Adverse Geriatric Outcomes Secondary to Polypharmacy in a Mouse Model: The Influence of Aging.
We aimed to develop a mouse model of polypharmacy, primarily to establish whether short-term exposure to polypharmacy causes adverse geriatric outcomes. We also investigated whether old age increased susceptibility to any adverse geriatric outcomes of polypharmacy. Young (n= 10) and old (n= 21) male C57BL/6 mice were administered control diet or polypharmacy diet containing therapeutic doses of five commonly used medicines (simvastatin, metoprolol, omeprazole, acetaminophen, and citalopram). Mice were assessed before and after the 2- to 4-week intervention. Over the intervention period, we observed no mortality and no change in food intake, body weight, or serum biochemistry in any age or treatment group. In old mice, polypharmacy caused significant declines in locomotor activity (pre minus postintervention values in control 2 ± 13 counts, polypharmacy 32 ± 7 counts,p< .05) and front paw wire holding impulse (control -2.45 ± 1.02 N s, polypharmacy +1.99 ± 1.19 N s,p< .05), loss of improvement in rotarod latency (control -59 ± 11 s, polypharmacy -1.7 ± 17 s,p< .05), and lowered blood pressure (control -0.2 ± 3 mmHg, polypharmacy 11 ± 4 mmHg,p< .05). In young mice, changes in outcomes over the intervention period did not differ between control and polypharmacy groups. This novel model of polypharmacy is feasible. Even short-term polypharmacy impairs mobility, balance, and strength in old male mice.
Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital and Kolling Institute of Medical Research, St Leonards, NSW, Australia.
Aniko
A
Huizer-Pajkos
Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital and Kolling Institute of Medical Research, St Leonards, NSW, Australia. Sydney Medical School, University of Sydney, NSW, Australia.
Alice E
AE
Kane
Departments of Pharmacology and Medicine (Geriatric Medicine), Dalhousie University, Halifax, Nova Scotia, Canada.
Susan E
SE
Howlett
Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital and Kolling Institute of Medical Research, St Leonards, NSW, Australia. Sydney Medical School, University of Sydney, NSW, Australia.
John
J
Mach
Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
Sarah J
SJ
Mitchell
Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
Rafael
R
de Cabo
Sydney Medical School, University of Sydney, NSW, Australia. Ageing and Alzheimer's Institute, Concord Hospital, Concord, NSW, Australia.
David G
DG
Le Couteur
Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital and Kolling Institute of Medical Research, St Leonards, NSW, Australia. Sydney Medical School, University of Sydney, NSW, Australia. sarah.hilmer@sydney.edu.au.
Sarah N
SN
Hilmer
D000375:Aging; D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D053580:Muscle Strength; D019338:Polypharmacy; D004856:Postural Balance; D011930:Reaction Time