Drug metabolism in the elderly: A multifactorial problem?

Abstract

Whether or not an individual's drug metabolising capacity declines with advancing age is a vexing question. There is no clear evidence that drug metabolism itself ('the biologically-assisted chemical alteration of the administered parent molecule') is less efficient in healthy old age than at younger ages, whereas a decreased capacity may be associated with ill-health and frailty. However, elderly individuals do show a reduced enzyme induction capability and are less able to tolerate overdoses. It appears that the majority of deleterious clinical outcomes related to drug therapy in an elderly (usually ill or frail) population may be ascribed to various anatomical and physiological age-related changes. These may affect both pharmacodynamics and pharmacokinetics, but not necessarily drug metabolism. Information gleaned from animal studies undertaken mainly in rodents does not seem to be of relevance to humans and studies in healthy aged human populations may not highlight possible problems. However, certain circumstances may influence metabolic competence, and phenotyping rather than genotyping is of more value in identifying those susceptible to adverse drug reactions. This short review discusses the potential contributions of four factors (inflammation, circadian rhythm, gut microbes, epigenetic aspects) which may lead to alterations in drug metabolism with increasing age.

Elderly and Polypharmacy: Physiological and Cognitive Changes

“…Also, external factors such as exposure to environmental contaminants are responsible for altering gene expression. These changes reflect the differential biological ageing [5].…”

“…drugs. Frailty is associated with higher inflammatory markers and a reduction in the activity of esterases (enzymes class that catalyse hydrolysis reactions) [5].…”

“…Through the normal ageing process, changes occur with impact on the pharmacodynamics and pharmacokinetics of drugs. These changes may be related to the function of particular organs, homeostatic mechanisms and also to the ability to respond to specific receptors, causing greater vulnerability and susceptibility to ADR in older patients [5] frequently associated with the use of potentially inappropriate medication (PIM) in this population [6]. The inappropriate prescription in older patients occurs when the risk of adverse effects exceeds the clinical benefit, especially when there are more effective alternatives available [7].…”

Metastasiertes Nierenzellkarzinom: Ist das Alter therapierelevant?

“…Mehrfacherkrankungen treten in dieser Gruppe besonders häufig auf. Hinzu kommen mögliche Veränderungen im Medikamentenmetabolismus und reduzierte körperliche Reserven [4, 5]. All dies kann die Therapieverträglichkeit und den -verlauf beeinflussen.…”

Operacionalização para Portugal da Lista EU(7)-PIM para Identificação de Medicamentos Potencialmente Inapropriados nos Idosos

“…[7][8][9][10][11][12] Com as alterações fisiológicas que ocorrem com o envelhecimento, a farmacocinética e farmacodinâmica de muitos fármacos está alterada nos idosos, modificando a resposta farmacológica esperada para alguns medicamentos. [13][14][15][16] Estas alterações, associadas à presença de comorbilidades e polimedicação, tornam a população idosa mais suscetível à ocorrência de reações adversas aos medicamentos, com relevante impacto na saúde e no bem-estar. 13,17 O uso inadequado de medicamentos em idosos que sofrem de múltiplas doenças constitui um problema de saúde pública devido ao seu impacto na morbilidade, na qualidade de vida e no uso acrescido de recursos de saúde.…”