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International Scholarly Research Notices 2014The intention of present research is to formulate and develop the meclizine hydrochloride fast dissolving tablets using sublimation method to enhance the dissolution...
The intention of present research is to formulate and develop the meclizine hydrochloride fast dissolving tablets using sublimation method to enhance the dissolution rate. In this study an attempt was made to fasten the drug release from the oral tablets by incorporating the superdisintegrants and camphor as sublimating agent. The prepared fast dissolving tablets were subjected to precompression properties and characterized for hardness, weight variation, friability, wetting time, water absorption ratio, and disintegration time. From in vitro release studies, the formulation F9 exhibited fast release profile of about 98.61% in 30 min, and disintegration time 47 sec when compared with other formulations. The percent drug release in 30 min (Q 30) and initial dissolution rate for formulation F9 was 98.61 ± 0.25%, 3.29%/min. These were very much higher compared to marketed tablets (65.43 ± 0.57%, 2.18%/min). The dissolution efficiency was found to be 63.37 and it is increased by 1.4-fold with F9 FDT tablets compared to marketed tablets. Differential scanning calorimetry and Fourier transform infrared spectroscopy studies revealed that there was no possibility of interactions. Thus the development of meclizine hydrochloride fast dissolving tablets by sublimation method is a suitable approach to improve the dissolution rate.
PubMed: 27355021
DOI: 10.1155/2014/281376 -
Tidsskrift For Den Norske Laegeforening... May 2019A woman in her fifties was admitted to hospital with decreased awareness and circulatory failure. She had been treated with left atrial cryoablation a few weeks before...
BACKGROUND
A woman in her fifties was admitted to hospital with decreased awareness and circulatory failure. She had been treated with left atrial cryoablation a few weeks before admission and had been cardioverted a few days after the procedure because of relapse of atrial fibrillation.
CASE PRESENTATION
On admission, the patient had systolic blood pressure of 80 mm Hg and an ECG with broad QRS-complexes at 380 ms. We suspected intoxication and she was intubated to administer activated charcoal after gastric lavage. She was cardiovascularly unstable and in need of intravenous infusion of noradrenaline and adrenaline. Further investigations at her home suggested that she had poisoned herself with 4-5 g flecainide, 0.3 g oxazepam and 0.5 g meclizine. After administration of 500 mmol sodium bicarbonate and 5 mmol calcium chloride, the QRS complexes narrowed temporarily. On day 2, due to sustained bradycardia and hypotension despite receiving adrenergic medications, a temporary pacemaker was implanted, leading to improved heart rate and blood pressure. She experienced several complications including hypertensive pulmonary oedema, atrial fibrillation, extensively prolonged QT interval because of polypharmacy and Takotsubo cardiomyopathy. She was discharged from the hospital in good health on day 17. At a follow-up visit at the outpatient clinic 12 weeks later, cardiac function had normalised. The QT interval was now normal; however, there were persistent T-wave inversions in leads I, aVL and V4-6.
INTERPRETATION
Flecainide blocks sodium channels in cardiomyocytes. Intoxication with flecainide is rare, with mortality rates of about 10 %. Sodium bicarbonate in larger doses has been reported to stabilise patients with flecainide intoxication due to modification of the binding of flecainide to sodium receptors in cardiomyocytes, and due to alkalisation which makes flecainide detach from sodium receptors. Our patient had a temporary effect with narrowing of QRS complexes after receiving sodium bicarbonate. She also showed a beneficial effect from implantation of a temporary pacemaker, although earlier case reports have described problems with high thresholds and capture failure.
Topics: Anti-Arrhythmia Agents; Charcoal; Drug Overdose; Electrocardiography; Female; Flecainide; Humans; Middle Aged; Pacemaker, Artificial; Shock; Sleepiness; Sodium Bicarbonate
PubMed: 31140247
DOI: 10.4045/tidsskr.18.0683 -
Acta Tropica Jul 2019Leishmaniases are infectious diseases caused by protozoan parasites Leishmania and transmitted by sand flies. Drug repurposing is a therapeutic approach that has shown...
Leishmaniases are infectious diseases caused by protozoan parasites Leishmania and transmitted by sand flies. Drug repurposing is a therapeutic approach that has shown satisfactory results in their treatment. Analyses of antihistaminic drugs have revealed their in vitro and in vivo activity against trypanosomatids. In this way, this study evaluated the antileishmanial activity of H1-antihistamines and identified the cellular alterations in Leishmania (L.) infantum. Cinnarizine, cyproheptadine, and meclizine showed activity against promastigotes with 50% inhibitory concentration (IC) values between 10-29 μM. These drugs also demonstrated activity and selectivity against intracellular amastigotes, with IC values between 20-35 μM. Fexofenadine and cetirizine lacked antileishmanial activity against both forms. Mammalian cytotoxicity studies revealed 50% cytotoxic concentration values between 52 - >200 μM. These drugs depolarized the mitochondria membrane of parasites and caused morphological alterations, including mitochondrial damage, disorganization of the intracellular content, and nuclear membrane detachment. In conclusion, the L. infantum death may be ascribed by the subcellular alterations followed by a pronounced decrease in the mitochondrial membrane potential, indicating dysfunction in the respiratory chain upon H1-antihistamine treatment. These H1-antihistamines could be used to explore new routes of cellular death in the parasite and the determination of the targets at a molecular level, would contribute to understanding the potential of these drugs as antileishmanial.
Topics: Animals; Antiprotozoal Agents; Female; Histamine H1 Antagonists; Leishmania infantum; Membrane Potential, Mitochondrial; Mice; Mice, Inbred BALB C
PubMed: 31002807
DOI: 10.1016/j.actatropica.2019.04.017 -
Scandinavian Journal of Primary Health... Mar 2019Hyperemesis gravidarum (HG) affects 0.3-3% of pregnant women and is a leading cause of hospitalization in early pregnancy. The aim of the study was to investigate...
OBJECTIVE
Hyperemesis gravidarum (HG) affects 0.3-3% of pregnant women and is a leading cause of hospitalization in early pregnancy. The aim of the study was to investigate women's treatment and management of HG, as well as the consequences of HG on women's daily life.
DESIGN AND SETTING
A cross-sectional study based on a structured telephone interview and an online questionnaire. Participants were recruited by social media and by the Norwegian patient's organization for HG.
SUBJECTS
Norwegian women that experienced HG.
MAIN OUTCOME MEASURE
Women's perspectives on management and consequences of HG.
RESULTS
The study included 107 women. Maternal morbidity was profound; about 3/4 of participants were hospitalized due to HG, and the majority showed clinical signs of dehydration (79%), ketonuria (75%), and >5% weight loss (84%). Antiemetics were used by >90% and frequently prescribed "as needed". Metoclopramide (71%) and meclozine (51%) were most commonly used. Participants described HG as having severe psychosocial consequences and profound impact on daily activities. Almost two out of five reported thoughts of elective abortion, and 8 women had at least one elective pregnancy termination due to HG. Overall, 20 women (19%) changed GPs due to dissatisfaction with HG management.
CONCLUSION
Despite the high psychosocial burden and major impact on daily activities, many women with HG reported a lack of support from healthcare professionals and suboptimal management. Greater awareness and knowledge among healthcare professionals is needed to improve care for women with HG. Key Points There is a paucity of studies on management and the consequences of HG on women's daily lives and psychosocial burden. We found that: • Many women described HG as one of their worst life experiences with profound morbidity. • Many women reported suboptimal management of HG and lack of support from healthcare professionals. • Greater understanding of patient perspectives among healthcare professionals is important to improve care and management for HG patients.
Topics: Abortion, Induced; Activities of Daily Living; Adult; Antiemetics; Attitude; Cross-Sectional Studies; Dehydration; Emotions; Female; Hospitalization; Humans; Hyperemesis Gravidarum; Ketosis; Meclizine; Metoclopramide; Nausea; Norway; Patient Satisfaction; Pregnancy; Pregnant Women; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Weight Loss
PubMed: 30822254
DOI: 10.1080/02813432.2019.1569424 -
British Journal of Pharmacology Dec 2023Blood-brain barrier (BBB) ABCB1, ABCG2 and ABCC5 transporters influence central therapeutic drug distribution. Transporter expression is regulated by the NR3C1, NR1I3...
BACKGROUND AND PURPOSE
Blood-brain barrier (BBB) ABCB1, ABCG2 and ABCC5 transporters influence central therapeutic drug distribution. Transporter expression is regulated by the NR3C1, NR1I3 and NR1I2 nuclear receptors, but their precise roles in brain are poorly understood. We investigated the effects of selective ligand-based activation of NR3C1, NR1I3, NR1I2 and NR2B1 in porcine brain endothelial cells (PBECs).
EXPERIMENTAL APPROACH
Primary cultures of PBECs were exposed to NR3C1, NR1I3 and NR1I2 ligands and ABCB1, ABCG2 and ABCC5 transporter activities determined by measuring intracellular accumulation of fluorescent probes. Western blotting was used to determine the effects of receptor ligands on expression of ABCB1, ABCG2, ABCC5, NR1I2, NR1I3, NR3C1 and NR2B1. Fluorescent immunocytochemistry was employed to assess the effects of receptor ligands on the cellular localisation of NR1I2 and NR1I3.
KEY RESULTS
The NR1I2 agonist rifampicin significantly up-regulated ABCG2 activity, which is counteracted by co-treatment with NR1I2 antagonist l-sulforaphane. The NR1I3 agonist 6-(4-chlorophenyl)-imidazo[2,1-b]thiazole-5-carbaldehyde and inverse agonist meclizine significantly down-regulated ABCB1, ABCG2 and ABCC5 activity. NR3C1 agonist dexamethasone significantly increased ABCB1, ABCG2 and ABCC5 activity and ABCG2 and ABCC5 protein expression, which was counteracted by co-treatment with the NR3C1 antagonist mifepristone. This first study demonstrates that NR1I3 and NR3C1 regulate ABCC5 activity and protein expression in BBB endothelial cells.
CONCLUSIONS AND IMPLICATIONS
In PBECs, expression of key ATP-binding cassette (ABC) transporters and nuclear receptors is differentially regulated by NR1I3, NR1I2, NR3C1 and NR2B1. This will help to better understand the response of the BBB to physiological and pharmacological activation of nuclear receptors.
Topics: Animals; Swine; Blood-Brain Barrier; ATP-Binding Cassette Transporters; Pregnane X Receptor; Endothelial Cells; Drug Inverse Agonism; Receptors, Cytoplasmic and Nuclear
PubMed: 37476954
DOI: 10.1111/bph.16196 -
Molecular Neurobiology Dec 2017Chemotherapy-induced neurotoxicity of peripheral nervous system (PNS) hinders efficacy of cancer treatments. Mechanisms initiating PNS injury by anticancer drugs are...
Chemotherapy-induced neurotoxicity of peripheral nervous system (PNS) hinders efficacy of cancer treatments. Mechanisms initiating PNS injury by anticancer drugs are incompletely understood delaying development of effective management strategies. To understand events triggered in PNS by cancer drugs, we exposed dorsal root ganglion (DRG) neurons to cisplatin, a drug from platinum-based class of chemotherapeutics frequently implicated in peripheral neuropathies. While cisplatin enters cancer cells and forms cisplatin/DNA crosslinks that block cell proliferation, circulating cisplatin can also reach the PNS and produce crosslinks that impede critical DNA transactions in postmitotic neurons. Cisplatin forms crosslinks with both, nuclear and mitochondrial DNA (mtDNA). Crosslinks are repairable primarily via the nucleotide excision repair (NER) pathway, which is present in nuclei but absent from mitochondrial compartment. Hence, high mitochondrial content and limited shielding by blood nerve barrier make DRG neurons particularly vulnerable to mitochondrial injury by cisplatin. We report that in DRG neurons, cisplatin elevates reactive oxygen species, depletes mtDNA, and impairs mitochondrial respiration, whereas concomitant meclizine supplementation preserves redox balance, attenuates mitochondrial compromise, and augments DNA repair. Meclizine is an antihistamine drug recently implicated in neuroprotection via modulation of energy metabolism. Our data demonstrate that in the mitochondria-rich DRG neurons, meclizine mitigates cisplatin-induced mitochondrial compromise via enhancement of pentose phosphate pathway and repletion of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione stores. The findings suggest that meclizine-mediated preservation of redox balance sustains mitochondrial respiration and supports execution of cellular processes, including timely removal of cisplatin crosslinks from nuclear DNA, thereby attenuating cisplatin toxicity in DRG neurons. Collectively, the findings reveal potential for pharmacologic modulation of dorsal root ganglion neurons metabolism for protection against toxicity of chemotherapeutic drugs.
Topics: Animals; Antineoplastic Agents; Cells, Cultured; Cisplatin; DNA Damage; DNA, Mitochondrial; Ganglia, Spinal; Male; Meclizine; Mice, Inbred C57BL; Mitochondria; Neurons; Peripheral Nervous System; Peripheral Nervous System Diseases; Reactive Oxygen Species
PubMed: 27858292
DOI: 10.1007/s12035-016-0273-9 -
Molecules (Basel, Switzerland) Oct 2023The classical least squares (CLS) model and three augmented CLS models are adopted and validated for the analysis of pyridoxine HCl (PYR), cyclizine HCl (CYC), and...
The classical least squares (CLS) model and three augmented CLS models are adopted and validated for the analysis of pyridoxine HCl (PYR), cyclizine HCl (CYC), and meclizine HCl (MEC) in a quinary mixture with two related impurities: the CYC main impurity, Benzhydrol (BEH), which has carcinogenic and hepatotoxic effects, and the MEC official impurity, 4-Chlorobenzophenone (BEP). The proposed augmented CLS models are orthogonal signal correction CLS (OSC-CLS), direct orthogonal signal correction CLS (DOSC-CLS), and net analyte processing CLS (NAP-CLS). These models were applied to quantify the three active constituents in their raw materials and their corresponding dosage forms using their UV spectra. To evaluate the CLS-based models sensibly, we design a comparative study involving two sets: the training set to construct models and the validation set to assess the prediction abilities of these models. A five-level, five-factor calibration design was established to produce 25 mixtures for the calibration set. In addition, 16 experiments were performed for a test set distributed equally between the in-space and out-space samples. The primary criterion for comparing the models' performance was the validation set's root mean square error of prediction (RMSEP) value. Finally, augmented CLS models showed acceptable results for assaying the three analytes. The results were compared statistically with the reported HPLC methods; however, the DOSC-CLS model proved the best for assaying the dosage forms.
Topics: Antiemetics; Least-Squares Analysis; Meclizine; Calibration; Chromatography, High Pressure Liquid
PubMed: 37894524
DOI: 10.3390/molecules28207044 -
Indian Journal of Otolaryngology and... Apr 2023COVID-19 has infected millions of people worldwide causing millions of deaths. COVID-19 has many serious effects on organs of the body especially the respiratory system...
COVID-19 has infected millions of people worldwide causing millions of deaths. COVID-19 has many serious effects on organs of the body especially the respiratory system causing pneumonia and acute respiratory distress syndrome (ARDS). The disease also has severe complications on other different organs; kidneys and liver which may end in multi-organ failure. Most common symptoms that have been detected in large section of patients were fever, cough and loss of taste or smell and less commonly sore throat, headache and muscle pain. The incidence of vertigo or dizziness is a rare symptom of COVID-19. In this case report, we introduce a 59-year-old male patient suffering from acute vertigo attack after COVID-19 infection. The patient had negative medical history of vertigo and any ear diseases. The patient received REGEN-COV (casirivimab and imdevimab) for COVID-19 and meclizine for vertigo. Vertigo attacks lasted for the two weeks follow up after disappearance of COVID-19 symptoms despite receiving vertigo medication. In conclusion, vertigo may be the sole neurological manifestation of COVID-19. More observational studies should address this symptom and researchers should also focus on identifying the origin of developing vertigo and the direct or indirect mechanisms that SARS-CoV-2 triggers to develop dizziness in general. This research should deliver a clear message, especially to ER physicians to consider proper referral of these patients without underestimating the risk of developing more serious COVID-19 symptoms as ARDS and multi-organ failure if no proper testing and follow-up are provided.
PubMed: 37362121
DOI: 10.1007/s12070-023-03745-x -
International Journal of Pharmaceutics Dec 2015Oral thin film (OTF) is a preparation of postage stamp size, with advantages of flexible, tasty and without water for oral administration. A commercial product...
Oral thin film (OTF) is a preparation of postage stamp size, with advantages of flexible, tasty and without water for oral administration. A commercial product (Zentrip®) was developed for people who suffered from motion sickness. In order to improve the mechanical strength of Zentrip®, OTF containing meclizine hydrochloride (MH) was designed and prepared using the solvent casting method. The characteristics of the prepared OTF were evaluated using micrometer, auto stripping tester, DSC, X-ray diffraction. ATR-FTIR was employed to investigate the interaction between drug and polymer. The thickness of MH OTF obtained was 0.116±0.004mm, the tensile strength was 17.37±1.54Nmm(-2) and the drug dissolution at 5min was more than 80% both in distilled water and 0.1mol/L HCL. DSC and XRD showed MH was amorphous in the polymer. ATR-FTIR indicated the MH molecules inserted into the network structure of polymer, which resulted in an inhibition of drug recrystallization. The Cmax of Zentrip® and MH OTF were 1.46±0.44μg/mL and 1.91±0.51μg/mL, and the AUC were 10.38±2.93μgh/mL and 13.74±3.23μgh/mL, respectively. Compared with Zentrip®, MH OTF successfully overcome the weakness of mechanical strength, possessed faster dissolution profile and showed bioequivalence in pharmacokinetics, deserving to a further development.
Topics: Administration, Oral; Animals; Drug Carriers; Drug Compounding; Drug Evaluation, Preclinical; Male; Meclizine; Rats; Rats, Wistar; Tensile Strength; X-Ray Diffraction
PubMed: 26456247
DOI: 10.1016/j.ijpharm.2015.10.008 -
The Consultant Pharmacist : the Journal... Apr 2015Few studies have examined racial differences in potentially inappropriate medication use. The objective of this study was to examine racial disparities in using...
OBJECTIVE
Few studies have examined racial differences in potentially inappropriate medication use. The objective of this study was to examine racial disparities in using prescription and/or nonprescription anticholinergics, a type of potentially inappropriate medication, over time.
DESIGN
Longitudinal.
SETTING
Data from the Health, Aging, and Body Composition Study (years 1, 5, and 10).
PARTICIPANTS
Three thousand fifty-five community-dwelling older adults, both blacks and whites, at year 1.
MAIN OUTCOME MEASURE
Highly anticholinergic medication use per the 2012 American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.
RESULTS
Blacks represented 41.4% of the participants at year 1. At year 1, 13.4% of blacks used an anticholinergic medication compared with 17.8% of whites, and this difference persisted over the ensuing 10-year period. Diphenhydramine was the most common anticholinergic medication reported at baseline and year 5, and meclizine at year 10, for both races. Controlling for demographics, health status, and access to care factors, blacks were 24% to 45% less likely to use any anticholinergics compared with whites over the years considered (all P < 0.05).
CONCLUSION
The use of prescription and/or nonprescription anticholinergic medications was less common in older blacks than whites over a 10-year period, and the difference was unexplained by demographics, health status, and access to care.
Topics: Aged; Black People; Cholinergic Antagonists; Drug Utilization; Female; Humans; Male; White People
PubMed: 25893702
DOI: 10.4140/TCP.n.2015.240