Pharmacokinetic and pharmacodynamic alterations in older people with dementia

Abstract

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.

Deprescribing cholinesterase inhibitors and memantine in dementia: guideline summary

“…People with dementia may be at a greater risk of adverse drug reactions than those without dementia, and such reactions may go unrecognised, leading to prescribing cascades (for example, urinary incontinence may lead to prescribing an anticholinergic drug to treat this symptom) . In fact, ChEIs and memantine may be the greatest contributors to adverse drug reactions in people with dementia …”

“…If clinicians and family or carers notice a sustained or accelerated decline in multiple areas such as cognition, function and behaviour, this may indicate that the medication is no longer of benefit. There is also potential for harm and burden, especially in an individual who is frail, multimorbid and/or taking multiple medications This highlights the need for regular reassessment and discussion with carers and families, balancing any benefits (or lack thereof) and potential for harm in the context of the individual's care goals.…”

Pharmacist-led intervention to improve medication use in older inpatients using the Drug Burden Index: a study protocol for a before/after intervention with a retrospective control group and multiple case analysis

“…Frailty is a condition of cumulative reduction in function of multiple body systems 12. Frail individuals are vulnerable to external stressors and less able to recover; as such, they are at greater risk of medication related harms 13. Despite the knowledge of the risks associated with anticholinergic and sedative medications, their use is relatively common with studies showing use of one or more of these agents in approximately 20%–80% of older adults 8.…”

“…Despite the knowledge of the risks associated with anticholinergic and sedative medications, their use is relatively common with studies showing use of one or more of these agents in approximately 20%–80% of older adults 8. Concerningly, their use may also be more common in frail older adults who are at further risk of harm from medication use 13 14…”

Development and pilot testing of the revised Patients’ Attitudes Towards Deprescribing questionnaire for people with cognitive impairment

“…In addition to appropriate prescribing of new medications, regular assessment of the continuing need of a medication as well as its potential for harm is required, that is identification and deprescription of inappropriate medications . Deprescribing is complex in people with dementia due to limited evidence on the benefits/harms and pharmacokinetics/pharmacodynamics of medications in this population, difficulties establishing goals of care and the involvement of family members/carers in decision‐making .…”