The Effect of Age and Frailty upon Acetanilide Clearance in Man

Wynne, Hilary; Cope, Lance; James, Ofw; Rawlins, M. D.; Woodhouse, K.W.

doi:10.1093/ageing/18.6.415

Cited by 28 publications

(12 citation statements)

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“…The risk of hospital admission secondary to a severe adverse drug reaction has been associated with increasing age and frailty, with frailty defined as comorbidity [24]. Frailty is associated with changes in pharmacokinetics and pharmacodynamics of several medications [25][26][27][28]. Increasing frailty scores on the Edmonton Frail Scale administered at a pre-admission clinic prior to elective non-cardiac surgery are associated with postoperative complications (P = 0.02), increased length of hospitalisation (P = 0.004) and inability to be discharged home (P = 0.01), independent of age [29].…”

Section: Discussionmentioning

confidence: 99%

The assessment of frailty in older people in acute care

et al. 2009

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Aim: Develop a measure of frailty for older acute inpatients to be performed by non-geriatricians. Method: The Reported Edmonton Frail Scale (REFS) was adapted from the Edmonton Frail Scale for use with Australian acute inpatients. With acute patients aged over 70 years admitted to an Australian teaching hospital, we validated REFS against the Geriatrician's Clinical Impression of Frailty (GCIF), measures of cognition, comorbidity and function, and assessed inter-rater reliability.Results: REFS was moderately correlated with GCIF (n = 105, R = 0.61, P < 0.01), Mini-Mental State Examination impairment (n = 61, R = 0.49, P < 0.001), Charlson Comorbidity Index (n = 59, R = 0.51, P < 0.001) and Katz Daily Living Scale (n = 59, R = 0.51, P < 0.001). Inter-rater reliability of REFS administered by two researchers without medical training was excellent (kappa = 0.84, n = 31). Conclusion: In this cohort of older acute inpatients, REFS is a valid, reliable test of frailty, and may be a valuable research tool to assess the impact of frailty on prognosis and response to therapy.Key words: acute care, acute illness, aged, frailty, geriatric medicine. IntroductionFrailty may affect the safety and efficacy of therapy and may be a key prognostic marker in the care of acute geriatric medicine inpatients. To test this hypothesis, a reliable, valid measure of frailty in acute inpatients is required.The core feature of frailty is increased vulnerability to stressors because of impairments in multiple inter-related systems that lead to decline in homeostatic reserve and resiliency, although the definition of frailty remains contentious [1]. Many tools for the identification of frailty, such as the phenotype model developed by Fried and colleagues [2], rely on objective measures of physical function. Purser and colleagues [3] recently described the utility of several performance-based measures and of two composite scores to identify frailty in a group of older adult inpatients with significant cardiovascular disease. However, in an acute care hospital population, performance-based measures may provide more information about the severity and type of acute illness than about the underlying frailty of a patient. The estimation of frailty just prior to acute illness in inpatients may inform decisions on management and prognosis. Self-reported function has been shown to be a good estimate of objective measures of physical function [4].Large prospective studies on the role of frailty in the prognosis of acute illness will be facilitated by the use of a frailty measure that can be performed by non-geriatrician researchers. The Edmonton Frail Scale, which is administered by a research assistant without medical training, has been validated against the Geriatricians' Clinical Impression of Frailty (GCIF) in a Canadian population referred for comprehensive geriatric assessment [5]. Interestingly, the inpatients (40% of the study population) scored significantly higher on the Edmonton Frail Scale than outpatients. While this may represent the c...

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Section: Discussionmentioning

confidence: 99%

The assessment of frailty in older people in acute care

et al. 2009

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“…Table 1 summarizes the pharmacokinetic and pharmacodynamic changes that occur with ageing and frailty. However, few studies have been conducted in older frail adults [Schwartz, 2006;Wynne et al 1993;Wynne et al 1990;Wynne et al 1989]. …”

Section: Clinical Pharmacology In Old Age and Frailtymentioning

confidence: 99%

Drug-induced liver injury in older adults

Mitchell

Hilmer

2010

Therapeutic Advances in Drug Safety

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Drug-induced liver injury (DILI) is an important cause of hospitalisation and of medication deregistration. In old age, susceptibility to DILI is affected by changes in physiology and increased interindividual variability, compounded by an increased prevalence of disease and the frailty syndrome. While dose-related or predictable DILI reactions are often detected in preclinical trials, the occurrence of rare hypersensitivity or idiosyncratic reactions cannot be reliably predicted from preclinical studies or even by clinical trials. The limited participation of older adults in clinical trials means that the susceptibility of this population to DILI is largely unknown. Vigilance during clinical trials and postmarketing surveillance must be universally practised. A systematic approach should be taken to determine not only which medicines are hepatotoxic and should be removed from the market, but also the hepatotoxicity risks from marketed drugs to consumers with different characteristics, many of whom are older people.

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“…The age-related reduction in liver size is noted to be in the order of 25 to 35%, which has been confirmed in many species including humans [9, 28–30]. The main age-related change in the physiology of the liver is a substantial reduction in blood flow of about 40% [29] which has been postulated to be due to leukocyte accumulation in the sinusoids and narrowing of sinusoidal lumens due to pseudocapillarisation and dysfunction of the liver sinusoidal endothelial cells (LSECs) [31].…”

Section: Liver Specific Changes In Ageingmentioning

confidence: 80%

Age-Related Changes in the Hepatic Pharmacology and Toxicology of Paracetamol

Mitchell

Kane

Hilmer

2011

Current Gerontology and Geriatrics Research

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Optimal pharmacotherapy is determined when the pharmacokinetics and pharmacodynamics of the drug are understood. However, the age-related changes in pharmacokinetics and pharmacodynamics, as well as the increased interindividual variation mean optimal dose selection are a challenge for prescribing in older adults. Poor understanding of how hepatic clearance and toxicity are different with age results in suboptimal dose selection, poor efficacy, and/or increased toxicity. Of particular concern is the analgesic paracetamol which has been in use for more than 50 years and is consumed by a large proportion of older adults. Paracetamol is considered to be a relatively safe drug; however, caution must be taken because of its potential for toxicity. Paracetamol-induced liver injury from accidental overdose accounts for up to 55% of cases in older adults. Better understanding of how age affects the hepatic clearance and toxicity of drugs will contribute to evidence-based prescribing for older people, leading to fewer adverse drug reactions without loss of benefit.

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The Effect of Age and Frailty upon Acetanilide Clearance in Man

Cited by 28 publications

References 0 publications

The assessment of frailty in older people in acute care

The assessment of frailty in older people in acute care

Drug-induced liver injury in older adults

Age-Related Changes in the Hepatic Pharmacology and Toxicology of Paracetamol

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