vestibular stimuli. Conclusion The various types of motion sickness can be treated with general measures to lessen the intersensory conflict, behavioral changes, and drugs.

Introduction and Background: Vertigo is a medical condition where a person feels as he/ she or the objects around them are moving when they are stable and not moving. Antihistamines, Calcium antagonists, histamine analogs (eg, betahistine derivatives), diuretics, neuroleptics as well as other psychotherapeutic drugs, corticosteroids agents and hemorheologics can be used for the treatment of Vertigo. Combination of Cinnarizine which is a selective calcium-channel blocker and Dimenhydrinate which is an H 1 antihistaminic drug can be used in combination for the treatment of vertigo. This clinical study was conducted to evaluate the efficacy and safety of combination of Cinnarizine 20 mg and Dimenhydrinate 40 mg in patients of vertigo of age group 18 to 65 years. Methodology: Out of total 216 patients, 168 completed the study. Efficacy assessment was made by analysing the reduction in vertigo symptom score (VSS). Safety assessment was made by analysing the adverse events experienced by the patient or observed by the investigator during trial. Results: Reduction in VSS from 7.277 (baseline) to 3.975 (day 3) and 0.987 (day 5). At visit 2 and visit 3 there was reduction of 45.373 % and 86.426 % in mean VSS score. Conclusion: A combination of Cinnarizine 20 mg and Dimenhydrinate 40 mg is safe and efficacious in the treatment of vertigo.

The Side Effects of Drugs Annuals forms a series of volumes in which the adverse effects of drugs, clinically significant drug interactions, pharmacogenetic variations of drug metabolism and new pharmacokinetic discoveries are reported. This series supplements the contents of Meyler’s Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. This review from January 2016 to December 2016 contains a brief synopsis and references for adverse reactions to antihistamines: bilastine, chlorpheniramine, cyproheptadine, dimenhydrinate, ketotifen, levocetirizine, rupatadine.

Dimenhydrinate (DMH)-loaded buccal bioadhesive films for the prevention and treatment of motion sickness were prepared and optimized. This study examines the rate of drug release from the films for prolonged periods of time to reduce or limit the frequency of DMH administration. Based on preliminary studies using various polymers and concentrations, hydroxyethylcellulose (2.5, 3.0, and 3.2%), and xanthan gum (2.8%) were chosen as matrix polymers. The films were analyzed with respect to their mechanical, physicochemical, bioadhesive, swelling, and in-vitro release properties. In in-vivo pharmacokinetic studies, xanthan gum-based DMH buccal film was associated with significantly increased DMH plasma levels between 1 h and 5 h after DMH dosing when compared with an oral drug solution. The area under the curve AUC0-7 h value of the mucoadhesive buccal film was two-fold higher than the oral DMH solution. Histological analysis revealed that DMH films cause mild morphological and inflammatory changes in rabbit buccal mucosa. The DMH buccal film is effective for approximately 7 h, thus representing an option for single-dose antiemetic therapy. This dosage regimen could be particularly beneficial for chain travelers who travel for long periods of time.

Vestibular migraine (VM) is one of the most frequent causes of episodic vertigo, with a lifetime prevalence of 0.98 %. Prophylactic therapy includes calcium channel blockers, beta-blockers, antiepileptic drugs and antidepressants. We studied the association of cinnarizine 20 mg and dimenhydrinate 40 mg (Arlevertan©) in a group of 22 patients affected by definite VM. Proposed therapy included one tablet twice a day for 1 month, which was repeated three times with 1 month of interval between drug intake; results were compared with those of a control group of 11 VM patients who asked to observe only lifestyle measures for migraine. The main outcome was the number of vertigo and headache crises in the 6 months before therapy and in the 6 months of follow-up. Subjects performing Arlevertan© presented during the 6 months of therapy a decrease of vertigo attacks from 5.3 to 2.1 and of headaches from 4.3 to 1.7 (p < 0.0001); 68 % of these subjects reported a decrease of at least 50 % of vertigo attacks, while 63 % of headaches. Conversely, vertigo attacks decreased from 3.5 to 2.2 and headaches from 2.6 to 2 in patients observing only lifestyle; 18 % of these subjects reported a decrease of at least 50 % of vertigo crises and 27 % of headaches. Our data do not differ from those of previous works assessing efficacy of different prophylactic therapies for VM and reporting consistent reduction of vertigo spells in a rate of patients ranging from 60 and 80 %.

1. Kirishanth Perinpanathan, MD* 2. Edward Heilman, MD, FAAD† 3. Haamid Chamdawala, MD, MPH‡ 1. *Department of Family Medicine, The Brooklyn Hospital Center, Brooklyn, NY. 2. †Departments of Dermatology and Pathology, SUNY Downstate Medical Center, Brooklyn, NY. 3. ‡Department of Pediatrics, The Brooklyn Hospital Center, Brooklyn, NY. A 15-year-old previously healthy teen comes to the emergency department with a 2-week history of a generalized pustular rash. The rash initially appeared while she was on a cruise to the Bahamas as multiple red, itchy, raised, pinpoint lesions over her inguinal areas accompanied by a fever. Within the next 24 hours, the rash rapidly progressed to involve her entire body, and both of her feet and ankles swelled. She was evaluated by her pediatrician and prescribed hydroxyzine and hydrocortisone cream, which provided little relief. She visits the emergency department today due to the worsening of her symptoms and is admitted for further evaluation. She reports taking dimenhydrinate for motion sickness 2 days before her rash appeared. She has not been exposed to new soaps or skin emollients. She has no history of any viral illness. She had used the cruise swimming pool but had not swum in the ocean. She has no known drug allergies and no family history of atopic dermatitis or autoimmune disease. On physical examination, she has a temperature of 38.5°C (101.3°F) and is in mild discomfort from the pruritic rash. Skin examination reveals numerous small (pinhead-sized), nonfollicular pustules over a diffuse erythematous and edematous base (Fig 1) accompanied by generalized scaling and active desquamation of the skin (Fig. 2). She has no palpable lymph nodes. There is no mucous membrane involvement and Nikolsky sign is negative on both affected and healthy skin. Figure 1. Numerous …

The phenomenon of stupefying by the use of available over-the-counter drugs (OTC) among adolescents is an essential problem in both Poland and throughout the world. Popular analgesics, cold medicine and antihistamines contain psychedelic substances, such as dextromethorphan (DXM), pseudoephedrine/ephedrine, codeine (methylmorphine), dimenhydrinate, paracetamol (acetaminophren) and others. Cases of fatal addiction to dextromethorphan, one of the active substances contained in medicines, e.g., the common cold, have been reported. The test results cited by the authors clearly indicate that the use of OTC drugs, whose turnover is not controlled is a domain of females. The extent of use of drugs not prescribed by a doctor has remained for many years at a constant level. The most common poisonings with OTC drugs are caused by those that affect the respiratory system or exert analgesic or antipyretic effects. They are also used in attempted suicides, especially among females. Analyzing poisonings caused by OTC medications their seasonality has been observed. Their number increases during spring-autumn. A territorial differentiation in areas of OTC drug trade in terms of their quantities, with the predominance of southern regions is also noted. Intoxication with psychoactive substances causes the deterioration of relations between young people. In the reviewed studies there is no detailed information on the composition of non-prescription medicines. Moreover, young people have easy access to mushroom fungi, growing in nearby forests and meadows that may have hallucinogenic effects and are available in pharmacies and on the Internet. Med Pr 2017;68(3):413-422.Zjawisko odurzania się lekami dostępnymi bez recepty (over-the-counter – OTC) przez młodzież jest problemem obecnym zarówno w Polsce, jak i na świecie. Popularne leki przeciwbólowe, na przeziębienie i przeciwhistaminowe zawierają substancje psychoaktywne, takie jak dekstrometorfan (DXM), pseudoefedryna/efedryna, kodeina (metylomorfina), dimenhydrynat, paracetamol (acetaminofen) i inne. Opisywane są przypadki uzależnienia od dekstrometorfanu, który jest jedną z substancji czynnych leków np. na przeziębienie. Przytoczone przez autorów wyniki badań wskazują jednoznacznie, że używanie leków OTC, którymi obrót nie podlega kontroli, dotyczy głównie płci żeńskiej. Poziom używania leków nieprzepisanych przez lekarza utrzymuje się od wielu lat na stałym poziomie. Najczęściej zatrucia lekami OTC są spowodowane preparatami z grupy tych, które wpływają na układ oddechowy lub działają przeciwbólowo czy przeciwgorączkowo. Wykorzystywane są one również w próbach samobójczych, głównie przez osoby płci żeńskiej. Analiza zatruć lekami OTC ujawniła ich sezonowość – ich liczba wzrasta w okresie wiosenno-letnim. Zauważalne jest zróżnicowane terytorialne, z przewagą terenów południowych, ilości sprzedawanych leków tego typu. Odurzanie się substancjami psychoaktywnymi powoduje pogorszenie relacji między młodymi ludźmi. W analizowanych badaniach brakuje szczegółowych informacji dotyczących składu analizowanych leków dostępnych bez recepty. Ponadto młodzież ma dostęp do grzybów mogących mieć działanie halucynogenne, rosnących w lasach i na łąkach, a także sprzedawanych w sklepach zielarskich i Internecie. Med. Pr. 2017;68(3):413–422.

Introduction: Postoperative Nausea and Vomiting is one of the most common problems after implementation of general anesthesia. The incidence can reach 80% in high-risk patients, depending on the type of surgery. In our study, we aimed to compare dexamethasone–dimenhydrinate and dexamethasone–ondansetron combinations in prevention of nausea and vomiting in postoperative patients. Method: Sixty 18–65-year-olds ASAI-II females who underwent rhinoplasty were included in the study. Patients were randomly included in two groups: Dexamethasone–dimenhydrinate group (group DD) and dexamethasone–ondansetron group (group DO). All patients received dexamethasone 8 mg iv after endotracheal intubation. Anesthesia continuation was established with sevoflurane, air–oxygen mixture and remifentanil infusion. At the 30th minute of the operation, group DO received ondansetron 4 mg iv and group DD received dimenhydrinate 1 mg/kg iv. For postoperative analgesia tramadol (1.5 mg/kg) iv, tenoksikam (20 mg) and afterward for postoperative patient-controlled tramadol was used. In the postoperative recovery room, nausea and vomiting were evaluated at the 30th, 60th, 120th minutes and at the end of 24 h. Total amount of tramadol was recorded. All results were statistically evaluated. Observations: Demographics and Apfel risk scores of both groups were similar. Surgical operation duration (p = 0.038) and total preoperative remifentanil consumption were higher in group DD (p = 0.006). In group DO, nausea at 30 and 60 min (p = 0.001, p = 0.007), retching at 30 and 60 min (p = 0.002, p = 0.006) were higher than group DD. The additional antiemetic need in group DO was significantly higher at 30 min (p = 0.001). Postoperative analgesic consumption was similar in both groups. Result: Our study revealed that dexamethasone–dimenhydrinate combination was more effective than dexamethasone–ondansetron in prevention of nausea and vomiting after rhinoplasty operations. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. © 2016, Springer Science+Business Media New York and International Society of Aesthetic Plastic Surgery.

Objective Evaluating if antiemetics are effective in the prevention or treatment at home, of chemotherapy-induced emesis. Methods In total, were included 42 women with breast cancer in moderately emetogenic chemotherapy, using dexamethasone/ondansetron before each cycle. The frequency of nausea and vomiting was obtained by applying the instrument in the pre-chemotherapy period, and 24h, 48h, 72h and 96h after chemotherapy. The use of antiemetics was considered in accordance with adherence to medical prescription. Results All patients (n = 42, 100%) reported emesis at some point. Only five cases (11.9%) were anticipatory. In the first 24 hours (acute emesis), 38 (90.5%)ayed), emesis was reported by all despite the regular use (n = 20, 47.6%) or not (n = 22, 52.4%) of antiemetics (ondansetron, dexamethasone and metoclopramide/or dimenhydrinate). Conclusion Antiemetics were not effective in the prevention or treatment at home, of chemotherapy-induced emesis. Objetivo : Avaliar se antieméticos são eficazes na prevenção ou tratamento da emese induzida pela quimioterapia antineoplásica, em domicílio. Métodos : Foram incluídas 42 mulheres com câncer de mama, em quimioterapia moderadamente emetogênica, submetidas à dexametasona/ondansetrona antes de cada ciclo. A frequência de náuseas e vômitos foi obtida por instrumento aplicado nos tempos pré-quimioterapia e 24h, 48h, 72h e 96h pós-quimioterapia. O uso de antieméticos foi considerado conforme adesão à prescrição médica. Resultados : Todas as pacientes (n=42, 100%) relataram emese em algum momento. Apenas cinco casos (11,9%) foram antecipatórios. Nas primeiras 24h (emese aguda), 38 (90,5%) apresentaram náuseas associadas (n=20, 47,6%) ou não (n=18, 42,8%) a vômitos e, após este período (tardio), a emese foi referida por todas, apesar da utilização regular (n=20, 47,6%) ou não (n=22, 52,4%) de antieméticos (ondansetrona, dexametasona, metoclopramida e/ou dimenidrinato). Conclusão : Os antieméticos não foram eficazes na prevenção ou no tratamento da emese induzida pela quimioterapia, em domicílio.

Dimenhydrinate, an antihistamine that is used for motion sickness, vertigo and emesis, is abused by drug addicts and psychiatric patients. In the literature, there are case reports about the addict...

Objectives/Hypothesis To investigate the characteristics of residual symptoms and to evaluate the effects of adjuvant vestibular suppressants on residual symptoms after successful canalith repositioning procedures (CRPs). Study Design Individual randomized controlled trial. Methods One hundred fifty patients with idiopathic benign paroxysmal positional vertigo who achieved successful CRPs on initial visit participated in this study. Dizziness Handicap Inventory (DHI) questionnaires were completed before CRPs. All study populations were divided into three groups after successful CRPs on the initial visit day: the medication (V) group (treated with a vestibular suppressant [dimenhydrinate 50 mg per day]), the placebo (P) group, and the no medication (N) group. One week after successful CRPs, residual symptoms were checked and repeated DHI questionnaires were completed to compare residual symptoms. Results Among the 138 patients who did not show positional nystagmus at follow-up, 67 (48.5%) complained of residual symptoms. The presence of residual symptoms was more prevalent in the P and N group compared with the V group (P = .035, P = .017, respectively). The most frequent residual symptom was lightheadedness (n = 42). Moreover, in the V group, lightheadedness was significantly reduced compared with the P group (P = .029). However, in the analysis of DHI, total and subscale scores did not differ across the three groups before or after successful CRP. Conclusions Vestibular suppressants significantly reduced residual symptoms compared to both placebo and no medication after CRP. However, there was no significant reduction in DHI score compared with the control group, suggesting that the residual symptoms could not be evaluated by DHI score alone. Level of Evidence 1b Laryngoscope 124:2400–2403, 2014

OBJECTIVE: The aim of this study is to determine the effects of betahistine and dimenhydrinate on the slow phase velocity. MATERIALS and METHODS: Forty patients with complaints of vertigo and dizziness volunteered to be included in the study. All patients who were included the study were treated at the other medical centers. The patients were divided into two Groups. Patients in the first Group were given betahistine 24 mg three times per day. During this treatment, caloric testing was performed, and the dose was increased to 48 mg three times a day due to ongoing complaints. The test was then repeated four weeks after using this higher dosage. Patients in the second Group had caloric testing while using and four weeks after stopping dimenhydrinate. RESULTS: The study Group was comprised of 40 patients; 20 patients (13 female, 7 male, 18-68 years, median age 46) in the betahistine Group and 20 patients (14 female, 6 male, 24-74 years, median age 44.5) in the dimenhydrinate Group. The average slow phase maximum velocity in the first Group of patients was 18 -/+ 8.2 and 21.1 -/+ 10.8 deg/s at 24 mg betahistine three times a day and 48 mg three times a day, respectively. In the second Group of patients, the average slow phase velocity was 13.4 -/+ 5.1 and 18.2 -/+ 7.5 deg/s during and after stopping the treatment of dimenhydrinate, respectively. The caloric test-induced slow-phase velocity was decreased with dimenhydrinate and increased with the higher dosage of betahistine. CONCLUSION: To our knowledge, this is the first study to demonstrate that betahistine increases caloric-induced slow-phase velocity in humans. Dimenhydrinate and betahistine should not be used together because of their opposite effects on the vestibular system. Dimenhydrinate can be used to treat acute episodes of vertigo, whereas betahistine should not be used during the episode but may be used in the period between the attacks to stimulate the vestibular system. © The Mediterranean Society of Otology and Audiology.

Objective: To report a case of erythema multiforme secondary to dimenhydrinate and pamabrom cross-sensitivity. Case Summary: A 22-year-old Chinese female presented with a complaint of lip mucosal ulceration with necrosis and stomatitis, worsening over the past 24 hours and associated with reduced oral intake and incomplete opening of the mouth. Presentation was accompanied by a generalized rash and genital mucosal involvement. The only new systemically ingested agent was dimenhydrinate approximately 4 days prior to admission. She had no significant medical history, but was labeled to be allergic to acetaminophen. She had a positive history of 2 similar presentations secondary to Panadol Menstrual (acetaminophen and pamabrom), once 3 years ago and again 5 months prior to the current admission. An objective causality assessment revealed that the adverse drug event was “probable” to dimenhydrinate. A detailed history revealed a negative drug challenge to acetaminophen. She had previously taken plain acetaminophen and Beserol (acetaminophen and chlormezanone) with no reaction. Discussion: A comprehensive history taking facilitated the diagnosis of erythema multiforme secondary to dimenhydrinate without the need to perform invasive testing, and the removal of erroneous allergy labeling to acetaminophen. Dimenhydrinate and pamabron both contain theophylline-related structures in their chemical composition. Similar reactions to pamabrom strongly suggested cross-sensitivity to theophylline-related structures. Conclusions: To our knowledge, this is the first report of erythema multiforme due to dimenhydrinate with pamabron cross-sensitivity. We recommend that comprehensive medication-history taking be carried out for all drug-allergy patients to ensure greater informed decision making when choosing medications to use for that patient in the future.

A B S T R A C T Objective: The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors. Study design: This is a case–control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test. Results: Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p < 0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p < 0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p < 0.0089). Poor outcomes were associated with early start of symptoms (p < 0.019), and treatment with methylprednisolone (p < 0.0217), promethazine (p < 0.0386), and other antihistamines [diphenhydramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p < 0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome. Conclusion: Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy.

OBJECTIVE: Vomiting is a common symptom in children with infectious gastroenteritis. It contributes to fluid loss and is a limiting factor for oral rehydration therapy. Dimenhydrinate has traditionally been used for children with gastroenteritis in countries such as Canada and Germany. We investigated the efficacy and safety of dimenhydrinate in children with acute gastroenteritis. METHODS: We performed a prospective, randomized, placebo-controlled, multicenter trial. We randomly assigned 243 children with presumed gastroenteritis and vomiting to rectal dimenhydrinate or placebo. Children with no or mild dehydration were included. All children received oral rehydration therapy. Primary outcome was defined as weight gain within 18 to 24 hours after randomization. Secondary outcomes were number of vomiting episodes, fluid intake, parents' assessment of well-being, number of diarrheal episodes, and admission rate to hospital. We recorded potential adverse effects. RESULTS: Change of weight did not differ between children who received dimenhydrinate or placebo. The mean number of vomiting episodes between randomization and follow-up visit was 0.64 in the dimenhydrinate group and 1.36 in the placebo group. In total, 69.6% of the children in the dimenhydrinate group versus 47.4% in the placebo group were free of vomiting between randomization and the follow-up visit. Hospital admission rate, fluid intake, general well-being of the children, and potential adverse effects, including the number of diarrhea episodes, were similar in both groups. CONCLUSIONS: Dimenhydrinate reduces the frequency of vomiting in children with mild dehydration; however, the overall benefit is low, because it does not improve oral rehydration and clinical outcome.

Meniere's disease (MD) is a disorder of the inner ear that causes vertigo attacks, fluctuating hearing loss, tinnitus and aural fullness. The aetiology of MD is multifactorial. A characteristic sign of MD is endolymphatic hydrops (EH), a disorder in which excessive endolymph accumulates in the inner ear and causes damage to the ganglion cells. In most patients, the clinical symptoms of MD present after considerable accumulation of endolymph has occurred. However, some patients develop symptoms in the early stages of EH. The reason for the variability in the symptomatology is unknown and the relationship between EH and the clinical symptoms of MD requires further study. The diagnosis of MD is based on clinical symptoms but can be complemented with functional inner ear tests, including audiometry, vestibular-evoked myogenic potential testing, caloric testing, electrocochleography or head impulse tests. MRI has been optimized to directly visualize EH in the cochlea, vestibule and semicircular canals, and its use is shifting from the research setting to the clinic. The management of MD is mainly aimed at the relief of acute attacks of vertigo and the prevention of recurrent attacks. Therapeutic options are based on empirical evidence and include the management of risk factors and a conservative approach as the first line of treatment. When medical treatment is unable to suppress vertigo attacks, intratympanic gentamicin therapy or endolymphatic sac decompression surgery is usually considered. This Primer covers the pathophysiology, symptomatology, diagnosis, management, quality of life and prevention of MD.

Summary In this study, we aimed to investigate and compare the direct toxic and teratogenic effects of dimenhydrinate, metoclopramide and trimethobenzamide HCl, antiemetic drugs on embryonic growth and development in cultured rat embryos. Embryos were explanted on day 9.5 of gestation and cultured. Whole rat serum was used as a culture medium for the control group while different concentrations of dimenhydrinate (2.5–20 μg/ml), metoclopramide (10–50 μg/ml) and trimethobenzamide HCl (25–100 μg/ml) were added to serum for the experimental groups. Effects of antiemetics on embryonic developmental parameters were compared, and embryos were evaluated for the presence of any malformations. Also, the total DNA was extracted from the cells to determine the fragmentation of nuclear DNA of embryonic cells. Compared with the control embryos, the antiemetics significantly decreased all growth and developmental parameters dose dependently. There was no difference regarding the fragmentation of nuclear DNA of the all used agents and controls. Amongst the agents, trimethobenzamide HCl was found to have more toxic and teratogenic potential, and metoclopramide appears to be the least toxic antiemetic and therefore could be more safely used and might be preferred for the treatment of nausea and vomiting in pregnancy.

Background: Vestibular neuritis (VN) is a strongly disabling disease of the peripheral vestibular system. Rapid and effective relief of symptoms is important to allow patients to promptly return to normal physical activity. Objective: The aim of this prospective, randomized, double-blind study was to evaluate the efficacy of a fixed low-dose combination of cinnarizine and dimenhydrinate in unilateral VN in comparison with betahistine in terms of improvement of vertigo and concomitant symptoms, and performance in neurotological testing. Methods: Sixty-two patients were randomized to receive either cinnarizine 20 mg/dimenhydrinate 40 mg as a fixed combination or betahistine 12mg, each three times daily for 4 weeks. Vertigo and concomitant symptoms, activities of daily living (ADL), posturography and a battery of vestibulo-ocular tests, registered by electronystagmography including spontaneous nystagmus, bithermal caloric and rotatory test, among others, were assessed at baseline (t0), after 1 week (t1w) and after 4 weeks (t4w). The primary endpoint was the Mean Vertigo Score (MVS) at t1w, a composite of 12 individual scores for unprovoked and provoked vertigo, each assessed using a 10 cm visual analogue scale (VAS). Non-inferiority of the fixed combination versus betahistine would be assumed if the two-sided 95% confidence intervals (CIs) for between-group differences in MVS lay entirely below the non-inferiority margin of 1.25 (12.5% of VAS range). Results: The fixed combination led to significantly greater improvements in MVS than betahistine both at t1w (primary endpoint) and at t4w (95% CI for the difference in baseline-adjusted means −0.95, −0.64 at t1w, −0.77, −0.44 at t4w; p < 0.001). Vegetative symptoms and ADL also improved significantly more under the fixed combination than under betahistine at t1w (p< 0.001, each parameter) and t4w (p

OBJECTIVE: To evaluate the efficacy and safety of oral dimenhydrinate in the treatment of acute gastroenteritis. METHODS: This was a randomized, double-blind, placebo-controlled trial conducted in the emergency department of a pediatric university-affiliated center. Children 1 to 12 years old who presented to the emergency department with at least 5 episodes of vomiting in the previous 12 hours and diagnosed with acute gastroenteritis were block-randomized to receive oral dimenhydrinate (1 mg/kg; maximum: 50 mg) every 6 hours for 4 doses or placebo for 4 doses. The primary outcome measure was treatment failure as defined by the occurrence of ≥2 episodes of vomiting in the 24 hours after administration of the first dose of the study medication. RESULTS: During the study period, 209 patients met inclusion criteria, but 50 refused to participate and 7 were missed. Eight participants were lost to follow-up, and 144 were thus included in the primary analysis. Of these patients, 74 were randomized to receive dimenhydrinate and 70 placebo. The proportions of patients showing failure of treatment were similar for both treatment groups: dimenhydrinate, 31% (23 of 74); placebo, 29% (20 of 70) (difference: 0.02 [95% confidence interval: –0.12 to 0.17]). There were no differences between the 2 groups in rates of intravenous cathether insertion, mean number of episodes of vomiting or diarrhea, abdominal pain, nausea, duration of symptoms, revisit rates, or parental absenteeism. The proportions of adverse effects were similar in both groups (53% vs 54%). CONCLUSIONS: The prescription of oral dimenhydrinate did not significantly decrease the frequency of vomiting in children with acute gastroenteritis compared with placebo.