Age-related changes in hepatic function: an update on implications for drug therapy

Tan, Joseph L., Eastment, Jacques G., Poudel, Arjun and Hubbard, Ruth E. (2015) Age-related changes in hepatic function: an update on implications for drug therapy. Drugs and Aging, 32 12: 999-1008. doi:10.1007/s40266-015-0318-1


Author Tan, Joseph L.
Eastment, Jacques G.
Poudel, Arjun
Hubbard, Ruth E.
Title Age-related changes in hepatic function: an update on implications for drug therapy
Journal name Drugs and Aging   Check publisher's open access policy
ISSN 1179-1969
1170-229X
Publication date 2015-11-07
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1007/s40266-015-0318-1
Open Access Status Not Open Access
Volume 32
Issue 12
Start page 999
End page 1008
Total pages 10
Place of publication Auckland, New Zealand
Publisher Springer International Publishing
Collection year 2016
Language eng
Abstract The accumulation of deficits with increasing age results in a decline in the functional capacity of multiple organs and systems. These changes can have a significant influence on the pharmacokinetics and pharmacodynamics of prescribed drugs. Although alterations in body composition and worsening renal clearance are important considerations, for most drugs the liver has the greatest effect on metabolism. Age-related change in hepatic function thereby causes much of the variability in older people’s responses to medication. In this review, we propose that a decline in the ability of the liver to inactivate toxins may contribute to a proinflammatory state in which frailty can develop. Since inflammation also downregulates drug metabolism, medication prescribed to frail older people in accordance with disease-specific guidelines may undergo reduced systemic clearance, leading to adverse drug reactions, further functional decline and increasing polypharmacy, exacerbating rather than ameliorating frailty status. We also describe how increasing chronological age and frailty status impact liver size, blood flow and protein binding and enzymes of drug metabolism. This is used to contextualise our discussion of appropriate prescribing practices. For example, while the general axiom of ‘start low, go slow’ should underpin the initiation of medication (titrating to a defined therapeutic goal), it is important to consider whether drug clearance is flow or capacity-limited. By summarising the effect of age-related changes in hepatic function on medications commonly used in older people, we aim to provide a guide that will have high clinical utility for practising geriatricians.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Centre for Research in Geriatric Medicine Publications
Official 2016 Collection
School of Medicine Publications
School of Pharmacy Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 1 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 24 Nov 2015, 00:27:02 EST by System User on behalf of Scholarly Communication and Digitisation Service