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Plants (Basel, Switzerland) Dec 2023Quercetin (QUA), a flavonoid compound, is ubiquitously found in plants and has demonstrated a diverse range of biological activities. The primary objective of the...
Quercetin (QUA), a flavonoid compound, is ubiquitously found in plants and has demonstrated a diverse range of biological activities. The primary objective of the current study is to assess the potential antiemetic properties of QUA using an in vivo and in silico approach. In this experiment, 4-day-old chicks were purchased to induce emesis by orally administering copper sulfate pentahydrate (CuSO·5HO) at a dose of 50 mg/kg (orally). Domperidone (DOM) (6 mg/kg), Hyoscine (HYS) (21 mg/kg), and Ondansetron (OND) (5 mg/kg) were treated as positive controls (PCs), and distilled water and a trace amount of Tween 80 mixture was employed as a negative control (NC). QUA was given orally at two distinct doses (25 and 50 mg/kg). Additionally, QUA (50 mg/kg) and PCs were administered separately or in combination to assess their antagonistic or synergistic effects on the chicks. The binding affinity of QUA and referral ligands towards the serotonin receptor (5HT3), dopamine receptors (D2 and D3), and muscarinic acetylcholine receptors (M1-M5) were estimated, and ligand-receptor interactions were visualized through various computational tools. In vivo findings indicate that QUA (25 and 50 mg/kg) has a significant effect on reducing the number of retches (16.50 ± 4.65 and 10.00 ± 4.19 times) and increasing the chick latency period (59.25 ± 4.75 and 94.25 ± 4.01 s), respectively. Additionally, QUA (50 mg/kg) in combination with Domperidone and Ondansetron exhibited superior antiemetic effects, reducing the number of retches and increasing the onset of emesis-inducing time. Furthermore, it is worth noting that QUA exhibited the strongest binding affinity against the D2 receptor with a value of -9.7 kcal/mol through the formation of hydrogen and hydrophobic bonds. In summary, the study found that QUA exhibited antiemetic activity in chicks, potentially by interacting with the D2 receptor pathway.
PubMed: 38140516
DOI: 10.3390/plants12244189 -
International Breastfeeding Journal Apr 2024A lack of safety data on postpartum medication use presents a potential barrier to breastfeeding and may result in infant exposure to medications in breastmilk. The type...
BACKGROUND
A lack of safety data on postpartum medication use presents a potential barrier to breastfeeding and may result in infant exposure to medications in breastmilk. The type and extent of medication use by lactating women requires investigation.
METHODS
Data were collected from the CHILD Cohort Study which enrolled pregnant women across Canada between 2008 and 2012. Participants completed questionnaires regarding medications and non-prescription medications used and breastfeeding status at 3, 6 and 12 months postpartum. Medications, along with self-reported reasons for medication use, were categorized by ontologies [hierarchical controlled vocabulary] as part of a large-scale curation effort to enable more robust investigations of reasons for medication use.
RESULTS
A total of 3542 mother-infant dyads were recruited to the CHILD study. Breastfeeding rates were 87.4%, 75.3%, 45.5% at 3, 6 and 12 months respectively. About 40% of women who were breastfeeding at 3 months used at least one prescription medication during the first three months postpartum; this proportion decreased over time to 29.5% % at 6 months and 32.8% at 12 months. The most commonly used prescription medication by breastfeeding women was domperidone at 3 months (9.0%, n = 229/2540) and 6 months (5.6%, n = 109/1948), and norethisterone at 12 months (4.1%, n = 48/1180). The vast majority of domperidone use by breastfeeding women (97.3%) was for lactation purposes which is off-label (signifying unapproved use of an approved medication). Non-prescription medications were more often used among breastfeeding than non-breastfeeding women (67.6% versus 48.9% at 3 months, p < 0.0001), The most commonly used non-prescription medications were multivitamins and Vitamin D at 3, 6 and 12 months postpartum.
CONCLUSIONS
In Canada, medication use is common postpartum; 40% of breastfeeding women use prescription medications in the first 3 months postpartum. A diverse range of medications were used, with many women taking more than one prescription and non-prescription medicines. The most commonly used prescription medication by breastfeeding women were domperidone for off-label lactation support, signalling a need for more data on the efficacy of domperidone for this indication. This data should inform research priorities and communication strategies developed to optimize care during lactation.
Topics: Infant; Female; Humans; Pregnancy; Breast Feeding; Lactation; Domperidone; Cohort Studies; Prospective Studies; Canada; Prescriptions
PubMed: 38589955
DOI: 10.1186/s13006-024-00628-x -
Veterinary Sciences Jan 2024Domperidone is used as an immunomodulatory drug for infection and disease in dogs. However, a pro-arrhythmic side effect, caused by prolonged QT intervals, is reported...
Domperidone is used as an immunomodulatory drug for infection and disease in dogs. However, a pro-arrhythmic side effect, caused by prolonged QT intervals, is reported in humans. This pilot study evaluated the corrected QT (QTc) interval in dogs treated with domperidone for preventive or therapeutic management of leishmaniosis. The electrocardiogram and blood concentration of creatinine, urea nitrogen, sodium, potassium, and chloride were evaluated seven days before the start and on the last day of therapy in 17 dogs receiving domperidone for four weeks. In two dogs, the QTc interval was measured before and 2 h, 3 h, and 12 h after administration of the drug on the first day of treatment. After treatment, QTc measures and chloride concentrations increased significantly, although the QTc value slightly exceeded the upper reference limit only in one dog, and chloride concentrations were always normal. Creatinine concentrations significantly decreased after therapy. In the two dogs monitored at different times on the first day of treatment, QTc values were always normal. Domperidone caused a slight prolongation of QTc interval, and further studies should be made for a risk assessment in dogs with cardiac diseases, electrolytic imbalance, and in those receiving drugs increasing QT interval or competing with domperidone metabolism.
PubMed: 38250945
DOI: 10.3390/vetsci11010039 -
Cureus May 2024Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like...
Prevalence, Attributes, and Risk Factors of QT-Interval-Prolonging Drugs and Potential Drug-Drug Interactions in Cancer Patients: A Prospective Study in a Tertiary Care Hospital.
Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like antiemetics, antidepressants, analgesics, and antimicrobials), there is a heightened risk for possible QT interval prolongation. There is a dearth of evidence in the literature regarding the usage of QT-prolonging anticancer drugs and associated risk factors that have the propensity to prolong QT interval. The purpose was to explore the extent of the use of QT-interval-prolonging drugs and potential QT-prolonging drug-drug interactions (QT-DDIs) in cancer patients attending OPD in a tertiary-care hospital. Methods This was a hospital-based, cross-sectional, observational study. Risk stratification of QT-prolonging drugs for torsades de pointes (TdP) was done by the Arizona Center for Education and Research on Therapeutics (AzCERT)/CredibleMeds-lists, and potential QT-DDIs were determined with four online DDI-checker-software. Results In 1331 cancer patients, the overall prevalence of potential QT-prolonging drug utilization was 97.3%. Ondansetron, pantoprazole, domperidone, and olanzapine were the most frequent QT-prolonging drugs in cancer patients. The top six antineoplastics with potential QT-prolonging and torsadogenic actions were capecitabine, oxaliplatin, imatinib, bortezomib, 5-fluorouracil, and bendamustine. Evidence-based pragmatic QTc interval prolongation risk assessment tools are imperative for cancer patients. Conclusion This study revealed a high prevalence of QT-prolonging drugs and QT-DDIs among cancer patients who are treated with anticancer and non-anticancer drugs. As a result, it's critical to take precautions, stay vigilant, and avoid QT-prolonging in clinical situations. Evidence-based pragmatic QTc interval prolongation risk assessment tools are needed for cancer patients.
PubMed: 38882995
DOI: 10.7759/cureus.60492 -
Saudi Pharmaceutical Journal : SPJ :... May 2024Metoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and...
BACKGROUND
Metoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and associated side effects of prolonged-use metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis (SSc).
METHODS
A quantitative observational survey was conducted by interview questionnaire in rheumatology outpatients at a tertiary teaching hospital in Riyadh, Saudi Arabia. The study included all patients aged 25-80 years diagnosed with SSc. All patients were on metoclopramide or domperidone for the treatment of chronic gastrointestinal dysmotility symptoms over at least 12 weeks.
RESULTS
Eighteen eligible patients were included. Most study participants were diagnosed with SSc complicated by interstitial lung disease (n = 13; 72.2 %). The most frequently reported side effect that occurred while taking prokinetic drugs was shortness of breath (n = 12; 66.7 %). None of the participants reported experiencing depression, galactorrhea, or syncope. CNS side effects were reported in 5.6 %. There were no differences in side effects based on the type and dosage of prokinetic drug used.
CONCLUSIONS
Use of metoclopramide and domperidone for the treatment of chronic gastrointestinal dysmotility in SSc patients for 12 weeks or longer was not associated with any troublesome side effects. Further studies with more participants are needed to confirm our findings.
PubMed: 38558884
DOI: 10.1016/j.jsps.2024.102039 -
International Journal of Medical... 2023Herbal galactagogues have been widely used as a treatment for postpartum hypogalactia due to the potential side effects associated with pharmacological therapy....
Herbal galactagogues have been widely used as a treatment for postpartum hypogalactia due to the potential side effects associated with pharmacological therapy. Tri-Than-Thip (Tri-TT) is a Thai herbal medicine remedy that contains three main components: . These components are believed to have properties that contribute to milk production. However, despite the traditional use of Tri-TT, there is a lack of academic evidence supporting its efficacy in enhancing milk production. Therefore, the purpose of this study was to investigate the effect of Tri-TT on milk production and determine if it has a galactagogue effect. The weight suckle weight model was used to determine total milk production in lactating rats, while histological analysis was performed to assess the alveolar diameter of the mammary gland. The findings of this study revealed a significant increase in total milk production among lactating rats treated with 500 mg/kg of Tri-TT, compared to the control group. Furthermore, both the Tri-TT and Domperidone-treated groups exhibited a larger alveolar diameter of the mammary gland in comparison to the control group. In summary, these findings provide supportive evidence for the galactagogue activity of Tri-TT. The observed enhancement in milk production may be associated with Tri-TT could potentially be attributed to its ability to widen the alveolar diameter of the mammary gland, thereby facilitating increased milk volume.
Topics: Female; Rats; Animals; Milk; Lactation; Galactogogues
PubMed: 37575273
DOI: 10.7150/ijms.83869 -
Heliyon Apr 2024Food accumulation fever (FAF), a common clinical disease in children, is generally induced by the excessive intake of high-calorie or high-fat foods. decoction (ZQCLD)...
OBJECTIVE
Food accumulation fever (FAF), a common clinical disease in children, is generally induced by the excessive intake of high-calorie or high-fat foods. decoction (ZQCLD) is a classical traditional Chinese medicine (TCM) that may have therapeutic effects on FAF.
METHODS
Network pharmacological analyses of ZQCLD and FAF were conducted. Animal experiments lasted for 14 days. Rats in the model, positive control, and low-, medium-, and high-dose groups were fed a high-calorie diet. On days 11-14, the positive group was given a domperidone solution. The low-, medium-, and high-dose groups were administered different concentrations of ZQCLD. The body temperature, gastric emptying rate, and intestinal propulsion rate were measured. Relevant indicators were determined by ELISA.
RESULTS
The main target proteins included IL-1β, C-C motif chemokine 2 (CCL2), prostaglandin G/H synthase 2 (PTGS2), transcription factor AP-1 (JUN), haem oxygenase 1 (HMOX1), interferon-gamma (IFN-γ), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and inducible nitric oxide synthase (NOS2/iNOS). Compared with those in the control group, body weight, gastric emptying rate, intestinal propulsion rate, and neuronal nitric oxide synthase (NOS1/nNOS) levels were significantly lower in the model group, whereas body temperature and endotoxin, interleukin-1β (IL-1β), PGE2, and iNOS levels were increased. In each treatment group, body temperature and PGE2 levels returned to normal levels. Compared with those in the model group, the gastric emptying rates in the positive group and the low- and medium-dose groups increased; the intestinal propulsion rates were higher in the medium- and high-dose groups, whereas the endotoxin and IL-1β levels were lower; and the nNOS level was higher in the high-dose group, whereas the iNOS level was lower.
CONCLUSIONS
ZQCLD may treat FAF by regulating jejunal IL-1β and nNOS, serum endotoxin, and hypothalamic PGE2 and iNOS levels.
PubMed: 38681542
DOI: 10.1016/j.heliyon.2024.e29813 -
The Indian Journal of Medical Research Feb 2024Irrational prescribing practices have major consequences on patient safety and also increase the economic burden. Real-life examples of impact of irrational prescription... (Observational Study)
Observational Study
BACKGROUND OBJECTIVES
Irrational prescribing practices have major consequences on patient safety and also increase the economic burden. Real-life examples of impact of irrational prescription have potential to improve prescribing practices. In this context, the present study aimed to capture and evaluate the prevalence of deviations from treatment guidelines in the prescriptions, potential consequence/s of the deviations and corrective actions recommended by clinicians.
METHODS
It was a cross-sectional observational study conducted in the outpatient departments of tertiary care hospitals in India wherein the 13 Indian Council of Medical Research Rational Use of Medicines Centres are located. Prescriptions not compliant with the standard treatment guidelines and incomplete prescriptions with respect to formulation, dose, duration and frequency were labelled as 'prescriptions having deviations'. A deviation that could result in a drug interaction, lack of response, increased cost, preventable adverse drug reaction (ADR) and/or antimicrobial resistance was labelled as an 'unacceptable deviation'.
RESULTS
Against all the prescriptions assessed, about one tenth of them (475/4838; 9.8%) had unacceptable deviations. However, in 2667/4838 (55.1%) prescriptions, the clinicians had adhered to the treatment guidelines. Two thousand one hundred and seventy-one prescriptions had deviations, of which 475 (21.9%) had unacceptable deviations with pantoprazole (n=54), rabeprazole+domperidone (n=35) and oral enzyme preparations (n=24) as the most frequently prescribed drugs and upper respiratory tract infection (URTI) and hypertension as most common diseases with unacceptable deviations. The potential consequences of deviations were increase in cost (n=301), ADRs (n=254), drug interactions (n=81), lack of therapeutic response (n=77) and antimicrobial resistance (n=72). Major corrective actions proposed for consideration were issuance of an administrative order (n=196) and conducting online training programme (n=108).
INTERPRETATION CONCLUSIONS
The overall prevalence of deviations found was 45 per cent of which unacceptable deviations was estimated to be 9.8 per cent. To minimize the deviations, clinicians recommended online training on rational prescribing and administrative directives as potential interventions.
Topics: Humans; Cross-Sectional Studies; Tertiary Care Centers; Prescriptions; Drug-Related Side Effects and Adverse Reactions; India; Anti-Bacterial Agents; Drug Prescriptions
PubMed: 38528817
DOI: 10.4103/ijmr.ijmr_2309_22 -
International Breastfeeding Journal Mar 2024We present a case of non-puerperal induced lactation in transgender woman. Medical literature on lactation induction for transgender women is scarce, and the majority of...
BACKGROUND
We present a case of non-puerperal induced lactation in transgender woman. Medical literature on lactation induction for transgender women is scarce, and the majority of literature and protocols on lactation induction is based on research in cisgender women. Healthcare professionals may lack the precise knowledge about lactation induction and may therefore feel insecure when advice is requested. Subsequently, there is a rising demand for guidelines and support.
METHODS
Patient medical record was consulted and a semi-structured interview was conducted to explore the motive for lactation induction, the experience of lactation induction, and to gather additional information about the timeline and course of events.
CASE PRESENTATION
In this case a 37-year-old transgender woman, who was under the care of the centre of expertise on gender dysphoria in Amsterdam, and in 2020 started lactation induction because she had the wish to breastfeed her future infant. She was in a relationship with a cisgender woman and had been using gender affirming hormone therapy for 13 years. Prior to initiating gender affirming hormone therapy she had cryopreserved her semen. Her partner conceived through Intracytoplasmic Sperm Injection, using our patient's cryopreserved sperm. To induce lactation, we implemented a hormone-regimen to mimic pregnancy, using estradiol and progesterone, and a galactogogue; domperidone. Our patient started pumping during treatment. Dosage of progesterone and estradiol were significantly decreased approximately one month before childbirth to mimic delivery and pumping was increased. Our patient started lactating and although the production of milk was low, it was sufficient for supplementary feeding and a positive experience for our patient. Two weeks after birth, lactation induction was discontinued due to suckling problems of the infant and low milk production.
CONCLUSIONS
This case report underlined that lactation induction protocols commonly used for cisgender women are also effective in transgender women. However, the amount of milk produced may not be sufficient for exclusive nursing. Nevertheless, success of induced lactation may be attributed to its importance for parent-infant bonding, rather than the possibility of exclusive chestfeeding.
Topics: Adult; Female; Humans; Male; Breast Feeding; Estradiol; Lactation; Progesterone; Semen; Transgender Persons
PubMed: 38462609
DOI: 10.1186/s13006-024-00624-1 -
Scientific Reports Mar 2024The present study was designed to evaluate the antiemetic activity of abietic acid (AA) using in vivo and in silico studies. To assess the effect, doses of 50 mg/kg...
The present study was designed to evaluate the antiemetic activity of abietic acid (AA) using in vivo and in silico studies. To assess the effect, doses of 50 mg/kg b.w. copper sulfate (CuSO⋅5HO) were given orally to 2-day-old chicks. The test compound (AA) was given orally at two doses of 20 and 40 mg/kg b.w. On the other hand, aprepitant (16 mg/kg), domperidone (6 mg/kg), diphenhydramine (10 mg/kg), hyoscine (21 mg/kg), and ondansetron (5 mg/kg) were administered orally as positive controls (PCs). The vehicle was used as a control group. Combination therapies with the referral drugs were also given to three separate groups of animals to see the synergistic and antagonizing activity of the test compound. Molecular docking and visualization of ligand-receptor interaction were performed using different computational tools against various emesis-inducing receptors (D, D, 5HT, H, and M-M). Furthermore, the pharmacokinetics and toxicity properties of the selected ligands were predicted by using the SwissADME and Protox-II online servers. Findings indicated that AA dose-dependently enhances the latency of emetic retching and reduces the number of retching compared to the vehicle group. Among the different treatments, animals treated with AA (40 mg/kg) exhibited the highest latency (98 ± 2.44 s) and reduced the number of retching (11.66 ± 2.52 times) compared to the control groups. Additionally, the molecular docking study indicated that AA exhibits the highest binding affinity (- 10.2 kcal/mol) toward the M receptors and an elevated binding affinity toward the receptors 5HT (- 8.1 kcal/mol), M (- 7.7 kcal/mol), M (- 8.7 kcal/mol), and H (- 8.5 kcal/mol) than the referral ligands. Taken together, our study suggests that AA has potent antiemetic effects by interacting with the 5TH and muscarinic receptor interaction pathways. However, additional extensive pre-clinical and clinical studies are required to evaluate the efficacy and toxicity of AA.
Topics: Animals; Antiemetics; Molecular Docking Simulation; Ondansetron; Vomiting; Receptors, Muscarinic; Abietanes
PubMed: 38503897
DOI: 10.1038/s41598-024-57173-0