Ageing and Pharmacology Research Group

Lab head: Prof Sarah Hilmer
Location: Kolling Building, Royal North Shore Hospital

The Laboratory of Ageing and Pharmacology is part of the Penney Ageing Research Unit at the Kolling (RNSH/ Sydney University), which aims to improve healthy ageing in older people in the community and in hospital. Overall, our focus is on prevention and better management of the geriatric syndromes, including frailty, falls and confusion. 

Our laboratory’s research aims to improve the safety and efficacy of medicines for older adults. We use laboratory, clinical and population based studies to understand the risks and benefits of medicines in older people, particularly in those with multiple chronic medical conditions, multiple concurrent medications (polypharmacy) and geriatric syndromes such as frailty, falls and cognitive impairment. Our research aims to inform drug choices, doses and formulations of medicines for older people. This will help older people to benefit from medicines and will minimise adverse effects.

Our program of work on understanding and managing the effects of multiple medicines in older adults spans clinical, population and basic science studies. We developed a pharmacological risk assessment tool, the Drug Burden Index, to assess the impact of all of an older person’s medicines on their physical function. We have demonstrated that higher Drug Burden Index is associated with loss of functional independence, more falls, frailty, longer hospitalisations and greater mortality. We are now developing software, the Drug Burden Index Calculator©, which we are using to trial the Drug Burden Index in clinical practice. We are conducting several trials of deprescribing (withdrawing medicines that are likely to cause more harm than benefit) in hospitals, the community and residential aged care facilities. We have taken a novel bedside to bench approach to better understand whether and how multiple medicines impair physical and cognitive function in old age.

A major theme of our research is investigating the use and effects of medicines in frail (less resilient) older people and more recently, with the support of the NHMRC Cognitive Decline Partnership Centre, in older people with dementia. We have shown that frailty affects prescribing and use of medicines, how medicines are distributed in and cleared by the body, how medicines affect the body and their overall effectiveness and safety. Furthermore, we found that the use of multiple concurrent medicines and of particular types of medicines increases the risk of developing frailty in the future. We are currently investigating these associations in laboratory models to better understand causality and mechanism. 

In addition to studying the effects of medicines on an older person’s overall function, we also study drug induced liver disease in old age. This is one of the commonest side effects of medicines, frequently leads to medicines being withdrawn from the market, and the risk seems to increase for some but not all medicines in old age. We conduct clinical and laboratory research to understand the changing risk and mechanisms of those changes of drug induced liver disease with common drugs like the simple analgesic paracetamol and the anti-tuberculous agent, isoniazid. This research has already influenced policy and future findings should inform safe drug use for older people.

Our research group prioritises education, mentorship, capacity building and collaboration. Our research students have had backgrounds in science (pharmacology), medicine, pharmacy and nursing. Two of Professor Hilmer’s PhD graduates and one of the post-docs she mentored have been awarded NHMRC fellowships. Many others have gone on to conduct national and international post-doctoral research or to study medicine or pharmacy. Several of our early career researchers visit the laboratories of our collaborators nationally and internationally at leading research institutes such as the National Institute on Aging, NIH, USA and the Karolinska Institutet, Sweden.

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Lab members: The Ageing and Pharmacology Laboratory is led by Sarah Hilmer, who is Head of Department Clinical Pharmacology and Senior Staff Specialist Aged Care at RNSH and Conjoint Professor of Geriatric Pharmacology at Sydney Medical School. The research team currently includes 3 post-doctoral researchers, 2 PhD students, 1 Masters student, 2 Honours students, 1 registrar and 3 research assistants.
Funding: NHMRC, NSW Health, Ramsay, Penney Ageing Research Trust Fund
Research approach equipment: We conduct translational research to improve quality use of medicines in old age that includes: - basic research involving in vivo pre-clinical testing - clinical research including randomised controlled trials, observational studies, pharmacokinetic/pharmacodynamic studies - implementation research - population research with a focus on pharmaco-epidemiology - education research

Huizer-Pajkos, A., Kane, A., Howlett, S., Mach, J., Mitchell, S., De Cabo, R., Le Couteur, D., Hilmer, S. (2016). Adverse Geriatric Outcomes Secondary to Polypharmacy in a Mouse Model: The Influence of Aging. Journals of Gerontology. Series A: Biological Sciences and Medical Sciences, 72(5), 571-577.

Kane, A., Hilmer, S., Boyer, D., Gavin, K., Nines, D., Howlett, S., De Cabo, R., Mitchell, S. (2016). Impact of Longevity Interventions on a Validated Mouse Clinical Frailty Index. Journals of Gerontology. Series A: Biological Sciences and Medical Sciences, 71(3), 333-339

Nishtala, P., Gnjidic, D., Jamieson, H., Hanger, C., Kaluarachchi, C., Hilmer, S. (2016). 'Real-world' haemorrhagic rates for warfarin and dabigatran using population-level data in New Zealand. International Journal of Cardiology, 203, 746-752.

Nguyen, T., Cumming, R., Hilmer, S. (2016). Atrial fibrillation in older inpatients: are there any differences in clinical characteristics and pharmacological treatment between the frail and the non-frail? Internal Medicine Journal, 46(1), 86-95.

Scott, I., Hilmer, S., Reeve, E., Potter, K., Le Couteur, D., Rigby, D., Gnjidic, D., Del Mar, C., Roughead, E., Page, A., Jansen, J., et al (2015). Reducing inappropriate polypharmacy: the process of deprescribing. JAMA Internal Medicine, 175(5), 827-834.

Hilmer, S., Mager, D., Simonsick, E., Cao, Y., Ling, S., Windham, G., Harris, T., Hanlon, J., Rubin, S., Shorr, R., et al (2007). A drug burden index to define the functional burden of medications in older people. Archives of Internal Medicine, 167(8), 781-787

The effect of polypharmacy and deprescribing on physical and cognitive function in old age

Primary supervisor: Sarah Hilmer

Polypharmacy (concurrent use of ≥5 different medicines) is experienced by the majority of older Australians and is associated with adverse outcomes such as falls, frailty, confusion and mortality in observational studies.  Rigorous evaluation of the effects of polypharmacy and deprescribing in older adults is ethically and feasibly difficult. In this study we use our recently developed translational model of polypharmacy (Huizer-Pajkos et al., J Gerontol Biol Sci Med Sci, 2015) to evaluate whether polypharmacy causes adverse geriatric outcomes, whether these are reversible with deprescribing (withdrawal of medicines), and investigate mechanisms in a range of organs.  Depending on the skills and interests of the student, the project could involve measuring physical and/or cognitive function in mice, analysing pharmacokinetic and pharmacodynamic data, or analysing histopathologic data and performing immunohistochemical tests.  The student’s data may be publishable within a paper describing the broader project.

Discipline: Pharmacology
Co-supervisors: John Mach
Keywords: Ageing, Pharmacology, Dementia