Pharmacokinetic and pharmacodynamic alterations in older people with dementia

ABSTRACT

Introduction: The number of people with dementia internationally is increasing. Older adults with dementia are prescribed multiple medications, both to treat dementia symptoms and to manage their other medical conditions. Dementia is correlated with increasing age and frailty; this provides insight into how the efficacy and toxicity of medications may be altered in people with dementia.

Areas covered: This review discusses the current evidence of the alterations in pharmacokinetics that can occur with aging, frailty and in people with dementia. The evidence is presented via the four primary pharmacokinetic processes (absorption, distribution, metabolism and elimination). Additionally, distribution into the brain, sex considerations and potential pharmacodynamic alterations in older people with dementia are discussed.

Expert opinion: While the evidence is limited, people with dementia appear to be at a higher risk of toxicity of some medications due to altered pharmacokinetic processes and pharmacodynamics. There are a number of limitations to the research and there are still significant gaps in knowledge in this field. Proactive, ongoing review of the appropriateness of choice of medication, dose and whether or not a medication is required at all is necessary for achieving quality use of medications in people living with dementia.

KEYWORDS:

• Blood brain barrier
• dementia
• frailty
• older adults
• pharmacodynamics
• pharmacokinetics

Article highlights

• Little research was identified which specifically studied changes in pharmacokinetics in people with dementia compared to those without. However, knowledge of the alterations that occur with aging and frailty can help inform using medications safely and effectively in this population.

• Several physiological changes were identified which may alter the pharmacokinetics of medications (additional to those associated with aging). People with dementia have an increased risk of weight loss as well as reduced albumin and possible reduced alpha 1-acid glycoprotein which can alter the volume of distribution of drugs. Reduced renal function is also common in this population.

• People with dementia (specifically Alzheimer’s disease and vascular dementia) have increased permeability of their blood brain barrier and reduced P-glycoprotein activity. These changes may lead to increased access of drugs to the brain and be responsible for the increased risk of adverse drug reactions in this population.

• Pharmacodynamically, reduced acetylcholine in the brain (observed in people with dementia) increases susceptibility to adverse cognitive side effects of anticholinergics.

• Clinicians should monitor for both benefits and harms of medication use, not just following initiation of therapy but throughout treatment. Dementia is, in general, a progressive disease. As a person ages, their body composition, liver and renal function, co-morbidities and medications will change. Additionally, as the severity of the dementia increases the goals of treatment will change. Therefore, the efficacy, necessity and toxicity of medications may change in an individual over time.

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Declaration of interest

Emily Reeve is supported by an NHMRC-ARC Dementia Research Development Fellowship. Kenneth Rockwood founded and has shares in DGI Clinical, a company that has contracts with pharma for individualized outcome measurement and advanced data analytics in Alzheimer disease, Parkinson disease and other disorders. Shanna Trenaman is supported by the Canadian Consortium on Neurodegeneration in Aging (CCNA). The CCNA receives funding from the Canadian Institutes of Health Research (CAN-137794) and partner organizations). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.