Emerging drug therapies for frailty

Christopher A. Jeffery, David W.C. Shum, Ruth E. Hubbard

The metaphor of a frail older person as a car running out of petrol seems to have resonance in the lay media. Though it may be an over simplistic representation of a complex and dynamic process, it does facilitate discussion with patients and their relatives about the appropriateness of interventions, such as whether or not there is enough fuel (physiological reserves) to get up a really steep hill (undergo a coronary bypass graft). It can also be used as a way to emphasise what can be done to help. For example, in some longitudinal studies, 5% of older patients are less frail after 5 years follow up, suggesting there are things that can still be done to "fill up the tank". This review will consider whether drug therapies can fulfil this role. Frail older people are often prescribed long lists of medications but it is debatable whether current treatments actually address the causes or consequences of frailty itself. Here, we explore the associations between frailty and co-morbidity and evaluate whether the management of chronic disease may impact frailty development or progression. We consider how the management of hypertension may have an important role in the prevention of frailty, mediated by reduction of cerebrovascular disease, but why aggressive management of hypertension may have negative consequences for those who are already frail. We also summarise the evidence linking immunosenescence, inflammation and endocrine changes to frailty and investigate whether targeted drug therapy has the potential to influence frailty pathophysiology.