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Free Content Editorial [Hot topic: The Challenge of Prescribing Drugs in Older People (Guest Editors: Fabrizia Lattanzio and Andrea Corsonello)]

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The increasing proportion of elderly people in all industrialized countries, along with improvement in medical technologies, has expanded the number of people affected by multiple chronic diseases and taking multiple drugs. As an example, about half of Medicare beneficiaries receive 5 or more medications [6]. Optimizing the treatment in the presence of many comorbid conditions is a challenging issue, and even more in the elderly because all of the factors on which the therapeutic decisions are usually based (e.g. scientific evidences, indications coming from guidelines, expected benefits, expected risks) may be of limited usefulness in this population. Indeed, elderly patients with comorbid conditions are frequently excluded from clinical trials [13]. As a result, clinical practice guidelines, that are based on the evidence coming from randomized trials and meta-analyses, can not be easily generalized to older people [11] without producing a substantial increase in the risk of drug-drug or drug-disease interactions [2]. Additionally, randomized clinical trials are usually not powered to detect safetyrelated outcomes [14], and therefore only data coming from observational studies are usually available. The incidence of adverse drug reactions (ADRs) in a community-dwelling elderly population is 50.1/1000 person-years, with significant impact on health and quality of life [5]. Overall comorbidity, the use of multiple medications for the treatment of different coexisting chronic diseases, female gender, and selected comorbid conditions (e.g. renal failure) are main determinants of high ADRs risk in older patients [3, 7-10, 15, 16]. However, agerelated changes in pharmacokinetics and pharmacodynamics could also be implicated [1, 4, 12]. The aim of this special issue was to provide to the reader a detailed picture of this truly challenging issue, in an attempt to integrate the views of pharmacologists and clinicians.

In the first paper, Shi and Klotz summarized the most recent evidence about age-related pharmacokinetic changes. A reduced bioavailability of some drugs when active transport mechanisms are involved, an increased bioavailability of some drugs undergoing extensive first-pass metabolism, an increased volume of distribution of lipophilic drugs due to age-related changes in body composition, a reduced hepatic and renal clearance, as well as the genetic influence on metabolism are all extensively described. However, it must be recognized that the interindividual variability in drug disposition is particularly prominent in the elderly probably due to several other confounding factors (e.g. frailty, comorbidity, polypharmacy, and drug interactions).

According to the paper by Trifiro and Spina, age-related changes in pharmacodynamics tend to increase the sensitivity to selected drugs, such as CNS and cardiovascular drugs, in older people. However, reduced effectiveness of conventional doses of other drugs, such as β- blockers and diuretics, was observed in elderly patients, thus supporting the idea that general rules may not be systematically applied to the effect of age-related pharmacodynamic changes. Although studies on the effect of age on drug response are generally plagued by several methodological limitations, it is worth noting that differences in drug response observed between elderly and young individuals may partly be ascribed to a decline in baseline levels of functioning with age, which means that also pharmacodynamics, and not only pharmacokinetics, may be significantly affected by frailty and comorbidity.

An example of how the importance of translating the knowledge on age-related changes in pharmacokinetics and pharmacodynamics into clinical practice is provided in the paper by De Leon. The author focuses attention on anticholinergic (or antimuscarinic) drugs. These drugs are often plagued by several central (sleep disturbances, memory deficits, cognitive deficits etc.) and peripheral (decreased sweating, blurred vision, increased heart rate, and, typically, dry mouth, constipation and urinary retention) ADRs. The paper offers and explain an exhaustive list of methods to establish the muscarinic activity of a drug, presents weakness and strength of each one, and describes factors influencing muscarinic receptor response and pharmacokinetics. The knowledge about this issue is a valuable tool for clinicians when visiting patients with absolute contraindications to antimuscarinic drugs (e.g. cognitive impairment)........
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Document Type: Research Article

Publication date: September 1, 2011

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  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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