{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T13:51:29Z","timestamp":1765374689539,"version":"3.46.0"},"reference-count":91,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Florida Corridor Undergraduate Research Initiative 2024"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Dexmedetomidine is a commonly used sedative because it has minimal adverse effects on respiratory function. Nevertheless, its cardiovascular safety profile, particularly bradycardia risk and drug\u2013drug interactions (DDIs), remains incompletely understood. Additionally, current studies, including our previous analysis using the FDA adverse event reporting system (FAERS), hold several limitations. In this study, the electronic health record (EHR) platform TriNetX was utilized for pharmacovigilance analyses of dexmedetomidine. The significantly elevated incidence of bradycardia in dexmedetomidine-treated patients was demonstrated compared to other prevalent anesthetics. Age-stratified analyses revealed pronounced susceptibility in geriatric patients, while a slightly increased susceptibility in male patients was observed. In addition, elevated DDIs of dexmedetomidine with risperidone and albuterol were identified using disproportionality analysis with propensity score matching. Finally, to investigate molecular mechanisms of dexmedetomidine-associated bradycardia, analyses were conducted on a public microarray dataset, and nine differentially expressed miRNAs were identified following dexmedetomidine administration. Gene Ontology (GO) analysis of target genes of all five up-regulated miRNAs revealed rhythmic process and muscle tissue development as potential explanations. Notably, the target genes of the up-regulated miRNAs miR-26a-5p and miR-30c-5p were significantly enriched in GO terms associated with bradycardia. Together, this study identified bradycardia as a significant adverse drug event (ADE) of dexmedetomidine administration, observed possible clinically meaningful DDIs with dexmedetomidine, demonstrated a greater risk in elderly patients, and provided transcriptomic evidence that miRNA-mediated pathway dysregulation may contribute to dexmedetomidine-associated bradycardia.<\/jats:p>","DOI":"10.3390\/cimb47121028","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T12:20:57Z","timestamp":1765369257000},"page":"1028","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Dexmedetomidine-Associated Bradycardia and Related Drug\u2013Drug Interactions Using Electronic Health Record (EHR) and miRNA Target Analysis"],"prefix":"10.3390","volume":"47","author":[{"given":"Xinran","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Science, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3438-9340","authenticated-orcid":false,"given":"Suguna Aishwarya","family":"Kuppa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Bui","sequence":"additional","affiliation":[{"name":"Department of Mathematics & Statistics, College of Art and Science, University of South Florida, Tampa, FL 33620, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8285-5528","authenticated-orcid":false,"given":"Xiaoming","family":"Liu","sequence":"additional","affiliation":[{"name":"Genomics Center, College of Public Health, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8023-8470","authenticated-orcid":false,"given":"Angela","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapeutics & Clinical Research, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3619-8090","authenticated-orcid":false,"given":"Feng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kong, H., Li, M., Deng, C.M., Wu, Y.J., He, S.T., and Mu, D.L. (2023). A comprehensive overview of clinical research on dexmedetomidine in the past 2 decades: A bibliometric analysis. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1043956"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.4103\/0259-1162.94750","article-title":"Current role of dexmedetomidine in clinical anesthesia and intensive care","volume":"5","author":"Kaur","year":"2011","journal-title":"Anesth. Essays Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"689","DOI":"10.2147\/TCRM.S471229","article-title":"Impact of Dexmedetomidine on Hemodynamics, Plasma Catecholamine Levels, and Delirium Incidence Among Intubated Patients in the ICU\u2014A Randomized Controlled Trial","volume":"20","author":"Qiao","year":"2024","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0014-2999(95)00417-J","article-title":"Action of dexmedetomidine on rat locus coeruleus neurones: Intracellular recording in vitro","volume":"285","author":"Chiu","year":"1995","journal-title":"Eur. J. Pharmacol."},{"key":"ref_5","first-page":"13","article-title":"Dexmedetomidine: A novel sedative-analgesic agent","volume":"14","author":"Gertler","year":"2001","journal-title":"Proc. (Bayl. Univ. Med. Cent.)"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.jemermed.2022.01.017","article-title":"Procedural Sedation with Dexmedetomidine in Combination with Ketamine in the Emergency Department","volume":"63","author":"Henrie","year":"2022","journal-title":"J. Emerg. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0140-6736(20)30631-0","article-title":"Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): A randomised placebo-controlled trial","volume":"396","author":"Turan","year":"2020","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1007\/s12630-019-01440-6","article-title":"Perioperative dexmedetomidine reduces delirium in elderly patients after non-cardiac surgery: A systematic review and meta-analysis of randomized-controlled trials","volume":"66","author":"Pan","year":"2019","journal-title":"Can. J. Anaesth."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4694","DOI":"10.1097\/JS9.0000000000002536","article-title":"Dexmedetomidine for cancer pain: Mechanisms and opioid-sparing effects","volume":"111","author":"Liao","year":"2025","journal-title":"Int. J. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ke, H.H., Liou, J.Y., Teng, W.N., Hsu, P.K., Tsou, M.Y., Chang, W.K., and Ting, C.K. (2023). Opioid-sparing anesthesia with dexmedetomidine provides stable hemodynamic and short hospital stay in non-intubated video-assisted thoracoscopic surgery: A propensity score matching cohort study. BMC Anesthesiol., 23.","DOI":"10.1186\/s12871-023-02032-0"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tsivitis, A., Wang, A., Murphy, J., Khan, A., Jin, Z., Moore, R., Tateosian, V., and Bergese, S. (2023). Anesthesia, the developing brain, and dexmedetomidine for neuroprotection. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1150135"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/ALN.0000000000000951","article-title":"Dexmedetomidine versus Propofol Sedation Reduces Delirium after Cardiac Surgery: A Randomized Controlled Trial","volume":"124","author":"Djaiani","year":"2016","journal-title":"Anesthesiology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/s40265-015-0419-5","article-title":"Dexmedetomidine: A Review of Its Use for Sedation in the Intensive Care Setting","volume":"75","author":"Keating","year":"2015","journal-title":"Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"77","DOI":"10.2147\/OAEM.S17429","article-title":"Sedation with dexmedetomidine in the intensive care setting","volume":"3","author":"Gerlach","year":"2011","journal-title":"Open Access Emerg. Med."},{"key":"ref_15","first-page":"GE01","article-title":"Dexmedetomidine in current anaesthesia practice\u2014A review","volume":"8","author":"Naaz","year":"2014","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"323","DOI":"10.4097\/kja.19259","article-title":"Dexmedetomidine: Present and future directions","volume":"72","author":"Lee","year":"2019","journal-title":"Korean J. Anesthesiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yoshikawa, Y., Hirata, N., Terada, H., Sawashita, Y., and Yamakage, M. (2019). Identification of Candidate Genes and Pathways in Dexmedetomidine-Induced Cardioprotection in the Rat Heart by Bioinformatics Analysis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071614"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s40262-017-0507-7","article-title":"Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine","volume":"56","author":"Weerink","year":"2017","journal-title":"Clin. Pharmacokinet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2344\/0003-3006-62.1.31","article-title":"Alpha-2 adrenergic receptor agonists: A review of current clinical applications","volume":"62","author":"Giovannitti","year":"2015","journal-title":"Anesth. Prog."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1111\/1440-1681.12791","article-title":"Dexmedetomidine protects mice against myocardium ischaemic\/reperfusion injury by activating an AMPK\/PI3K\/Akt\/eNOS pathway","volume":"44","author":"Sun","year":"2017","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chang, J.H., Jin, M.M., and Liu, J.T. (2020). Dexmedetomidine pretreatment protects the heart against apoptosis in ischemia\/reperfusion injury in diabetic rats by activating PI3K\/Akt signaling in vivo and in vitro. Biomed. Pharmacother., 127.","DOI":"10.1016\/j.biopha.2020.110188"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1213\/ANE.0000000000006869","article-title":"Association of Early Dexmedetomidine Utilization with Clinical Outcomes After Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study","volume":"139","author":"Liu","year":"2024","journal-title":"Anesth. Analg."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Benneyworth, B.D., Downs, S.M., and Nitu, M. (2015). Retrospective Evaluation of the Epidemiology and Practice Variation of Dexmedetomidine Use in Invasively Ventilated Pediatric Intensive Care Admissions, 2007\u20132013. Front. Pediatr., 3.","DOI":"10.3389\/fped.2015.00109"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7507","DOI":"10.2147\/JIR.S346089","article-title":"Recent Advances in the Clinical Value and Potential of Dexmedetomidine","volume":"14","author":"Liu","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1592\/phco.27.3.351","article-title":"Adjunctive dexmedetomidine therapy in the intensive care unit: A retrospective assessment of impact on sedative and analgesic requirements, levels of sedation and analgesia, and ventilatory and hemodynamic parameters","volume":"27","author":"MacLaren","year":"2007","journal-title":"Pharmacotherapy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"998","DOI":"10.3349\/ymj.2016.57.4.998","article-title":"Intranasally Administered Adjunctive Dexmedetomidine Reduces Perioperative Anesthetic Requirements in General Anesthesia","volume":"57","author":"Wu","year":"2016","journal-title":"Yonsei Med. J."},{"key":"ref_27","first-page":"30","article-title":"Evaluation of adverse events noted in children receiving continuous infusions of dexmedetomidine in the intensive care unit","volume":"15","author":"Honey","year":"2010","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e31306","DOI":"10.1097\/MD.0000000000031306","article-title":"Risk factors for dexmedetomidine-associated bradycardia during spinal anesthesia: A retrospective study","volume":"101","author":"Kim","year":"2022","journal-title":"Medicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3349\/ymj.2024.0299","article-title":"Dexmedetomidine in Mechanically Ventilated Critically Ill Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"66","author":"Lee","year":"2025","journal-title":"Yonsei Med. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"615","DOI":"10.3390\/genes16060615","article-title":"The Association Between Dexmedetomidine and Bradycardia: An Analysis of FDA Adverse Event Reporting System (FAERS) Data and Transcriptomic Profiles","volume":"16","author":"Morris","year":"2025","journal-title":"Genes"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"P\u00f6yhi\u00e4, R., Nieminen, T., Tuompo, V.W.T., and Parikka, H. (2022). Effects of Dexmedetomidine on Basic Cardiac Electrophysiology in Adults; a Descriptive Review and a Prospective Case Study. Pharmaceuticals, 15.","DOI":"10.3390\/ph15111372"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Shuai, Y., Chen, Z., Wan, Q., Wu, J., and Wang, X. (2024). Dexmedetomidine: A real-world safety analysis based on FDA adverse event reporting system database. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1419196"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1097\/FJC.0000000000001196","article-title":"Effect of Dexmedetomidine on Tachyarrhythmias After Cardiac Surgery: A Systematic Review and Meta-Analysis","volume":"79","author":"Wang","year":"2022","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5158362","DOI":"10.1155\/2022\/5158362","article-title":"Dexmedetomidine Reduces Incidences of Ventricular Arrhythmias in Adult Patients: A Meta-Analysis","volume":"2022","author":"Zhong","year":"2022","journal-title":"Cardiol. Res. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.tcm.2019.07.001","article-title":"Evaluating and management bradycardia","volume":"30","author":"Sidhu","year":"2020","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1136\/qshc.2002.004473","article-title":"Crisis management during anaesthesia: Cardiac arrest","volume":"14","author":"Runciman","year":"2005","journal-title":"Qual. Saf. Health Care"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/acem.12875","article-title":"Incidence of Adverse Events in Adults Undergoing Procedural Sedation in the Emergency Department: A Systematic Review and Meta-analysis","volume":"23","author":"Bellolio","year":"2016","journal-title":"Acad. Emerg. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1213\/ANE.0000000000005843","article-title":"The Effect of Dexmedetomidine on Postanesthesia Care Unit Discharge and Recovery: A Systematic Review and Meta-Analysis","volume":"134","author":"Sin","year":"2022","journal-title":"Anesth. Analg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1016\/j.chest.2020.12.052","article-title":"Safety and Efficacy of Dexmedetomidine in Acutely Ill Adults Requiring Noninvasive Ventilation: A Systematic Review and Meta-analysis of Randomized Trials","volume":"159","author":"Lewis","year":"2021","journal-title":"Chest"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"109849","DOI":"10.1016\/j.jclinane.2020.109849","article-title":"Intravenous administration of dexmedetomidine and quality of recovery after elective surgery in adult patients: A meta-analysis of randomized controlled trials","volume":"65","author":"Miao","year":"2020","journal-title":"J. Clin. Anesth."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3000605211014294","DOI":"10.1177\/03000605211014294","article-title":"Effects of dexmedetomidine on neurocognitive disturbance after elective non-cardiac surgery in senile patients: A systematic review and meta-analysis","volume":"49","author":"Bi","year":"2021","journal-title":"J. Int. Med. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e37283","DOI":"10.2196\/37283","article-title":"The Value of Electronic Health Records Since the Health Information Technology for Economic and Clinical Health Act: Systematic Review","volume":"10","author":"Modi","year":"2022","journal-title":"JMIR Med. Inform."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1001\/jama.2025.7200","article-title":"Dexmedetomidine- or Clonidine-Based Sedation Compared with Propofol in Critically Ill Patients: The A2B Randomized Clinical Trial","volume":"334","author":"Walsh","year":"2025","journal-title":"JAMA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s13054-023-04431-8","article-title":"Propofol and survival: An updated meta-analysis of randomized clinical trials","volume":"27","author":"Kotani","year":"2023","journal-title":"Crit. Care"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13054-024-04831-4","article-title":"Ketamine versus etomidate as an induction agent for tracheal intubation in critically ill adults: A Bayesian meta-analysis","volume":"28","author":"Koroki","year":"2024","journal-title":"Crit. Care"},{"key":"ref_46","first-page":"2266","article-title":"Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies","volume":"28","author":"Guo","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.bja.2023.10.011","article-title":"The MAGIC trial: A pragmatic, multicentre, parallel, noninferiority, randomised trial of melatonin versus midazolam in the premedication of anxious children attending for elective surgery under general anaesthesia","volume":"132","author":"Bolt","year":"2024","journal-title":"Br. J. Anaesth."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Perets, O., Stagno, E., Yehuda, E.B., McNichol, M., Anthony Celi, L., Rappoport, N., and Dorotic, M. (2024). Inherent Bias in Electronic Health Records: A Scoping Review of Sources of Bias. medRxiv.","DOI":"10.1101\/2024.04.09.24305594"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s41666-023-00153-2","article-title":"Biases in Electronic Health Records Data for Generating Real-World Evidence: An Overview","volume":"8","author":"Leviton","year":"2024","journal-title":"J. Healthc. Inform. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1016\/S0735-1097(03)00418-2","article-title":"Effects of aging on cardiovascular responses to parasympathetic withdrawal","volume":"41","author":"Stratton","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1152\/japplphysiol.00601.2003","article-title":"Invited review: Aging and the cardiovascular system","volume":"95","author":"Ferrari","year":"2003","journal-title":"J. Appl. Physiol. (1985)"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1007\/s11357-022-00616-1","article-title":"The role of age-associated autonomic dysfunction in inflammation and endothelial dysfunction","volume":"44","author":"Jiang","year":"2022","journal-title":"Geroscience"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Yeh, C.H., Kuo, T.B.J., Li, J.Y., Kuo, K.L., Chern, C.M., Yang, C.C.H., and Huang, H.Y. (2022). Effects of age and sex on vasomotor activity and baroreflex sensitivity during the sleep-wake cycle. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-26440-3"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"18011","DOI":"10.1073\/pnas.1308477110","article-title":"Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate","volume":"110","author":"Larson","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","first-page":"76","article-title":"The role of extracellular matrix in age-related conduction disorders: A forgotten player?","volume":"12","author":"Spadaccio","year":"2015","journal-title":"J. Geriatr. Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1146\/annurev-physiol-021119-034453","article-title":"Cardiac Pacemaker Activity and Aging","volume":"82","author":"Peters","year":"2020","journal-title":"Annu. Rev. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e14309","DOI":"10.1111\/acel.14309","article-title":"Aging-associated atrial fibrillation: A comprehensive review focusing on the potential mechanisms","volume":"23","author":"Wang","year":"2024","journal-title":"Aging Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/S0531-5565(03)00133-5","article-title":"When drug therapy gets old: Pharmacokinetics and pharmacodynamics in the elderly","volume":"38","author":"Turnheim","year":"2003","journal-title":"Exp. Gerontol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/03602530902722679","article-title":"Pharmacokinetics and drug metabolism in the elderly","volume":"41","author":"Klotz","year":"2009","journal-title":"Drug Metab. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/gerona\/glr118","article-title":"Drug metabolism in older people\u2014A key consideration in achieving optimal outcomes with medicines","volume":"67","author":"McLachlan","year":"2012","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1080\/17425255.2021.1839413","article-title":"Alterations in drug disposition in older adults: A focus on geriatric syndromes","volume":"17","author":"Maher","year":"2021","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Sheikh-Taha, M., and Asmar, M. (2021). Polypharmacy and severe potential drug-drug interactions among older adults with cardiovascular disease in the United States. BMC Geriatr., 21.","DOI":"10.1186\/s12877-021-02183-0"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Delara, M., Murray, L., Jafari, B., Bahji, A., Goodarzi, Z., Kirkham, J., Chowdhury, M., and Seitz, D.P. (2022). Prevalence and factors associated with polypharmacy: A systematic review and Meta-analysis. BMC Geriatr., 22.","DOI":"10.1186\/s12877-022-03279-x"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.cger.2012.07.003","article-title":"Epidemiology of arrhythmias and conduction disorders in older adults","volume":"28","author":"Chow","year":"2012","journal-title":"Clin. Geriatr. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s00213-013-3192-8","article-title":"Risperidone, QTc interval prolongation, and torsade de pointes: A systematic review of case reports","volume":"228","author":"Vieweg","year":"2013","journal-title":"Psychopharmacology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1097\/00005344-200306000-00016","article-title":"Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current","volume":"41","author":"Drolet","year":"2003","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Xiao, Y., Li, J., Qiu, L., Jiang, C., Huang, Y., Liu, J., Sun, Q., Hong, H., and Ye, L. (2021). Dexmedetomidine Protects Human Cardiomyocytes Against Ischemia-Reperfusion Injury Through \u03b12-Adrenergic Receptor\/AMPK-Dependent Autophagy. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.615424"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9369","DOI":"10.1080\/21655979.2022.2054762","article-title":"Dexmedetomidine prevents cardiomyocytes from hypoxia\/reoxygenation injury via modulating tetmethylcytosine dioxygenase 1-mediated DNA demethylation of Sirtuin1","volume":"13","author":"Wang","year":"2022","journal-title":"Bioengineered"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"104589","DOI":"10.1016\/j.phrs.2019.104589","article-title":"Exploring mechanisms of increased cardiovascular disease risk with antipsychotic medications: Risperidone alters the cardiac proteomic signature in mice","volume":"152","author":"Beauchemin","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1093\/ajhp\/60.19.1971","article-title":"Changes in heart rate associated with nebulized racemic albuterol and levalbuterol in intensive care patients","volume":"60","author":"Lam","year":"2003","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1345\/aph.1S003","article-title":"A comparison of heart rate changes associated with levalbuterol and racemic albuterol in pediatric cardiology patients","volume":"47","author":"Kelly","year":"2013","journal-title":"Ann. Pharmacother."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1046\/j.1442-200X.2001.01471.x","article-title":"Standard dose of inhaled albuterol significantly increases QT dispersion compared to low dose of albuterol plus ipratropium bromide therapy in moderate to severe acute asthma attacks in children","volume":"43","author":"Coskun","year":"2001","journal-title":"Pediatr. Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1542\/hpeds.2021-006265","article-title":"Hypokalemia Measurement and Management in Patients with Status Asthmaticus on Continuous Albuterol","volume":"12","author":"Cox","year":"2022","journal-title":"Hosp. Pediatr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.tcm.2014.06.003","article-title":"An emerging role for the miR-26 family in cardiovascular disease","volume":"24","author":"Icli","year":"2014","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/s12276-021-00665-0","article-title":"MicroRNA-26a\/b-5p promotes myocardial infarction-induced cell death by downregulating cytochrome c oxidase 5a","volume":"53","author":"Jung","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1002\/cbin.11685","article-title":"MiR-26a-5p alleviates cardiac hypertrophy and dysfunction via targeting ADAM17","volume":"45","author":"Shi","year":"2021","journal-title":"Cell Biol. Int."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Xing, X., Guo, S., Zhang, G., Liu, Y., Bi, S., Wang, X., and Lu, Q. (2020). miR-26a-5p protects against myocardial ischemia\/reperfusion injury by regulating the PTEN\/PI3K\/AKT signaling pathway. Braz. J. Med. Biol. Res., 53, Erratum in Braz. J. Med. Biol. Res. 2020, 53, e9106erratum.","DOI":"10.1590\/1414-431x20199106"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"100131","DOI":"10.1016\/j.labinv.2023.100131","article-title":"MicroRNA-26a-5p Restoration Ameliorates Unilateral Ureteral Obstruction-Induced Renal Fibrosis in Mice Through Modulating TGF-\u03b2 Signaling","volume":"103","author":"Chung","year":"2023","journal-title":"Lab. Investig."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e70068","DOI":"10.1096\/fj.202400546RR","article-title":"MCPIP1 promotes atrial remodeling by exacerbating miR-26a-5p\/FRAT\/Wnt axis-mediated atrial fibrosis in a rat model susceptible to atrial fibrillation","volume":"38","author":"Li","year":"2024","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Boxhammer, E., Paar, V., Wernly, B., Kiss, A., Mirna, M., Aigner, A., Acar, E., Watzinger, S., Podesser, B.K., and Zauner, R. (2023). MicroRNA-30d-5p-A Potential New Therapeutic Target for Prevention of Ischemic Cardiomyopathy after Myocardial Infarction. Cells, 12.","DOI":"10.3390\/cells12192369"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Kim, J.O., Park, J.H., Kim, T., Hong, S.E., Lee, J.Y., Nho, K.J., Cho, C., Kim, Y.S., Kang, W.S., and Ahn, Y. (2018). A novel system-level approach using RNA-sequencing data identifies miR-30-5p and miR-142a-5p as key regulators of apoptosis in myocardial infarction. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-33020-x"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/kjm2.12309","article-title":"Critical functions of microRNA-30a-5p-E2F3 in cardiomyocyte apoptosis induced by hypoxia\/reoxygenation","volume":"37","author":"Lv","year":"2021","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Zhang, X., Dong, S., Jia, Q., Zhang, A., Li, Y., Zhu, Y., Lv, S., and Zhang, J. (2019). The microRNA in ventricular remodeling: The miR-30 family. Biosci. Rep., 39.","DOI":"10.1042\/BSR20190788"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"eaav1741","DOI":"10.1126\/science.aav1741","article-title":"The biochemical basis of microRNA targeting efficacy","volume":"366","author":"McGeary","year":"2019","journal-title":"Science"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1101\/gr.082701.108","article-title":"Most mammalian mRNAs are conserved targets of microRNAs","volume":"19","author":"Friedman","year":"2009","journal-title":"Genome Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Vacchi-Suzzi, C., Hahne, F., Scheubel, P., Marcellin, M., Dubost, V., Westphal, M., Boeglen, C., B\u00fcchmann-M\u00f8ller, S., Cheung, M.S., and Cordier, A. (2013). Heart structure-specific transcriptomic atlas reveals conserved microRNA-mRNA interactions. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0052442"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/00273171.2011.568786","article-title":"An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies","volume":"46","author":"Austin","year":"2011","journal-title":"Multivar. Behav. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/EDE.0b013e3181a663cc","article-title":"High-dimensional propensity score adjustment in studies of treatment effects using health care claims data","volume":"20","author":"Schneeweiss","year":"2009","journal-title":"Epidemiology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1002\/sim.8457","article-title":"Propensity score-adjusted three-component mixture model for drug-drug interaction data mining in FDA Adverse Event Reporting System","volume":"39","author":"Wang","year":"2020","journal-title":"Stat. Med."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Johara, F.T., Benedetti, A., Platt, R., Menzies, D., Viiklepp, P., Schaaf, S., and Chan, E. (2021). Evaluating the performance of propensity score matching based approaches in individual patient data meta-analysis. BMC Med. Res. Methodol., 21.","DOI":"10.1186\/s12874-021-01452-1"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3612","DOI":"10.1002\/sim.9437","article-title":"Propensity score methods for observational studies with clustered data: A review","volume":"41","author":"Chang","year":"2022","journal-title":"Stat. Med."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/12\/1028\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T13:02:19Z","timestamp":1765371739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/12\/1028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,10]]},"references-count":91,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["cimb47121028"],"URL":"https:\/\/doi.org\/10.3390\/cimb47121028","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,10]]}}}