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Toxicology Reports 2020has been traditionally used as an antiemetic. Additionally, it has been used in various herbal formulations for the treatment of emesis. So far, there is no scientific...
has been traditionally used as an antiemetic. Additionally, it has been used in various herbal formulations for the treatment of emesis. So far, there is no scientific evidence of the plant extract as antiemetic. Therefore, this study was intended to assess the antiemetic activity of Juice (JCR), aqueous (CRAE) and methanolic extract (CRME) of in pigeons. Emesis was induced through GIT irritants like ampicillin (300 mg/kg, IM), copper sulphate (100 mg/kg, PO), conc. sodium chloride solution (1600 mg/kg, PO) and cisplatin (5-HT receptor stimulator) (6 mg/kg, IM). Dimenhydrinate acted as a positive control (2 mg/kg; IM). JCR [(1 ml/kg (1 %) and 1 ml/kg (2 %)], CRAE, and CRME were administered intramuscularly at different doses (50, 100 and 200 mg/kg) to each pigeon ( = 6). In each group, calculation of total number of jerks & vomiting episodes, and vomiting-weight was carried out to evaluate its antiemetic activity. The JCR exhibited a significant ( < 0.05) antiemetic impact on both the frequency and onset of emesis at 1 ml/kg (2 %) against various emesis mediator, except sodium chloride. Similarly, CRAE and CRME elicited marked dose dependent inhibition both on onset and frequency of emesis with highly significant ( < 0.001) effect at 200 mg/kg. The study reflects that juice, aqueous and methanolic extract of have significant antiemetic potential and possess pharmacological active constituent(s) that interfered with the emetic mediators by acting through GIT irritation and 5-HT receptor stimulations. Results of this study provide a scientific background to its traditional antiemetic uses.
PubMed: 33024704
DOI: 10.1016/j.toxrep.2020.09.009 -
Turkish Archives of Otorhinolaryngology Dec 2019Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular system disease causing dizziness. It occurs more in the 5th decade of life and...
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 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<0.001). No statistically significant differences were found in terms of DHI scores between Group 1 (repositioning maneuver only) and Group 2 (repositioning maneuver plus betahistine or dimenhydrinate).
CONCLUSION
The most effective treatment method of BPPV is repositioning maneuver. Addition of betahistine or dimenhydrinate pharmacotherapy to repositioning maneuver did not show superiority to treatment with repositioning maneuvers alone.
PubMed: 32128517
DOI: 10.5152/tao.2019.4185 -
CMAJ : Canadian Medical Association... Feb 2020
Topics: Aged; Antiemetics; Benign Paroxysmal Positional Vertigo; Dimenhydrinate; Head Impulse Test; Hearing Tests; Humans; Male; Middle Aged; Neurologic Examination; Nystagmus, Pathologic; Patient Positioning; Vestibular Neuronitis
PubMed: 32094268
DOI: 10.1503/cmaj.190334 -
International Journal of Environmental... Feb 2020Medication 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...
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. 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. The prevalence of medication use was 92.5% (95% CI 91.7-93.3), excluding iron salts, folic acid, vitamins, and other minerals. The prevalence of self-medication was 27.7% (95% CI 26.3-29.1). 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. 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.
Topics: Acetaminophen; Adult; Brazil; Cohort Studies; Dietary Supplements; Female; Folic Acid; Humans; Interviews as Topic; Pharmacoepidemiology; Pregnancy; Prenatal Care; Prevalence; Qualitative Research; Self Medication; Surveys and Questionnaires; Vitamins; Young Adult
PubMed: 32033282
DOI: 10.3390/ijerph17030989 -
Cancer Medicine Mar 2020Previous studies have shown that forkhead box P4 antisense RNA 1 (FOXP4-AS1) is dysregulated in tumor tissues and can serve as a prognostic indicator for multiple...
Previous studies have shown that forkhead box P4 antisense RNA 1 (FOXP4-AS1) is dysregulated in tumor tissues and can serve as a prognostic indicator for multiple cancers. However, the clinical significance of FOXP4-AS1 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The goal of this study is to recognize the possible clinical significance of long noncoding RNA FOXP4-AS1 in patients with early stage PDAC. A total of 112 patients from The Cancer Genome Atlas (TCGA) PDAC cohort, receiving RNA sequencing, were involved in the study. Survival analysis, functional mechanism, and potential small molecule drugs of target therapy of FOXP4-AS1 were performed in this study. Survival analysis in TCGA PDAC cohort suggested that patients with high FOXP4-AS1 expression had significantly augmented possibility of death than in PDAC patients with lower FOXP4-AS1 expression (adjusted P = .008; adjusted HR = 2.143, 95% CI = 1.221-3.760). In this study, a genome-wide RNA sequencing dataset was used to identify 927 genes co-expressing with FOXP4-AS1 in PDAC tumor tissues. A total of 676 differentially expressed genes were identified between different FOXP4-AS1 expression groups. Functional enrichment analysis of these genes and gene set enrichment analysis for PDAC genome-wide RNA sequencing dataset was done. We have found that FOXP4-AS1 may function in PDAC by participating in biological processes and pathways including oxidative phosphorylation, tricarboxylic acid cycle, classical tumor-related pathways such as NF-kappaB as well as Janus kinase/signal transducers in addition to activators of transcription, cell proliferation, and adhesion. In addition, we also screened two potential targeted therapeutic small molecule drugs (dimenhydrinate and metanephrine) for FOXP4-AS1 in PDAC. In conclusion, our present study demonstrated that higher expression of FOXP4-AS1 in PDAC tumor tissues were related with an inferior medical outcome. Through multiple genome-wide approaches, we identified the potential molecular mechanisms of FOXP4-AS1 in PDAC and two targeted therapeutic drugs for it.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Cell Proliferation; Citric Acid Cycle; Cohort Studies; Datasets as Topic; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Neoplasm Staging; Nomograms; Oxidative Phosphorylation; Pancreas; Pancreatic Neoplasms; Pancreaticoduodenectomy; RNA, Long Noncoding; RNA-Seq; Survival Analysis
PubMed: 31991068
DOI: 10.1002/cam4.2818 -
Indian Journal of Otolaryngology and... Nov 2019Cinnarizine, is approved for nausea, vomiting, motion sickness, inner ear disorders and is considered as first-line pharmacotherapy for management of vertigo. It acts by...
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.
PubMed: 31750127
DOI: 10.1007/s12070-017-1120-7 -
BMC Cancer Nov 2019Chemotherapy-induced nausea and vomiting (CINV) belong among the most burdensome side effects in hemato-oncology. Mostly, a combination of ondansetron and dexamethasone... (Observational Study)
Observational Study
Efficacy, safety and feasibility of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric patients receiving moderately and highly emetogenic chemotherapy - results of a non-interventional observation study.
BACKGROUND
Chemotherapy-induced nausea and vomiting (CINV) belong among the most burdensome side effects in hemato-oncology. Mostly, a combination of ondansetron and dexamethasone is used as antiemetic prophylaxis in pediatric patients undergoing emetogenic chemotherapy. However, dexamethasone is prohibited in different pediatric chemotherapy protocols. Currently, data on the use of ondansetron with the new antiemetic agent fosaprepitant without dexamethasone is not available for pediatric patients.
METHODS
In this non-interventional observation study, 79 pediatric patients with a median age of 8.0 years (range 0.5-17.9 years) who received a CINV prophylaxis regimen with either fosaprepitant (4 mg/kg; maximum 150 mg) and ondansetron (as 24-h continuous infusion) (n = 40; fosaprepitant group/FG) or ondansetron only (n = 39; control group/CG) during moderately or highly emetogenic chemotherapy were analyzed. The groups were analyzed and compared for frequency of vomiting, administered doses of on-demand antiemetic dimenhydrinate and adverse events during the acute (0-24 h after chemotherapy administration) and delayed (> 24 h-120 h) CINV phases.
RESULTS
A total of 112 and 116 chemotherapy blocks were analyzed in the fosaprepitant and the control group, respectively. The emetogenic potential of the administered chemotherapy did not significantly differ (p = 0.8812) between the two cohorts. In the acute CINV phase, the percentage of patients experiencing vomiting (n = 26 patients) and the vomiting events were significantly higher (p = 0.0005 and p < 0.0001, respectively) in the CG (n = 26 patients (66.7%); 88 events) compared with the FG (n = 10 patients (25.0%); 37 events). In the delayed CINV phase, the percentage of patients experiencing vomiting and the vomiting events were also significantly higher (p = 0.0017 and p < 0.0001, respectively) in the CG (n = 31 patients (79.5%); 164 events) compared with the FG (n = 17 patients (42.5%); 103 events). Additionally, significantly more dimenhydrinate doses were administered in the CG compared with the FG patients (n = 322/n = 198; p < 0.0001). The occurrence of adverse events did not significantly differ between the two groups (p > 0.05).
CONCLUSION
Fosaprepitant (4.0 mg/kg) in addition to ondansetron, without application of dexamethasone, was well tolerated, safe, effective and superior to ondansetron only as CINV prophylaxis in pediatric patients during moderately and highly emetogenic chemotherapy.
Topics: Adolescent; Antiemetics; Antineoplastic Agents; Case-Control Studies; Child; Child, Preschool; Feasibility Studies; Female; Humans; Infant; Male; Morpholines; Nausea; Neoplasms; Ondansetron; Patient Safety; Treatment Outcome; Vomiting
PubMed: 31730451
DOI: 10.1186/s12885-019-6252-6 -
Drug Design, Development and Therapy 2019Chemotherapy-induced nausea and vomiting (CINV) are a major burden for patients undergoing emetogenic chemotherapy. International guidelines recommend an antiemetic... (Observational Study)
Observational Study
BACKGROUND
Chemotherapy-induced nausea and vomiting (CINV) are a major burden for patients undergoing emetogenic chemotherapy. International guidelines recommend an antiemetic prophylaxis with corticosteroids, 5-HTR-antagonists and NKR-antagonists. The NKR-antagonist fosaprepitant has shown favorable results in pediatric and adult patients. There is little pediatric experience with fosaprepitant.
METHODS
This non-interventional observation study analyzed 303 chemotherapy courses administered to 83 pediatric patients with a median age of 9 years (2-17 years), who received antiemetic prophylaxis either with fosaprepitant and granisetron with or without dexamethasone (fosaprepitant group/FG; n=41), or granisetron with or without dexamethasone (control group/CG; n=42), during moderately (CINV risk 30-90%) or highly (CINV risk>90%) emetogenic chemotherapy. The two groups' results were compared with respect to the safety and efficacy of the antiemetic prophylaxis during the acute (0-24hrs after chemotherapy), delayed (>24-120hrs after chemotherapy) and both CINV phases. Laboratory and clinical adverse events were compared between the two cohorts.
RESULTS
Adverse events were not significantly different in the two groups (p>0.05). Significantly fewer vomiting events occurred during antiemetic prophylaxis with fosaprepitant in the acute (23 vs 142 events; p<0.0001) and the delayed (71 vs 255 events; p<0.0001) CINV phase. In the control group, the percentage of chemotherapy courses with vomiting was significantly higher during the acute (24%/FG vs 45%/CG; p<0.0001) and delayed CINV phase (28%/FG vs 47%/CG; p=0.0004). Dimenhydrinate (rescue medication) was administered significantly more often in the CG, compared to the FG (114/FG vs 320/CG doses; p<0.0001). Likewise, in the control group, dimenhydrinate was administered in significantly more (p<0.0001) chemotherapy courses during the acute and delayed CINV phases (79 of 150; 52.7%), compared to the fosaprepitant group (45 of 153; 29.4%).
CONCLUSION
Antiemetic prophylaxis with fosaprepitant and granisetron with or without dexamethasone was well tolerated, safe and effective in pediatric patients. However, larger prospective trials are needed to evaluate these findings.
Topics: Adolescent; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cohort Studies; Dexamethasone; Drug Therapy, Combination; Female; Granisetron; Humans; Male; Morpholines; Nausea; Vomiting
PubMed: 31686784
DOI: 10.2147/DDDT.S214264 -
Clinical Drug Investigation Nov 2019Vertigo derived from peripheral vestibular disorders is quite frequently encountered in daily clinical practice and can be a severely disabling symptom associated with... (Comparative Study)
Comparative Study Randomized Controlled Trial
Efficacy and Safety of a Fixed Combination of Cinnarizine 20 mg and Dimenhydrinate 40 mg vs Betahistine Dihydrochloride 16 mg in Patients with Peripheral Vestibular Vertigo: A Prospective, Multinational, Multicenter, Double-Blind, Randomized, Non-inferiority Clinical Trial.
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.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Betahistine; Cinnarizine; Dimenhydrinate; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Prospective Studies; Vertigo; Young Adult
PubMed: 31571128
DOI: 10.1007/s40261-019-00858-6