Individualization of drug therapy in older people (original) (raw)
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Age-Related Pharmacokinetic and Pharmacodynamic Changes and Related Risk of Adverse Drug Reactions
Current Medicinal Chemistry, 2010
Aging is known to be associated with an increased prevalence of multiple chronic diseases, which frequently causes the use of complex therapeutic regimens. The aging process is characterized by relevant changes in drug handling, physiological reserve, and pharmacodynamic response. Hepatic drug clearance of several drugs decreases with aging, mainly due to reduced blood flow, and hepatocyte mass. Renal function also declines with aging, mainly due to sclerotic changes in the glomeruli. Furthermore, due to reduced muscle mass, older subjects frequently have depressed glomerular filtration rate despite normal serum creatinine, and such a concealed renal insufficiency may impact significantly the clearance of hydrosoluble drugs. Changes in pharmacodynamics are also well documented in the cardiovascular and nervous system. Age-related changes in pharmacokinetics and pharmacodynamics, together with comorbidity and polypharmacy, make elderly patients at special risk for advers drug reactions, which in turn are cause of relevant health burden and costs. Selected measures can assist in preventing or detecting timely such adverse events.
Variability in response to medicines in older people: phenotypic and genotypic factors
Clinical pharmacology and therapeutics, 2009
Understanding the causes and consequences of variability in responses to medicines is a foundation of rational therapeutics. This relies on a detailed understanding of the pharmacokinetic and pharmacodynamic characteristics of medicines and the factors that influence them in patients. Ultimately the optimal dose regimen is determined by the pharmacological phenotype of the patient, which is a consequence of the person's genes and the environment in which they are expressed. 1 Older people display considerable variability in responses to medicines, and this makes dose selection a complex process. 2,3 Pharmacogenomic factors play some part in this variability, but other clinical factors also determine an older person's phenotypic response to a medicine. In this article we conclude that with older age, genotype plays an increasingly small role in determining a person's phenotypic response to a medicine.
The Risk of Adverse Drug Reactions in Older Patients: Beyond Drug Metabolism
Current Drug Metabolism, 2011
Changes in pharmacokinetics and pharmacodynamics, associated with increasing age, are often considered the only culprits of increasing Adverse Drug Reactions (ADR) rate observed in older adults, but other factors may be responsible for a reduction in drug efficacy and increase the risk of iatrogenic illness in this population. The aging process is characterized by a high level of complexity, which makes the care of older adults and the use of medications a challenging task. In particular, comorbidity, geriatric syndromes, cognitive and functional deficits, limited life expectancy are typical conditions observed in older adults which may reduce the efficacy of prescribed drugs and increase the risk of iatrogenic illness. As a consequence, a comprehensive assessment and management of the health care problems, with the goal of recognizing and preventing potential drug-related problems and improve quality of prescribing is necessary to reduce the risk of ADR. Several studies have assessed the effect of a comprehensive geriatric assessment and management on drug prescribing and drug related illness, showing a substantial improvement in quality of prescription and a reduction in rate of ADR. In addition, clinical guidelines providing recommendations regarding the use of drugs in chronic disease rarely assess the level of complexity observed in older adults and therefore they should be applied with caution in this population.
British Journal of Clinical Pharmacology, 2019
Ageing is associated with several changes in human organs, which result in altered medication pharmacokinetics and pharmacodynamics. Ageing is also associated with changes in human body functions, such as impaired vision, hearing, swallowing, motor and cognitive functions, which can affect the adequate intake and administration of drugs. As a consequence, older people, and especially patients older than 75 years, are the main users of many drugs and they frequently use 5 drugs or more long-term (i.e. polypharmacy). All this increases the complexity of adequate drug intake, administration and adherence. However, there is a lack of evidence on the considerations that should be taken into account to ensure appropriate drug prescribing to older people. This review article summarizes the most clinically relevant changes in human organ and body functions and the consequential changes in pharmacokinetics and pharmacodynamics in older people, along with possible dosing consequences or alternatives for drugs frequently prescribed to this patient population. Recommendations are given on how ageing could be considered in clinical drug development, drug authorization and appropriate prescribing.
Current strategies to streamline pharmacotherapy for older adults
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2018
Although the term "personalized medicine" has been associated in many cases with pharmacogenomics, its definition embraces the use of specific biomarkers and covariates to help in the selection of medical treatments and procedures which are best for each patient. While several efforts have been performed for the tailored selection of therapies and dosing regimens in the general population, developing personalized medicine initiatives for elderly patients remains understudied. The personalized drug therapy for older patients requires the consideration of anatomical, physiological and functional alterations in a multimorbid setting requiring multiple medications. The present review focuses on currently employed qualitative and quantitative precision medicine approaches for elderly patients and discusses some of the associated challenges and limitations. Furthermore, the use of and confidence in physiologically-based approaches for optimal dose selection in this understudied ...
Australian family physician, 2004
Prescribing medications to older people is difficult due to comorbidity, limited evidence for efficacy, increased risk of adverse drug reactions, polypharmacy, and altered pharmacokinetics. This article describes the principles underlying clinical geriatric pharmacology including approaches to evaluating the evidence for risk and benefit, and adjusting dose for age related pharmacokinetic changes. The challenge for the general practitioner is to balance an incomplete evidence base for efficacy in frail, older people against the problems related to adverse drug reactions without denying older people potentially valuable pharmacotherapeutic interventions.
Pharmaceutica Analytica Acta, 2011
The combination of drugs may be a result of a necessary therapeutic strategy against a single disease or a fortuitous treatment of two or more health disorders. In either case, a consequence of such approach is the increased risk of drug interactions and subsequent adverse effects. For the elderly, the probability of these events is significantly increased compared to other age groups, not only because of combining medications but also agerelated pharmacokinetic (absorption, distribution, biotransformation and excretion processes) alteration. Since the growth rate of the elderly population worldwide is rapidly increasing, clinicians should be extremely cautious of the drugs prescribed to older patients in order to minimize drug interactions and therapeutic failure.
Drug metabolism in older peoplea key consideration in achieving optimal outcomes with medicines
The Journals …, 2011
Hepatic clearance plays a key role in determining the systemic exposure of drugs and metabolites, which in turn has a major effect on variability in the beneficial and adverse effects of medicines. Aging results in a number of significant changes in the human liver including reductions in liver blood flow, size, drug-metabolizing enzyme content, and pseudocapillarization. Drug metabolism is also influenced by comorbid disease, frailty, concomitant medicines, and (epi) genetics. These changes have the potential to alter the hepatic clearance of drugs but need to be interpreted in the context of the pharmacokinetic (and pharmacodynamic) characteristics of the drug of interest. There is growing evidence that the age-related changes in the liver not only result in a decrease in the hepatic clearance of unbound drug but also influence variability in response to medicines in older people.