Forensic Sci Med Pathol (2013) 9:254–255 DOI 10.1007/s12024-012-9393-3
FORENSIC FORUM
Post mortem toxicology in the elderly Roger W. Byard
Accepted: 4 November 2012 / Published online: 7 December 2012 Ó Springer Science+Business Media New York 2012
Numerous issues arise regarding drug pharmacokinetics, pharmacodynamics, and interactions in the elderly (defined as individuals aged 65 years and older). Many of the elderly suffer from progressive decline in the functional reserve of multiple organs [1], and are being treated for a multitude of chronic diseases including arthritis, hypertension, cardiovascular conditions, dementia, cancer, and diabetes [2]. Other issues that may impact upon drug levels in the elderly include factors such as nutritional status, genetic factors, and ethnicity [3]. It has been estimated that elderly patients regularly take between two and five prescription medications, with polypharmacy occurring in 20–50 % [1]. A wide variety of physiological changes occur in the elderly that may affect drug absorption, distribution, metabolism, and excretion. These include an increase in gastric pH, slower gastric emptying times, decreased splanchnic blood flow, reduced intestinal absorption area, decreased gut motility, increased body fat, reduced lean body mass and total body water, reduced serum albumin, increased a 1-acid glycoprotein, reduced liver mass and blood flow and a reduced renal blood flow and glomerular filtration rate [1]. While drug absorption from the gut may not be particularly different in the elderly, due to the competing effects of reduced absorption with slower motility, information on the absorption of slow release medications is lacking [2]. Not only does the clearance of drugs that are metabolized by the liver reduce, but the smaller liver size and decrease in hepatic blood flow may
R. W. Byard (&) Discipline of Anatomy and Pathology, Level 3 Medical School North Building, The University of Adelaide, Frome Road, Adelaide 5005, Australia e-mail:
[email protected]
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reduce first-pass metabolism and therefore give higher drug plasma concentrations. Conversely, if the active component of the drug first requires metabolic modification, then these levels may be lower [3]. Renal excretion has been shown to be reduced in two thirds of the elderly population by up to 50 % [1]. Loss of homeostatic mechanisms is another factor in the elderly that makes them less resilient to the pharmacological effects of medications and more susceptible to increases in the intensity and numbers of side effects. Examples include bleeding from anticoagulant therapy, and dehydration and electrolyte disturbances from diuretics [4]. Thus, significant underlying diseases, polypharmacy and decreased ability to metabolize and eliminate drugs and considerable inter-individual variability, all contribute to making the prescription of medications in the elderly a difficult area [5, 6]. Another issue that has been raised concerns the limited involvement of the elderly in clinical drug trials, resulting in less information being available about specific drug effects in aged individuals [7]. In addition the possibility of deliberate substance misuse should not be forgotten [8]. Given the complexity of these factors, post mortem toxicological interpretations in such individuals may be extremely complicated. A more general problem also arises in the forensic interpretation of drug levels in post mortem samples as redistribution and sample site may significantly affect levels. This is not only an issue in the elderly but in individuals at all ages [9, 10]. One issue that has not been widely considered in the elderly, however, is the effect of agonal processes on subsequent drug levels. Older people who, as was noted above, may have a number of underlying diseases requiring specific medications, including analgesics, may often be quite stable with therapeutic levels of
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these drugs. Once agonal processes begin with dehydration and renal and hepatic shutdown, however, what is the likely effect on drug levels? Is it possible that reduced plasma volume with decreased clearance and metabolic breakdown may cause an elevation in therapeutic drug levels to concentrations that may normally be regarded as toxic or even lethal in post mortem assays? Levels of comfort analgesic medication in a dying patient aimed at reducing unnecessary pain may also be spuriously elevated in the terminal stages of life. This issue will only become more significant as the aging population increases, with estimates that 20 % of the population will be older than 79 years by 2050 [1]. In a time when treatment of the elderly is being constantly scrutinized, and when high profile cases such as that involving Dr. Harold Shipman [11] emphasize the importance of evaluating the deaths of elderly individuals, post mortem drug levels may be of paramount importance. What happens, however, if they are uninterpretable?
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