-
Otology & Neurotology : Official... Mar 2023To examine the risk factors for hip fracture in patients with vestibular disorders and the association between antihistamine use and hip fracture in patients with...
OBJECTIVES
To examine the risk factors for hip fracture in patients with vestibular disorders and the association between antihistamine use and hip fracture in patients with vestibular disorders.
STUDY DESIGN
Retrospective case series with chart review.
SETTING
Tertiary academic medical center.
METHODS
A retrospective review of adult patients with hip fracture based on International Classification of Diseases, Tenth Revision (ICD-10) code S72 from January 2013 to December 2019 who had previously been diagnosed with a vestibular disorder based on ICD-10 codes H81-83, A88.1, and R42.
RESULTS
A total of 201 patients were identified meeting the inclusion criteria. The average age at the time of hip fracture was 78.8 years and the majority were female (64.7%). Most patients were diagnosed with nonspecific dizziness (60.2%) or vertigo (23.9%). Those with a peripheral vestibular disorder included benign paroxysmal positional vertigo (BPPV) in 13.4% and Ménière's disease in 2.5%. Overall, meclizine was prescribed to 38.3% of patients, including 29.9% of patients before hip fracture. Meclizine was prescribed to 66.7% of patients with BPPV. Patients were seen for vestibular symptoms 0.67 ± 2.51 years before hip fracture, and 98 patients (48.8%) presented with vestibular concerns within 1 year prior.
CONCLUSION
Patients with vestibular disorders who sustain a ground level fall resulting in hip fracture are a vulnerable population of predominantly older adults with multiple comorbidities. Patients were frequently diagnosed with dizziness or vertigo rather than more specific causes being identified. Multifactorial interventions to prevent hip fractures in older adults have been recommended; however, this study suggests that meclizine use was common among patients diagnosed with dizziness, vertigo, or BPPV before hip fracture.
Topics: Humans; Female; Male; Aged; Dizziness; Meclizine; Retrospective Studies; Vestibular Diseases; Benign Paroxysmal Positional Vertigo; Hip Fractures
PubMed: 36728629
DOI: 10.1097/MAO.0000000000003792 -
Free Radical Biology & Medicine Oct 2016To meet energy demands, dorsal root ganglion (DRG) neurons harbor high mitochondrial content, which renders them acutely vulnerable to disruptions of energy homeostasis....
To meet energy demands, dorsal root ganglion (DRG) neurons harbor high mitochondrial content, which renders them acutely vulnerable to disruptions of energy homeostasis. While neurons typically rely on mitochondrial energy production and have not been associated with metabolic plasticity, new studies reveal that meclizine, a drug, recently linked to modulations of energy metabolism, protects neurons from insults that disrupt energy homeostasis. We show that meclizine rapidly enhances glycolysis in DRG neurons and that glycolytic metabolism is indispensable for meclizine-exerted protection of DRG neurons from hypoxic stress. We report that supplementation of meclizine during hypoxic exposure prevents ATP depletion, preserves NADPH and glutathione stores, curbs reactive oxygen species (ROS) and attenuates mitochondrial clustering in DRG neurites. Using extracellular flux analyzer, we show that in cultured DRG neurons meclizine mitigates hypoxia-induced loss of mitochondrial respiratory capacity. Respiratory capacity is a measure of mitochondrial fitness and cell ability to meet fluctuating energy demands and therefore, a key determinant of cellular fate. While meclizine is an 'old' drug with long record of clinical use, its ability to modulate energy metabolism has been uncovered only recently. Our findings documenting neuroprotection by meclizine in a setting of hypoxic stress reveal previously unappreciated metabolic plasticity of DRG neurons as well as potential for pharmacological harnessing of the newly discovered metabolic plasticity for protection of peripheral nervous system under mitochondria compromising conditions.
Topics: Adenosine Triphosphate; Animals; Astrocytes; Cell Hypoxia; Ganglia, Spinal; Glucose; Glycolysis; Histamine H1 Antagonists; Hydrogen-Ion Concentration; Lactic Acid; Male; Meclizine; Mice; Mice, Inbred C57BL; Mitochondria; Neurons; Oxygen Consumption; Primary Cell Culture; Protective Agents; Stress, Physiological
PubMed: 27458119
DOI: 10.1016/j.freeradbiomed.2016.07.022 -
Scientific Reports Sep 2020This study is based on the QbD development of extended-release (ER) extruded-spheronized pellets of Meclizine HCl and its comparative pharmacokinetic evaluation with...
QbD based Eudragit coated Meclizine HCl immediate and extended release multiparticulates: formulation, characterization and pharmacokinetic evaluation using HPLC-Fluorescence detection method.
This study is based on the QbD development of extended-release (ER) extruded-spheronized pellets of Meclizine HCl and its comparative pharmacokinetic evaluation with immediate-release (IR) pellets. HPLC-fluorescence method was developed and validated for plasma drug analysis. IR drug cores were prepared from lactose, MCC, and PVP using water as granulating fluid. Three-level, three-factor CCRD was applied for modeling and optimization to study the influence of Eudragit (RL100-RS100), TEC, and talc on drug release and sphericity of coated pellets. HPLC-fluorescence method was sensitive with LLOQ 1 ng/ml and linearity between 10 and 200 ng/ml with R > 0.999. Pharmacokinetic parameters were obtained by non-compartmental analysis and results were statistically compared using logarithmically transformed data, where p > 0.05 was considered as non-significant with a 90% CI limit of 0.8-1.25. The AUC and AUC of ER pellets were not significantly different with geometric mean ratio 1.0096 and 1.0093, respectively. The C of IR pellets (98.051 ng/ml) was higher than the ER pellets (84.052 ng/ml) and the T of ER pellets (5.116 h) was higher than the IR pellets (3.029 h). No significant food effect was observed on key pharmacokinetic parameters of ER pellets. Eudragit RL100 (6%) coated Meclizine HCl pellets have a potential therapeutic effect for an extended time period.
Topics: Adult; Anti-Allergic Agents; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Female; Fluorescence; Humans; Male; Meclizine; Polymethacrylic Acids; Young Adult
PubMed: 32913337
DOI: 10.1038/s41598-020-71751-y -
JAMA Nov 1965
Topics: Abnormalities, Drug-Induced; Animals; Cyclizine; Female; Histamine H1 Antagonists; Humans; Legislation as Topic; Meclizine; Piperazines; Pregnancy; United States; United States Food and Drug Administration
PubMed: 4378960
DOI: No ID Found -
Journal of Special Operations Medicine... 2016The series objective is to review various clinical conditions/ presentations, including the latest evidence on management, and to dispel common myths. In the process,... (Review)
Review
The series objective is to review various clinical conditions/ presentations, including the latest evidence on management, and to dispel common myths. In the process, core knowledge and management principles are enhanced. A clinical case will be presented. Cases will be drawn from real life but phrased in a context that is applicable to the Special Operations Forces (SOF) or tactical emergency medical support (TEMS) environment. Details will be presented in such a way that the reader can follow along and identify how they would manage the case clinically depending on their experience and environment situation. Commentary will be provided by currently serving military medical technicians. The medics and author will draw on their SOF experience to communicate relevant clinical concepts pertinent to different operational environments including SOF and TEMS. Commentary and input from active special op.
Topics: Acupressure; Antiemetics; Cholinergic Antagonists; Dopamine Antagonists; Emergency Medical Technicians; Histamine Antagonists; Humans; Meclizine; Metoclopramide; Military Personnel; Motion Sickness; Ondansetron; Promethazine; Scopolamine
PubMed: 27450607
DOI: No ID Found -
Human Molecular Genetics Apr 2016Achondroplasia (ACH) is the prototype and most common of the human chondrodysplasias. It results from gain-of-function mutations that exaggerate the signal output of the... (Review)
Review
Achondroplasia (ACH) is the prototype and most common of the human chondrodysplasias. It results from gain-of-function mutations that exaggerate the signal output of the fibroblast growth factor receptor 3 (FGFR3), a receptor tyrosine kinase that negatively regulates growth plate activity and linear bone growth. Several approaches to reduce FGFR3 signaling by blocking receptor activation or inhibiting downstream signals have been proposed. Five show promise in preclinical mouse studies. Two candidate therapies target the extracellular domain of FGFR3. The first is a decoy receptor that competes for activating ligands. The second is a synthetic blocking peptide that prevents ligands from binding and activating FGFR3. Two established drugs, statins and meclozine, improve growth of ACH mice. The strongest candidate therapy employs an analog of C-type natriuretic peptide (CNP), which antagonizes the mitogen-activated-protein (MAP) kinase pathway downstream of the FGFR3 receptor and may also act independently in the growth plate. Only the CNP analog has reached clinical trials. Preliminary results of Phase 2 studies show a substantial increase in growth rate of ACH children after six months of therapy with no serious adverse effects. A challenge for drug therapy in ACH is targeting agents to the avascular growth plate. The application of gene therapy in osteoarthritis offers insights because it faces similar technical obstacles. Major advances in gene therapy include the emergence of recombinant adeno-associated virus as the vector of choice, capsid engineering to target vectors to specific tissues, and development of methods to direct vectors to articular chondrocytes.
Topics: Achondroplasia; Animals; Genetic Therapy; Humans; Mice; Osteoarthritis
PubMed: 26443596
DOI: 10.1093/hmg/ddv419 -
Chirality Aug 2020Enantiomeric resolution and molecular docking studies of meclizine hydrochloride on polysaccharide-based chiral stationary phase comprising cellulose...
Bioanalytical chiral chromatographic technique and docking studies for enantioselective separation of meclizine hydrochloride: Application to pharmacokinetic study in rabbits.
Enantiomeric resolution and molecular docking studies of meclizine hydrochloride on polysaccharide-based chiral stationary phase comprising cellulose tris(4-methylbenzoate) chiral selector (150 × 4.6 mm, 3.0 μm) were presented. The mobile phase used was acetonitrile:10mM ammonium bicarbonate (95:05, v/v). The developed technique was used to perform the enantioselective assay of meclizine hydrochloride in its marketed formulation. The elution order of meclizine hydrochloride enantiomers was determined by docking studies. Target compound was extracted from rabbit plasma using protein precipitation technique, followed by development of bioanalytical chiral separation method using the same matrix. Application of the method to determine pharmacokinetic parameters of meclizine hydrochloride enantiomers was performed using Phoenix WinNonlin 8.1 software. The results demonstrated stereoselective disposition of meclizine hydrochloride enantiomers in rabbits.
Topics: Animals; Drug Compounding; Meclizine; Molecular Docking Simulation; Rabbits; Stereoisomerism; Tissue Distribution
PubMed: 32567097
DOI: 10.1002/chir.23241 -
Journal of Pharmaceutical Sciences Aug 1973
Topics: Chloroform; Chromatography, Gas; Mathematics; Meclizine; Methods; Solutions; Tablets
PubMed: 4733473
DOI: 10.1002/jps.2600620824 -
Journal of AOAC International Mar 2022Noising is an undesirable phenomenon accompanying the development of widely used chemometric models such as partial least square regression (PLSR) and support vector...
BACKGROUND
Noising is an undesirable phenomenon accompanying the development of widely used chemometric models such as partial least square regression (PLSR) and support vector regression (SVR).
OBJECTIVE
Optimizations of these chemometric models by applying orthogonal projection to latent structures (OPLS) as a preprocessing step which is characterized by canceling noise is the purpose of this research study. Additionally, a comprehensive comparative study between the developed methods was undertaken highlighting pros and cons.
METHODS
OPLS was conducted with PLSR and SVR for quantitative determination of pyridoxine HCl, cyclizine HCl, and meclizine HCl in the presence of their related impurities. The training set was formed from 25 mixtures as there were five mixtures for each compound at each concentration level. Additionally, to check the validity and predictive ability of the developed chemometric models, independent test set mixtures were prepared by repeating the preparation of four mixtures of the training set plus preparation of another four independent mixtures.
RESULTS
Upon application of the OPLS processing method, an upswing of the predictive abilities of PLSR and SVR was found. The root-mean-square error of prediction of the test set was the basic benchmark for comparison.
CONCLUSION
The major finding from the conducted research is that processing with OPLS reinforces the ability of models to anticipate the future samples.
HIGHLIGHTS
Novel optimizations of the widely used chemometric models; application of a comparative study between the suggested methods; application of OPLS preprocessing methods; quantitative determination of pyridoxine HCl, cyclizine HCl and meclizine HCl; checking the predictive power of developed chemometric models; analysis of active ingredients in their pharmaceutical dosage forms.
Topics: Chemometrics; Cyclizine; Least-Squares Analysis; Meclizine; Pyridoxine
PubMed: 34672335
DOI: 10.1093/jaoacint/qsab141 -
Journal of Pharmaceutical Sciences Oct 1985Meclizine, used prophylactically for the prevention of motion sickness and vertigo, is presently available only in oral form. We report herein that, when given... (Comparative Study)
Comparative Study
Meclizine, used prophylactically for the prevention of motion sickness and vertigo, is presently available only in oral form. We report herein that, when given intranasally, meclizine dihydrochloride is absorbed in rats about half as effectively as when given intravenously, but about six times more effectively than after oral administration, as estimated by the area under the plasma concentration-time curve. The mean times to peak levels in plasma are about 8.5 min after an intranasal dose and 49.0 min after oral delivery. We extended these studies to a second species, the beagle dog, and achieved qualitatively similar results with a new formulation (Mecnazone; Nastech Pharmaceutical Co., Inc.). The fraction absorbed intranasally was about 0.89 that of an equivalent intravenous dose but about four times that of an equivalent oral administration. In these studies, the mean times to peak levels in plasma was 11.9 min after an intranasal dose and 70.0 min after an oral dose. Terminal elimination kinetics were the same for all routes within each species. Intranasal delivery of meclizine therefore appears to be superior to the oral route for the more rapid achievement of substantial levels in plasma at a reduced dose.
Topics: Administration, Intranasal; Administration, Oral; Animals; Chromatography, High Pressure Liquid; Dogs; Injections, Intravenous; Kinetics; Meclizine; Rats; Species Specificity
PubMed: 4078711
DOI: 10.1002/jps.2600741022