Impact of Anticholinergic Medication on Salivary Function; Exploring Potential Genetic Markers for Dry Mouth
抗胆碱能药物对唾液腺功能的影响;
基本信息
- 批准号:10283183
- 负责人:
- 金额:$ 12.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-13 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAdultAdverse effectsAffectAffinityAgeAllelesAnti-CholinergicsAntidepressive AgentsAppointmentAustraliaBiological AssayBloodCYP2C19 geneCYP2D6 geneChemosensitizationCholinergic ReceptorsClinicalClinical ResearchClinical TreatmentClinical TrialsCytochrome P450CytochromesDNADataDeglutitionDeliriumDementiaDentalDental cariesDevelopmentDrug PrescriptionsDrynessDyskinetic syndromeElderlyEnzymesEquipment and supply inventoriesEuropeFeelingFrequenciesFutureGeneticGenetic MarkersGenetic PolymorphismGenetic VariationGoalsGoldHealthImpaired cognitionImpairmentIndividual DifferencesInfectionIntakeInvestigationLeadLiverMasticationMeasurementMeasuresMemory impairmentMetabolicMinor salivary gland structureMonitorMucous MembraneMuscarinic Acetylcholine ReceptorMuscarinicsNeurologicNorth AmericaOralOral Health Impact ProfileOral cavityOral healthOrganOutcomeParasympathetic Nervous SystemPatientsPeripheralPharmaceutical PreparationsPharmacogeneticsPhenotypePolypharmacyPopulationPredispositionPrevalencePreventionPropertyProphylactic treatmentProspective cohort studyPsychosesQuality of lifeQuestionnairesRandomizedReportingResearchRiskRoleSalivaSalivarySalivary GlandsSerumSeveritiesSignal TransductionSpasmolyticsSurveysSymptomsTestingTooth LossToxic effectUpper Respiratory InfectionsUpper respiratory tractVariantVisitXerostomiaage effectaging populationbasecholinergicclinically relevantcurative treatmentsdesigndouble-blind placebo controlled trialdrug metabolismearly screeninggenetic variantgenotyped patientshigh riskinter-individual variationmiddle ageneuroregulationneurotransmissionpersonalized medicinepoint of carepoint of care testingprospectivereceptorrecruitrisk predictionsaliva secretionscreeningside effectsoft tissuetreatment strategyurinary
项目摘要
The growing medication use in all ages led to the fact that 20% of the US adult population take five or more
drugs (polypharmacy). Over 500 medications commonly prescribed in polypharmacy (e.g., antidepressants,
urinary antispasmodics, and psycholeptics) possess anticholinergic (AC) properties blocking the muscarinic
signaling of neural regulation. Due to the scattered distribution of muscarinic receptors in the body, AC
medications have a wide range of side effects. Besides the most severe central toxicity of cognitive impairment,
dyskinesia, and psychosis, which can lead to delirium, the most frequent peripheral side effect is dry mouth. Dry
mouth is characterized by reduced saliva secretion (hyposalivation), impaired quality of life by causing chewing
or swallowing problems, complaints of oral dryness (xerostomia), speaking difficulties, mucosal changes,
increased rate of dental caries, and tooth loss. Dry mouth causes increased susceptibility to bacterial colonization
and infections in the oral cavity and the upper respiratory tract. However, no data are available on predicting
medication-induced dry mouth severity or determining the AC burden from these medications among dental
patients. There is a significant research gap in identifying high-risk xerostomia patients in the middle-aged
population before reaching older ages when damage to oral health is irreversible. We designed a prospective
cohort study with two aims for addressing these questions. In Aim 1., we will evaluate the correlation between
AC burden and dry mouth outcomes, including the flow rates of the minor salivary glands (SG) in 90 middle-
aged patients (45-64 years). We will determine whether high AC burden, quantified by the AC drug score (ADS)
and serum AC activity (SAA) in blood, is associated with more severe dry mouth symptoms, measured at
baseline and follow-ups for two years. We will assess dry mouth using saliva flow rates (unstimulated whole
saliva and minor SGs) and oral health measures associated with dry mouth, including xerostomia, dental caries,
and oral health impact profile. In this aim, we will examine the feasibility of minor SG flow screening as a point-
of-care test for dry mouth. In Aim 2., we will explore whether CYP450 genetic polymorphisms predict dry mouth
severity. Recent studies reported an increased prevalence of AC side effects in patients with inactive genetic
variants of liver cytochrome P450 enzymes responsible for the metabolic clearance of AC drugs. We will analyze
DNA from patients’ blood for the genetic variations of CYP2D6 and CYP2C19 enzymes and compare oral health
outcomes associated with dry mouth between poor and normo-metabolizing phenotypes. We propose to study
whether dry-mouth pharmacogenetics provides evidence for inter-individual variability in oral health outcomes to
identify patients with predictable severity of AC medication-induced dry mouth. The overarching goal of our
explorative study is to establish clinically relevant associations between AC burden and oral health outcomes,
which can support future investigations of potential causal relationships and risk calculations for dry mouth
development.
各个年龄段的药物使用量都在增长,导致20%的美国成年人服用五种或更多的药物
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Szilvia Arany其他文献
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{{ truncateString('Szilvia Arany', 18)}}的其他基金
Impact of Anticholinergic Medication on Salivary Function; Exploring Potential Genetic Markers for Dry Mouth
抗胆碱能药物对唾液腺功能的影响;
- 批准号:
10450110 - 财政年份:2021
- 资助金额:
$ 12.76万 - 项目类别:
Impact of Anticholinergic Medication on Salivary Function; Exploring Potential Genetic Markers for Dry Mouth
抗胆碱能药物对唾液腺功能的影响;
- 批准号:
10650163 - 财政年份:2021
- 资助金额:
$ 12.76万 - 项目类别:
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