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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 -
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 -
Drug Delivery and Translational Research Oct 2019The objective of the study was the development and in vitro characterization of a self-emulsifying drug delivery system (SEDDS) for the nasal application of...
The objective of the study was the development and in vitro characterization of a self-emulsifying drug delivery system (SEDDS) for the nasal application of dimenhydrinate. Final composition of SEDDS was established based on drug solubility and stability studies. Dimenhydrinate was loaded into the SEDDS pre-concentrates to 7.5% (m/v). The droplet size of the final SEDDS formulations was in a range between 60 and 220 nm. Permeability, as well as tissue toxicity, of the formulations was investigated using bovine nasal mucosa. Enhancement in permeation up to 2.8-fold compared to pure dimenhydrinate was confirmed. Furthermore, toxicity studies did not reveal any serious tissue damages related to the SEDDS. Additionally, irritation potential of SEDDS was evaluated in ciliary beat frequency measurements. Incorporation of dimenhydrinate into SEDDS might therefore be considered as a promising approach within the field of nasal delivery of antiemetics by utilizing permeation enhancement strategy.
Topics: Administration, Intranasal; Animals; Antiemetics; Cattle; Cilia; Dimenhydrinate; Drug Delivery Systems; Drug Liberation; Emulsions; In Vitro Techniques; Nasal Mucosa; Permeability; Solubility
PubMed: 30877627
DOI: 10.1007/s13346-019-00634-1 -
BMC Geriatrics Jun 2024Polypharmacy is a global public health concern. This study aimed to determine the prevalence of polypharmacy and trends in the use of commonly used and potentially...
BACKGROUND
Polypharmacy is a global public health concern. This study aimed to determine the prevalence of polypharmacy and trends in the use of commonly used and potentially inappropriate medications among older Korean patients.
METHODS
Individuals aged ≥ 65 years who were prescribed any medication between 2014 and 2018 were selected from the Korean National Health Information Database. Joinpoint regression analyses were used to determine trends in the age-adjusted polypharmacy rates by age group. The prescription rates of the most commonly used medications and the most commonly used potentially inappropriate medications were analysed by year or age group for patients with polypharmacy using the chi-square and proportion difference tests.
RESULTS
This study included 1,849,968 patients, 661,206 (35.7%) of whom had polypharmacy. Age-adjusted polypharmacy rates increased significantly between 2014 and 2018 (P = 0.046). Among patients with polypharmacy, the most commonly prescribed medications were aspirin (100 mg), atorvastatin, metformin, glimepiride, and rosuvastatin. The most commonly prescribed and potentially inappropriate medications were alprazolam, diazepam, amitriptyline, zolpidem, and dimenhydrinate. There was a significant decrease in the prescription rates for each of these drugs in 2018 compared with 2014 among patients with polypharmacy (all P < 0.001), whereas there was a significant increase in alprazolam prescription among patients aged ≥ 85 years when analysed by age group (P < 0.001).
CONCLUSIONS
This study revealed an increasing prevalence of polypharmacy among older adults. Additionally, it highlighted that the utilisation of commonly prescribed potentially inappropriate medications, such as benzodiazepines and tricyclic antidepressants, has remained persistent, particularly among patients aged ≥ 85 years who practiced polypharmacy. These findings provide evidence-based guidance for the development of robust polypharmacy management strategies to ensure medication safety among older adults.
Topics: Humans; Aged; Republic of Korea; Polypharmacy; Male; Female; Potentially Inappropriate Medication List; Aged, 80 and over; Inappropriate Prescribing
PubMed: 38907201
DOI: 10.1186/s12877-024-05141-8 -
Biomolecules & Biomedicine May 2024Dimenhydrinate (DMH), used to alleviate motion sickness symptoms such as nausea, vomiting, dizziness, and vertigo, encounters limitations in oral pharmaceutical...
Dimenhydrinate (DMH), used to alleviate motion sickness symptoms such as nausea, vomiting, dizziness, and vertigo, encounters limitations in oral pharmaceutical formulations due to its poor water solubility and bitter taste. Our research hypothesized that inclusion complexation with β-cyclodextrin (β-CD) might address these drawbacks while ensuring that the newly formed complexes exhibit no cytotoxic or genotoxic effects on peripheral blood mononuclear cells (PBMCs). Inclusion complexes were prepared using the kneading method and the solvent evaporation method. The phase solubility analysis, attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), and differential scanning calorimetry (DSC) were conducted to evaluate the complexation efficacy and stability constant of the new binary systems. The results demonstrated that both methods provided complete and efficient complexation. Cytogenotoxic analysis, including the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, alkaline comet assay, and cytokinesis-block micronucleus cytome (CBMN-cyt) assay, was conducted to assess the cytogenotoxic potential of DMH-β-CD inclusion complexes, a topic previously unexamined. No cytotoxic or genotoxic effects were observed within the concentration range of 36.36 to 109.09 ng/mL. Cell viability of treated PBMCs exceeded 85% for all tested concentrations. No significant increases in DNA strand breaks were observed at any dose, and tail intensity of all complexes remained lower or up to 2.2% higher than the negative control. Parameters indicating genotoxic effects, as well as cytotoxic and cytostatic potential in the CBMN-cyt assay, did not significantly differ from untreated controls. These results suggest that inclusion complexation with β-CD might be a safe and promising solution to overcome the limitations of poor solubility and unpleasant taste of DMH, potentially providing opportunities for new and improved oral pharmaceutical dosage forms.
PubMed: 38819319
DOI: 10.17305/bb.2024.10507 -
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 -
Neurochemical Research Feb 2020Motion sickness (MS) is the visceral discomfort caused due to contradicting visual and vestibular inputs to the brain leading to nausea and vomiting. Sensory conflict...
Motion sickness (MS) is the visceral discomfort caused due to contradicting visual and vestibular inputs to the brain leading to nausea and vomiting. Sensory conflict theory which proves histamine elevations as the primary reason for MS provides a path for an effective pharmaco-therapy. We aimed to evaluate the anti-MS effect of hesperidin (HSP) by modulating histamine and histamine receptor H1 (HRH1) expression. The inhibitory effect of HSP on histamine release was studied in KU812 cells treated with 10 µM calcium ionophore. The in vivo anti-MS effect of HSP was evaluated in Balb/c mice. Thirty six mice were divided into six groups namely, normal control (NC, no rotation), hesperidin at 80 mg/kg body weight control (HSP80, no rotation), motion sickness (MS, rotation induced), dimenhydrinate (Standard drug) at 20 mg/kg body weight + rotation (STD + MS), hesperidin at 40 mg/kg body weight + rotation (HSP40 + MS) and hesperidin at 80 mg/kg body weight + rotation (HSP80 + MS). Hypothalamus and brainstem samples were analysed for histamine levels and HRH1 expression by RT-PCR, Western blot and immunohistochemistry analysis. Calcium ionophore treated KU812 cells significantly increased histamine release when compared to control cells. Pre-treatment with HSP inhibited histamine, HRH1 mRNA and protein expression. Histamine, HRH1 mRNA and protein expression in hypothalamus and brainstem samples of MS group increased significantly when compared to the NC group. Pre-treatment with HSP significantly reduced histamine, HRH1 mRNA and protein expression. Thus, indicating that HSP has a potent anti- MS effect by decreasing the elevated levels of histamine, HRH1 mRNA and protein expression in hypothalamus and brainstem regions.
Topics: Animals; Cell Line, Tumor; Female; Hesperidin; Histamine; Humans; Hypothalamus; Mice, Inbred BALB C; Motion Sickness; RNA, Messenger; Receptors, Histamine H1
PubMed: 31782104
DOI: 10.1007/s11064-019-02923-0 -
International Journal of Clinical... Apr 2020Background Despite growing interest in the negative clinical outcomes of multiple anticholinergic use, limited studies have evaluated anticholinergic burden in the...
Background Despite growing interest in the negative clinical outcomes of multiple anticholinergic use, limited studies have evaluated anticholinergic burden in the geriatric population nationally. Objective To evaluate the prevalence of high anticholinergic burden using the newly developed Korean Anticholinergic Burden Scale in comparison with previous tools and to identify associated factors. Setting National insurance data from a cross section (20%) of older Koreans (2016). Methods Anticholinergic burden was measured using the Korean scale in comparison to the Anticholinergic Drug Scale, Anticholinergic Cognitive Burden, and Anticholinergic Risk Scale. High anticholinergic burden was defined as a summed score of ≥ 3 for concurrent medications or a dose-standardized average daily score of ≥ 3, using each anticholinergic scale. Main outcomes measured Prevalence and predictors of high anticholinergic burden. Results Data of 1,292,323 patients were analyzed. According to the Korean scale, the prevalence of high anticholinergic burden was 25.5%. This result was similar to that from the Anticholinergic Drug Scale (24.9%) and Anticholinergic Cognitive Burden (22.2%). Factors associated with an increased likelihood of anticholinergic burden include: age, gender (female), high Charlson comorbidity index score, polypharmacy, medical aid beneficiary, co-morbidities (such as schizophrenia, depression, urinary incontinence, and Parkinson's disease), frequent healthcare visits, various healthcare facilities utilized, and predominantly visiting hospital-level facilities. According to the Korean Anticholinergic Burden Scale, the major drugs contributing to the anticholinergic burden were ranitidine, chlorpheniramine, tramadol, and dimenhydrinate. Conclusion This study showed that 1 in 4 older Koreans are exposed to high anticholinergic burden. The predictors identified in this research might assist pharmacists in early interventions for their patients.
Topics: Age Factors; Aged; Aged, 80 and over; Cholinergic Antagonists; Comorbidity; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug Utilization; Female; Humans; Insurance Claim Review; Male; Polypharmacy; Republic of Korea; Risk Factors; Sex Factors; Socioeconomic Factors
PubMed: 32281075
DOI: 10.1007/s11096-020-01010-7 -
Clinical Drug Investigation Jan 2020
Topics: Betahistine; Cinnarizine; Dimenhydrinate; Double-Blind Method; Humans; Prospective Studies; Vertigo
PubMed: 31679119
DOI: 10.1007/s40261-019-00872-8 -
BMJ Case Reports Mar 2024Dimenhydrinate is an over-the-counter antihistaminergic medication with anticholinergic properties used to treat nausea or motion sickness worldwide. There is a...
Dimenhydrinate is an over-the-counter antihistaminergic medication with anticholinergic properties used to treat nausea or motion sickness worldwide. There is a well-established correlation between the use of anticholinergic medications and dementia, however, it is unclear if a causal role exists. We report a case of minor neurocognitive disorder in a woman in her 40s with several years of high-dose daily dimenhydrinate abuse who subsequently developed significant delusional beliefs. Her clinical presentation was confounded by numerous other factors that could have impacted her cognition, such as a longstanding presumed learning disability, ankylosing spondylitis with adalimumab treatment, extensive cannabis use or potential development of a primary psychotic disorder. Her workup was within normal limits, and she has not responded to first-line antipsychotic medications to date. This case report adds to the growing evidence supporting concerns about potentially irreversible cognitive deficits in chronic misuse of anticholinergic agents, an association previously observed only in the elderly population.
Topics: Adult; Female; Humans; Middle Aged; Cholinergic Antagonists; Cognitive Dysfunction; Dimenhydrinate; Psychotic Disorders
PubMed: 38453220
DOI: 10.1136/bcr-2023-258493