Age-Related Changes in Hepatic Function: An Update on Implications for Drug Therapy

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.

Medication use in older patients and age-blind approach: narrative literature review (insufficient evidence on the efficacy and safety of drugs in older age, frequent use of PIMs and polypharmacy, and underuse of highly beneficial nonpharmacological strategies)

“…It is known that older people respond differently to drug therapies and the risk of adverse drug events (e.g., drug interactions, adverse drug reactions, and other complications) is higher in this population due to age-related changes in pharmacokinetics and pharmacodynamics (for a comprehensive overview of pharmacological changes, see Table 1 [11][12][13]) and also due to frailty, higher degree of comorbidity, polypharmacy, and other risk factors [2][3][4]14]. Up until now, controlled clinical trials have largely focused on the assessment of single treatment strategies or strategies applying maximally 2-3 drugs simultaneously, and mostly on non-geriatric subjects and/or subjects without multiple comorbid conditions.…”

Association between using medications with anticholinergic properties and short‐term cognitive decline among older men: A retrospective cohort study in Taiwan

“…The use of anticholinergic drugs has been strongly associated with adverse health outcomes, including cognitive impairment, dementia, falls, functional decline, hospitalization and mortality, especially in older adults . With advanced aging, people can become more susceptible to anticholinergic adverse effects as a result of: (i) the decreased level of acetylcholine synthesis or the decreased number of acetylcholine receptors, leading to increased pharmacodynamics sensitivity; (ii) the reduction in hepatic metabolism and renal excretion and (iii) higher blood–brain barrier permeability, allowing more anticholinergic drugs crossing into the brain . Therefore, the American Geriatrics Society Beers criteria constantly recommended avoid using medications with anticholinergic effects for older people…”

The Role of Pharmacists in Preventing Falls among America’s Older Adults

“…Although MTM is a relatively new term, pharmacists have always been involved in medication review and management, despite their practice sites. A thorough medication review by a pharmacist includes a review of age-related physical changes that predispose older adults to drug–drug interactions, drug–disease interactions, and medication side effects that can increase the patient’s chances of falling (4, 23–25). For example, with age, the kidneys and liver may become less efficient, and the distribution of water and fat within the body changes.…”

“…These physiological changes may affect the patient’s ability to metabolize medications, leading to exposure to higher doses, and an increased risk of adverse events. With every review, clinical pharmacists evaluate renal and hepatic functions to account for acute changes, modifying dose and/or frequency as needed (25, 26). In managing therapy, they consider health priorities and patient concerns, but always put patient safety and injury prevention as a priority.…”