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BMC Pregnancy and Childbirth Dec 2022Online information about safety of medications during pregnancy and breastfeeding is shown to be conflicting, resulting in anxiety and abstaining from use. The aim of...
Identifying target areas of medicines information efforts to pregnant and breastfeeding women by reviewing questions to SafeMotherMedicine: A Norwegian web-based public medicines information service.
BACKGROUND
Online information about safety of medications during pregnancy and breastfeeding is shown to be conflicting, resulting in anxiety and abstaining from use. The aim of this study was to characterize questions to SafeMotherMedicine, a web-based medicines information service for pregnant and breastfeeding women, to identify target areas that could guide subsequent development of medicines information directed at pregnant and breastfeeding women.
METHODS
The SafeMotherMedicine database contains all questions received through the web-based service and their corresponding answers. A retrospective database analysis of questions received from January 2016 to September 2018 was performed, using descriptive statistics.
RESULTS
A total of 11 618 questions were received including 5 985 questions (51.5%) concerning pregnancy, 4 878 questions (42.0%) concerning breastfeeding, and 755 questions (6.5%) concerning both conditions. The medications in question represented all therapeutic groups with paracetamol (7.0%), ibuprofen (4.1%), cetirizine (3.3%), desloratadine (3.2%) and meclizine (2.8%) being the top five. The 20 medications most frequently asked about for either pregnancy, breastfeeding or both pregnancy and breastfeeding, constituted half of all questions and were used to identify target areas. These included both symptomatic relief of common complaints, such as pain, nausea, and rhinitis, as well as treatment of chronic conditions such as allergy, psychiatric disorders, and asthma. Analysis of a subset of questions showed that most of these questions were asked before use of medications in a current pregnancy (49%) or during breastfeeding (72%). The questions concerned use of medications in all stages of pregnancy and breastfeeding. For 81.6% of the questions concerning pregnancy, and for 84.2% of the questions concerning breastfeeding, information of no or low risk for the foetus or the breastfed infant was provided by SafeMotherMedicine.
CONCLUSIONS
We found that target areas for medicines information directed at pregnant and breastfeeding women included both symptomatic relief of common complaints as well as treatment of chronic conditions. The questions concerned a wide range of medications and involved use in all stages of pregnancy and breastfeeding. Our findings indicate that developing medicines information addressing the identified target areas will meet the information need for a large proportion of this patient group.
Topics: Infant; Pregnancy; Humans; Female; Breast Feeding; Retrospective Studies; Information Services; Hypersensitivity; Internet
PubMed: 36461026
DOI: 10.1186/s12884-022-05252-3 -
BMC Chemistry Sep 2022Pharmaceutical quality control products (QC) demand quick, sensitive, and cost-effective methods to ensure high production at a low cost. Green analytical methods are...
Pharmaceutical quality control products (QC) demand quick, sensitive, and cost-effective methods to ensure high production at a low cost. Green analytical methods are also becoming more common in pharmaceutical research to cut down on the amount of waste that goes into the environment. Meclizine hydrochloride (MZH) and pyridoxine hydrochloride (PYH) are reported to be excellent for calming down COVID-19. As a result, the amount of MZH and PYH manufactured by multinational pharmaceutical organizations has increased considerably during the last several months. The present work proposes three environmentally friendly, straightforward, and sensitive spectrophotometric procedures for quantification of MZH in the presence of PYH in a pure and marketable formulations. The approaches under examination include ratio subtraction (RSM), induced dual wavelength (IDW), and Fourier self-deconvolution (FSD). PYH, on the other hand, was directly quantified at 290 nm. For both drugs, the procedures follow Beer's law in the range of (5-50 µg/mL). The RSM, IDW, and FSD methods, as well as the zero-order approach for PYH, have all been verified in accordance with ICH standards. The ecological value of established methodologies was determined using four distinct ways: the national environmental methods index (NEMI), the analytical Eco-scale, the Analytical Greenness Metric (AGREE), and the green analytical process index (GAPI). Comparing the findings to those of the previously described spectrophotometric technique, no major changes were identified.
PubMed: 36167604
DOI: 10.1186/s13065-022-00860-8 -
In Silico Pharmacology 2022Meclizine is antihistamine and is used in combination with pyridoxine to treat motion sickness. The in-silico study of meclizine prediction studied showed that meclizine...
Meclizine is antihistamine and is used in combination with pyridoxine to treat motion sickness. The in-silico study of meclizine prediction studied showed that meclizine has anti-eczema activity with possible activity 95. This research aimed to explore the anti-eczema activity of meclizine. Therefore, five formulations of meclizine ointment have been prepared using different bases (white base, simple ointment base, hydrophilic petrolatum base, hydrophilic, and emulsifying ointment bases). The efficiency of meclizine ointment has been evaluated by testing the physical compatibility and stability, homogeneity and irritant effect, absorbance and spreadability, chemical identification, calibration curve, drug content (assay), and dissolution test. This is followed by evaluating the ointment's effectiveness on volunteers and molecular docking. Five creams trials have been prepared, and two formulas (F3, and F5) have been selected for further evaluation. The formulas three and five (F3, F5) have passed the physical and chemical tests and showed compatibility, homogenous, absorbed, non-irritant, and stable with calibration curve (R = 0.9999). Then, the F3 formula was selected by testing them on seven volunteers after evaluating the irritant test. Four of the volunteers showed excellent recovery, and three of the volunteers suffered from uncomforting feelings and the formation of new pills. Therefore, F5 has been tested by eight volunteers that contain high oleaginous activity; five showed an excellent recovery, while three of the volunteers showed no difference. According to that, F5 is more efficient for eczema patients than F3, and Meclizine showed promising activity as an anti-eczema that requires further evaluation in the future.
PubMed: 36062215
DOI: 10.1007/s40203-022-00129-x -
Academic Emergency Medicine : Official... May 2023Benign paroxysmal positional vertigo (BPPV) is a very common condition in the population and an important cause of acute vertigo or dizziness in patients presenting to...
Benign paroxysmal positional vertigo (BPPV) is a very common condition in the population and an important cause of acute vertigo or dizziness in patients presenting to an emergency department (ED). Despite this, abundant evidence shows that current ED management of patients with BPPV is suboptimal. Common ED management processes include brain imaging and treatment with vestibular suppressant medications such as meclizine, neither of which is recommended by current guidelines. The most efficient management of BPPV is to perform a bedside test (Dix-Hallpike test) and then to treat the patients with a bedside positional (the Epley) maneuver. In this practical review we emphasize the efficient management for the most common form of BPPV-posterior canal BPPV. Using this management will reduce resource utilization (laboratory testing, brain imaging, specialist consultation), reduce ED length of stay, and reduce use of ineffective mediations that have side effects but little therapeutic effect. Application of these practices would improve important patient-centered outcomes such as symptom reduction, radiation exposure, side effects from medications, and less need for urgent follow-up with another health care provider. The article also discusses the approach to patients in whom the Dix-Hallpike and/or Epley maneuvers do not seem to work. This includes a discussion the second most common variant of BPPV (horizontal canal BPPV) and criteria for safe discharge of patients. Another important advantage of learning BPPV best practices is that it is enormously satisfying for the clinician, not unlike treating a child with a nursemaid's elbow.
Topics: Child; Humans; Benign Paroxysmal Positional Vertigo; Patient Positioning; Dizziness; Brain; Physicians
PubMed: 35833326
DOI: 10.1111/acem.14558 -
The Journal of Neuroscience : the... Aug 2022Chemotherapy-induced peripheral neuropathy (CIPN) affects ∼68% of patients undergoing chemotherapy, causing debilitating neuropathic pain and reducing quality of life....
Chemotherapy-induced peripheral neuropathy (CIPN) affects ∼68% of patients undergoing chemotherapy, causing debilitating neuropathic pain and reducing quality of life. Cisplatin is a commonly used platinum-based chemotherapeutic drug known to cause CIPN, possibly by causing oxidative stress damage to primary sensory neurons. Metabotropic glutamate receptors (mGluRs) are widely hypothesized to be involved in pain processing and pain mitigation. Meclizine is an H1 histamine receptor antagonist known to have neuroprotective effects, including an anti-oxidative effect. Here, we used a mouse model of cisplatin-induced CIPN using male and female mice to test agonists of mGluR8 and Group II mGluR as well as meclizine as interventions to reduce cisplatin-induced pain. We performed behavioral pain tests, and we imaged Ca activity of the large population of dorsal root ganglia (DRG) neurons For the latter, we used a genetically-encoded Ca indicator, Pirt-GCaMP3, which enabled us to monitor different drug interventions at the level of the intact DRG neuronal ensemble. We found that CIPN increased spontaneous Ca activity in DRG neurons, increased number of Ca transients, and increased hyper-responses to mechanical, thermal, and chemical stimuli. We found that mechanical and thermal pain caused by CIPN was significantly attenuated by the mGluR8 agonist, (S)-3,4-DCPG, the Group II mGluR agonist, LY379268, and the H1 histamine receptor antagonist, meclizine. DRG neuronal Ca activity elevated by CIPN was attenuated by LY379268 and meclizine, but not by (S)-3,4-DCPG. Furthermore, meclizine and LY379268 attenuated cisplatin-induced weight loss. These results suggest that Group II mGluR agonist, mGluR8 agonist, and meclizine are promising candidates as new treatment options for CIPN, and studies of their mechanisms are warranted. Chemotherapy-induced peripheral neuropathy (CIPN) is a painful condition that affects most chemotherapy patients and persists several months or longer after treatment ends. Research on CIPN mechanism is extensive but has produced only few clinically useful treatments. Using GCaMP Ca imaging in live animals over 1800 neurons/dorsal root ganglia (DRG) at once, we have characterized the effects of the chemotherapeutic drug, cisplatin and three treatments that decrease CIPN pain. Cisplatin increases sensory neuronal Ca activity and develops various sensitization. Metabotropic glutamate receptor (mGluR) agonist, LY379268 or the H1 histamine receptor antagonist, meclizine decreases cisplatin's effects on neuronal Ca activity and reduces pain hypersensitivity. Our results and experiments provide insights into cellular effects of cisplatin and drugs preventing CIPN pain.
PubMed: 35772967
DOI: 10.1523/JNEUROSCI.1064-21.2022 -
BMC Pregnancy and Childbirth Jun 2022Women suffering from severe nausea and vomiting during pregnancy, hyperemesis gravidarum, have poor quality of life and increased risk of potentially fatal maternal and...
BACKGROUND
Women suffering from severe nausea and vomiting during pregnancy, hyperemesis gravidarum, have poor quality of life and increased risk of potentially fatal maternal and fetal complications. There is increasing and reassuring knowledge about safety of antiemetics in pregnancy. In 2013, the European Medical Agency (EMA) issued a warning on metoclopramide limiting treatment to maximum five days. Metoclopramide was the most used antiemetic in pregnancy at the time the warning was implemented in the Norwegian hyperemesis guidelines (2014). We aimed at describing changes in the treatment of hyperemesis over time, including changes associated with the EMA warning.
METHODS
Retrospective chart review of all women hospitalized for hyperemesis gravidarum with metabolic disturbances between 01/Jan/2002 and 31/Dec/2019 at a university hospital serving nearly 10% of the pregnant population in Norway. Time-series analysis described changes over time and interrupted time series analysis quantified changes in treatment and clinical outcomes related to the EMA warning.
RESULTS
In total, 1,064 women (1.2% of the birthing population) were included. The use of meclizine, prochlorperazine, and ondansetron increased during 2002-2019. This led to a yearly increase in the percentage of women using any antiemetic of 1.5% (95%CI 0.6; 2.4) pre-hospital, 0.6% (95%CI 0.2; 1.1) during hospitalization, and 2.6% (95%CI 1.3; 3.8) at discharge. Overall, only 50% of the women received antiemetics pre-hospital. Following the EMA warning, prehospital use of metoclopramide dropped by 30% (95%CI 25; 36), while use of any antiemetic pre-hospital dropped by 20% (95%CI 5.7; 34). In timely association, we observed a decrease in gestational age (-3.8 days, 98.75%CI 0.6; 7.1) at first admission, as well as indication of increased rate of termination of pregnancy with an absolute increase of 4.8% (98.75%CI 0.9; 8.7) in 2014.
CONCLUSION
During 2002-2019, the overall use of antiemetics in treatment of hyperemesis increased. The EMA-warning on metoclopramide in 2013 temporarily limited pre-hospital antiemetic provision associated with hospitalization at lower gestational length and indication of an increase in termination of pregnancy.
Topics: Antiemetics; Female; Humans; Hyperemesis Gravidarum; Metoclopramide; Pregnancy; Quality of Life; Retrospective Studies
PubMed: 35655181
DOI: 10.1186/s12884-022-04777-x -
Biomedicines Apr 2022Acne is a chronic inflammatory multifactorial disease involving the anaerobic bacterium Cutibacterium acnes (C. acnes). Current acne treatments are associated with...
Acne is a chronic inflammatory multifactorial disease involving the anaerobic bacterium Cutibacterium acnes (C. acnes). Current acne treatments are associated with adverse effects, limiting treatment compliance and use. We showed that meclozine, an anti-histaminic H1 compound, has anti-inflammatory properties. In Vitro, meclozine reduced the production of CXCL8/IL-8 and IL-1β mRNA and protein by C. acnes-stimulated human keratinocytes and monocytes. No cell toxicity was observed at the IC50. Meclozine prevented the phosphorylation of ERK and JNK. In Vivo, 1% meclozine gel significantly decreased C. acnes-mouse ear induced inflammation by 26.7% (p = 0.021). Ex vivo experiments on human skin explants showed that meclozine decreased the production of GM-CSF, IL-1β and TNF-α at transcriptional and translational levels. In a randomized, double-blind, placebo-controlled proof-of-concept clinical trial on 60 volunteers, 2% meclozine pharmaceutical gel decreased by 20.1% (p < 0.001) the ASI score in the treated group after 12 weeks of treatment. No adverse event was reported. Together, these results indicate that meclozine is a potent topical anti-inflammatory compound of potential value for acne treatment.
PubMed: 35625668
DOI: 10.3390/biomedicines10050931 -
Scientific Reports Apr 2022Repurposing FDA-approved drugs is an efficient and cost-effective approach in the development of therapeutics for a broad range of diseases. However, prediction of...
Repurposing FDA-approved drugs is an efficient and cost-effective approach in the development of therapeutics for a broad range of diseases. However, prediction of function can be challenging, especially in the brain. We screened a small-molecule library with FDA-approved drugs for effects on behavior. The studies were carried out using zebrafish larvae, imaged in a 384-well format. We found that various drugs affect activity, habituation, startle responses, excitability, and optomotor responses. The changes in behavior were organized in behavioral profiles, which were examined by hierarchical cluster analysis. One of the identified clusters includes the calcineurin inhibitors cyclosporine (CsA) and tacrolimus (FK506), which are immunosuppressants and potential therapeutics in the prevention of Alzheimer's disease. The calcineurin inhibitors form a functional cluster with seemingly unrelated drugs, including bromocriptine, tetrabenazine, rosiglitazone, nebivolol, sorafenib, cabozantinib, tamoxifen, meclizine, and salmeterol. We propose that drugs with 'CsA-type' behavioral profiles are promising candidates for the prevention and treatment of Alzheimer's disease.
Topics: Alzheimer Disease; Animals; Calcineurin; Calcineurin Inhibitors; Cluster Analysis; Cyclosporine; Immunosuppressive Agents; Tacrolimus; Zebrafish
PubMed: 35449173
DOI: 10.1038/s41598-022-10133-y -
IScience Mar 2022Multi-step organic syntheses of various drugs, active pharmaceutical ingredients, and other pharmaceutically and agriculturally important compounds have already been... (Review)
Review
Multi-step organic syntheses of various drugs, active pharmaceutical ingredients, and other pharmaceutically and agriculturally important compounds have already been reported using flow synthesis. Compared to batch, hazardous and reactive reagents can be handled safely in flow. This review discusses the pros and cons of flow chemistry in today's scenario and recent developments in flow devices. The review majorly emphasizes on the recent developments in the flow synthesis of pharmaceutically important products in last five years including flibanserin, imatinib, buclizine, cinnarizine, cyclizine, meclizine, ribociclib, celecoxib, SC-560 and mavacoxib, efavirenz, fluconazole, melitracen HCl, rasagiline, tamsulosin, valsartan, and hydroxychloroquine. Critical steps and new development in the flow synthesis of selected compounds are also discussed.
PubMed: 35243250
DOI: 10.1016/j.isci.2022.103892 -
Stem Cell Reports Mar 2022Patients with coronavirus disease 2019 (COVID-19) commonly have manifestations of heart disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome...
Patients with coronavirus disease 2019 (COVID-19) commonly have manifestations of heart disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome encodes 27 proteins. Currently, SARS-CoV-2 gene-induced abnormalities of human heart muscle cells remain elusive. Here, we comprehensively characterized the detrimental effects of a SARS-CoV-2 gene, Orf9c, on human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) by preforming multi-omic analyses. Transcriptomic analyses of hPSC-CMs infected by SARS-CoV-2 with Orf9c overexpression (Orf9c) identified concordantly up-regulated genes enriched into stress-related apoptosis and inflammation signaling pathways, and down-regulated CM functional genes. Proteomic analysis revealed enhanced expressions of apoptotic factors, whereas reduced protein factors for ATP synthesis by Orf9c. Orf9c significantly reduced cellular ATP level, induced apoptosis, and caused electrical dysfunctions of hPSC-CMs. Finally, drugs approved by the U.S. Food and Drug Administration, namely, ivermectin and meclizine, restored ATP levels and ameliorated CM death and functional abnormalities of Orf9c hPSC-CMs. Overall, we defined the molecular mechanisms underlying the detrimental impacts of Orf9c on hPSC-CMs and explored potentially therapeutic approaches to ameliorate Orf9c-induced cardiac injury and abnormalities.
Topics: Action Potentials; Adenosine Triphosphate; Apoptosis; COVID-19; Coronavirus Nucleocapsid Proteins; Down-Regulation; Genome-Wide Association Study; Humans; Ivermectin; Meclizine; Myocytes, Cardiac; Phosphoproteins; Pluripotent Stem Cells; Protein Interaction Maps; RNA, Messenger; SARS-CoV-2; Signal Transduction; Transcriptome; Up-Regulation
PubMed: 35180394
DOI: 10.1016/j.stemcr.2022.01.014