Age-Associated General Pharmacological Aspects
Pharmacokinetics describes the path of a drug in the body; its major constituents are
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Pharmacokinetics Pharmacokinetics describes the path of a drug in the body; its major constituents are – Absorption – Distribution – Metabolism and – Elimination (ADME rule) The result of these subfunctions of pharmacokinetics is the course of the plasma (or cerebrospinal fluid [CSF]) concentration of a drug over time. Dose, dosage form, and administration route can be chosen; all other parameters are variably determined by the individual patient, and their impact is often difficult to predict. Utilizing the development of often-complex mathematical models, pharmacokinetics attempts to describe drug concentrations over time reproducibly with a high predictability. Yet, a reliable prediction of adverse drug reactions (ADRs) cannot be achieved even by the molecular analysis of, for example, degrading enzymes as the variation of plasma drug concentrations is genetically determined only by 30–50%. Therefore, despite all attempts to forecast outcomes (e.g., via genetic testing), any drug application remains an individual experiment
M. Wehling (*) University of Heidelberg, Maybachstr. 14, Mannheim 68169, Germany e-mail: [email protected]
that can only be successfully done on close observation (of the patient). This means that despite the extensive knowledge of pharmacokinetics and pharmacogenetics, each drug application to humans represents an individual experiment that will only be meritorious if both wanted and unwanted effects are intensively searched for. This especially applies to elderly patients as they have altered functions of many organs, which are detailed here. The combination of drug concentration determinations and careful clinical observation will contribute to the increased safety of drug therapy. This includes history taking of typical side effects, such as muscle pain under statins or epigastric pain under nonsteroidal anti-inflammatory drugs (NSAIDs). However, this is an arduous and time-consuming task without a true alternative as many modern drugs (especially those with narrow therapeutic ranges) are like sharp knives: You need to learn how to use them, or they may cause more harm than good.
Special Aspects of Geriatric Pharmacokinetics Physiological Alterations, with the Kidneys in Focus Age-associated physiological alterations vary considerably between individuals. In addition, many chronic diseases are age dependent (such as Alzheimer’s dementia, atherosclerotic disease in various vascular beds) and lead to an increasing
M. Wehling (ed.), Drug Therapy for the Elderly, DOI 10.1007/978-3-7091-0912-0_3, # Springer-Verlag Wien 2013
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incidence of structural and functional deviations. These often directly contribute to incapacities and disabilities with direct impact on pharmacokinetics. Thus, it is often impossible to separate age-related alterations from those that depend on diseases with increasing incidence at higher age (such as diabetes mellitus type 2). As an example, there is a well-known decrease of glomerular function with age, reflecting a decreasing number o
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