Diurnal effects of polypharmacy with high drug burden index on physical activities over 23 h differ with age and sex.
Age Factors
Aging
Animals
Behavior, Animal
Cholinergic Antagonists
/ administration & dosage
Circadian Rhythm
Exploratory Behavior
Female
Hypnotics and Sedatives
/ administration & dosage
Locomotion
Male
Metoprolol
/ administration & dosage
Mice
Polypharmacy
Sex Factors
Simvastatin
/ administration & dosage
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 02 2022
09 02 2022
Historique:
received:
20
10
2021
accepted:
19
01
2022
entrez:
10
2
2022
pubmed:
11
2
2022
medline:
5
3
2022
Statut:
epublish
Résumé
Aging, polypharmacy (concurrent use of ≥ 5 medications), and functional impairment are global healthcare challenges. However, knowledge of the age/sex-specific effects of polypharmacy is limited, particularly on daily physical activities. Using continuous monitoring, we demonstrated how polypharmacy with high Drug Burden Index (DBI-cumulative anticholinergic/sedative exposure) affected behaviors over 23 h in male/female, young/old mice. For comparison, we also evaluated how different drug regimens (polypharmacy/monotherapy) influenced activities in young mice. We found that after 4 weeks of treatment, high DBI (HDBI) polypharmacy decreased exploration (reduced mean gait speed and climbing) during the habituation period, but increased it during other periods, particularly in old mice during the transition to inactivity. After HDBI polypharmacy, mean gait speed consistently decreased throughout the experiment. Some behavioral declines after HDBI were more marked in females than males, indicating treatment × sex interactions. Metoprolol and simvastatin monotherapies increased activities in young mice, compared to control/polypharmacy. These findings highlight that in mice, some polypharmacy-associated behavioral changes are greater in old age and females. The observed diurnal behavioral changes are analogous to drug-induced delirium and sundowning seen in older adults. Future mechanistic investigations are needed to further inform considerations of age, sex, and polypharmacy to optimize quality use of medicines.
Identifiants
pubmed: 35140291
doi: 10.1038/s41598-022-06039-4
pii: 10.1038/s41598-022-06039-4
pmc: PMC8828819
doi:
Substances chimiques
Cholinergic Antagonists
0
Hypnotics and Sedatives
0
Simvastatin
AGG2FN16EV
Metoprolol
GEB06NHM23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2168Informations de copyright
© 2022. The Author(s).
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