Probing polypharmacy, ageing and sex effects on physical function using different tests

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2024-01-21 DOI:10.1111/fcp.12978

Gizem Gemikonakli, John Mach, Trang Tran, Harry Wu, Sarah N. Hilmer

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Abstract

Background

Ageing, sex and polypharmacy affect physical function.

Objectives

This mouse study investigates how ageing, sex and polypharmacy interact and affect grip strength, balance beam and wire hang, correlating and comparing the different test results between and within subgroups.

Methods

Young (2.5 months) and old (21.5 months) C57BL/6 J male and female mice (n = 10–6/group) were assessed for physical function at baseline on grip strength, balance beam and wire hang with three trials of 60 s (WH60s) and one trial of 300 s (WH300s). Mice were randomised to control or diet containing a high Drug Burden Index (DBI, total anticholinergic and sedative drug exposure) polypharmacy regimen (metoprolol, simvastatin, citalopram, oxycodone and oxybutynin at therapeutic oral doses). Following 6–8 weeks of treatment, mice were reassessed.

Results

High DBI polypharmacy and control mice both showed age group differences on all tests (p < 0.05). Only control mice showed sex differences, with females outperforming males on the WH60s and balance beam for old mice, WH300s for young mice (p < 0.05). Polypharmacy reduced grip strength in all subgroups (p < 0.05) and only in old females reduced wire hang time and cumulative behaviour and balance beam time and %walked (p < 0.05). Physical function assessments were all correlated with each other, with differences between subgroups (p < 0.05), and mice within subgroups showed interindividual variability in performance.

Conclusion

Age, sex and polypharmacy have variable effects on different tests, and behavioural measures are useful adjuvants to assessing performance. There was considerable within-group variability in change in measures over time. These findings can inform design and sample size of future studies.

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使用不同的测试探究多种药物、老龄化和性别对身体功能的影响。

背景老龄化、性别和多种药物影响身体功能：这项小鼠研究探讨了老龄化、性别和多种药物如何相互作用并影响握力、平衡木和吊线，并对亚组之间和亚组内的不同测试结果进行了关联和比较：方法：年轻（2.5 个月）和年老（21.5 个月）的 C57BL/6 J 雄性和雌性小鼠（n = 10-6/组）在基线时接受握力、平衡木和吊线的身体功能评估，其中包括三次 60 秒（WH60s）和一次 300 秒（WH300s）的测试。小鼠被随机分配到对照组或含有高药物负担指数（DBI，抗胆碱能和镇静药物总暴露量）的多药方案（治疗口服剂量的美托洛尔、辛伐他汀、西酞普兰、羟考酮和羟丁宁）的饮食中。治疗 6-8 周后，对小鼠进行重新评估：结果：高 DBI 多药小鼠和对照组小鼠在所有测试中均显示出年龄组差异（p 结论：高 DBI 多药小鼠和对照组小鼠在所有测试中均显示出年龄组差异：年龄、性别和多药性对不同测试的影响各不相同，行为测量是评估成绩的有用辅助手段。随着时间的推移，行为指标的变化在组内存在相当大的差异。这些发现可为今后研究的设计和样本大小提供参考。

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.