Aging Biology and Geriatric Clinical Pharmacology

McLean, Allan J.; Couteur, David G. Le

doi:10.1124/pr.56.2.4

Cited by 662 publications

(507 citation statements)

References 280 publications

(298 reference statements)

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“…Reduced hepatic blood flow in the elderly has been suggested to be the major effect of aging on the liver circulation (McLean and LeCouteur, 2004;Wynne et al, 1989). Only a few studies have reported age-related structural and functional changes in the hepatic microvasculature.…”

Section: Age-related Changes In Liver Microcirculation In Micementioning

confidence: 99%

“…Aging of the liver is associated with reduction in its mass as well as a 30-40% reduction in blood flow (McLean and LeCouteur, 2004;Wynne et al, 1989). These changes are accompanied by impaired metabolism that have potential clinical implications including adverse drug reactions, susceptibility to toxins, and atherosclerosis due to spill-over of atherogenic molecules into the systemic circulation Schmucker, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Age-related changes in the hepatic microcirculation in mice

Yoshiya

Sørensen

Bethea

et al. 2007

Experimental Gerontology

113

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Aging of the liver is associated with impaired metabolism of drugs, adverse drug interactions, and susceptibility to toxins. Since reduced hepatic blood flow is suspected to contribute this impairment, we examined age-related alterations in hepatic microcirculation.. Livers of C57Bl/6 mice were examined at 0.8 (pre-pubertal), 3 (young adult), 14 (middle-aged) and 27 (senescent) months of age using in vivo and electron microscopic methods. The results demonstrated a 14% reduction in the numbers of perfused sinusoids between 0.8 and 27 month mice associated with 35% reduction in sinusoidal blood flow. This was accompanied by an inflammatory response evidenced by a 5-fold increase in leukocyte adhesion in 27 month mice, up-regulated expression of ICAM-1, and increases in intrahepatic macrophages. Sinusoidal diameter decreased 6-10%. Liver sinusoidal endothelial cell (LSEC) dysfunction was seen as early as 14 months when there was a 3-fold increase in the numbers of swollen LSEC. The endocytotic capacity of LSEC also was found to be reduced in older animals. The sinusoidal endothelium in 27 month old mice exhibited pseudocapillarization. In conclusion, the results suggest that leukocyte accumulation in the sinusoids and narrowing of sinusoidal lumens due to pseudocapillarization and dysfunction of LSEC reduce sinusoidal blood flow in aged livers.

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Section: Age-related Changes In Liver Microcirculation In Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Age-related changes in the hepatic microcirculation in mice

Yoshiya

Sørensen

Bethea

et al. 2007

Experimental Gerontology

113

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“…Age‐related pharmacokinetic changes occur in all older people,20, 21, 22 and an altered blood‐brain permeability in people with dementia means that they may be more sensitive to neurological and cognitive effects of medications than their peers 23, 24. These pharmacokinetic changes are additional to drug‐disease interactions that occur in dementia 25.…”

Section: Introductionmentioning

confidence: 99%

Medication appropriateness tool for co‐morbid health conditions in dementia: consensus recommendations from a multidisciplinary expert panel

Page

Potter

Clifford

et al. 2016

Internal Medicine Journal

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BackgroundMedication management for people living with dementia is a complex task as it is unclear what constitutes optimal medication management in this population due to the shifting focus of health priorities and the balance between the benefits and harms of medications.AimThis study sought expert opinion to create a consensus list to define appropriate medication management of co‐morbidities for people with dementia.MethodsThis study used the Delphi technique. We invited multidisciplinary experts in geriatric therapeutics including pharmacists, doctors, nurse practitioners, a patient advocate and a psychologist to participate. Participants were asked to engage into three or more rounds of questioning. Round 1 was a questionnaire comprised of one question defining dementia and seven open‐ended questions about appropriate management of co‐morbidities in people with dementia. Two investigators qualitatively analysed the responses to questions from Round 1 using thematic analysis. The results of this analysis were provided to participants as statements in the Round 2 survey. The participants were asked to rate their agreement with each statement on a 5‐point Likert scale. The median and interquartile range (IQR) were calculated for the responses to each statement. Consensus was pre‐specified as an IQR less than or equal to 1. Statements where consensus was not achieved were presented to participants in Round 3. The Round 2 median and IQR values were provided and participants were again asked to rate their agreement with each statement on a 5‐point Likert scale. The statements where participants agreed or strongly agreed were included in the Medication Appropriateness Tool for Co‐morbid Health conditions in Dementia criteria.ResultsFifty‐seven experts agreed to participate in the study, of whom 58% were pharmacists and 36% were medical practitioners. Fifty‐five participants completed the Round 1 (95% response rate). A total of 128 statements was included in the Round 2 survey. Consensus was reached on 93 statements in Round 2 (n = 48 responders, 84% response rate) and on 18 statements in Round 3 (n = 43 responders, 75% response rate). The participants reached consensus on 111 of 128 statements. Of these statements, 67 statements were included in the Medication Appropriateness Tool for Co‐morbid Health conditions in Dementia criteria. The statements were in the broad themes of preventative medication, symptom management, disease progression, psychoactive medication, treatment goals, principles of medication use, side‐effects and medication reviews.DiscussionThis research provides consensus‐based guidance for clinicians who manage co‐morbid health conditions in people with dementia.

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“…Treatment of the elderly patient population is influenced by the presence of comorbid illness, concomitant use of medications, functional status, and vital organ functions (hepatic, renal, and bone marrow). 4 Elderly patients are often treated with suboptimal regimens because of misconceptions among oncologists and patients of the risk-benefit ratio of chemotherapy. Furthermore, elderly patients are underrepresented in clinical trials, 5 thus making it difficult to extrapolate treatment data to the population at large.…”

mentioning

confidence: 99%

Comparison of outcomes for elderly patients treated with weekly paclitaxel in combination with carboplatin versus the standard 3‐weekly paclitaxel and carboplatin for advanced nonsmall cell lung cancer

Ramalingam

Perry

Rocca

et al. 2008

Cancer

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BACKGROUND.The purpose of this study was to compare the outcomes between elderly (aged ≥70 years) patients treated with paclitaxel on a weekly basis and with carboplatin (every 4 weeks) versus the standard 3‐weekly regimen of carboplatin and paclitaxel for first‐line therapy of advanced nonsmall cell lung cancer.METHODS.Of the 444 patients enrolled, 136 (31%) were aged ≥70 years. Seventy‐two patients were randomized to the weekly schedule (paclitaxel, 100 mg/m2 weekly for 3 of 4 weeks; carboplatin, area under the curve [AUC] = 6 mg/mL·min on Day 1 every 4 weeks), and 64 patients were randomized to the standard schedule (paclitaxel, 225 mg/m2; carboplatin, AUC = 6 mg/mL·min on Day 1 every 21 days). Patients with stable disease or objective response after 4 cycles of therapy were eligible for maintenance therapy with weekly paclitaxel (70 mg/m2, 3 of 4 weeks).RESULTS.The response rate for elderly patients was 26% on the weekly regimen and 19% on the standard schedule. The median survival duration for the weekly and the standard schedules was 37 weeks and 31 weeks, respectively. The 1‐year survival rates were similar at 31% and 33%. Grade 3 to 4 anemia was more common on the weekly schedule (16% vs 6%), whereas grade 3 neuropathy was less common (5.5% vs 9.5%). Nausea and emesis were also less frequent on the weekly schedule.CONCLUSIONS.Efficacy was similar between the weekly regimen and the standard regimen of carboplatin and paclitaxel for elderly patients with advanced NSCLC and may be advantageous based on its favorable tolerability profile. Cancer 2008. © 2008 American Cancer Society.

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Aging Biology and Geriatric Clinical Pharmacology

Cited by 662 publications

References 280 publications

Age-related changes in the hepatic microcirculation in mice

Age-related changes in the hepatic microcirculation in mice

Medication appropriateness tool for co‐morbid health conditions in dementia: consensus recommendations from a multidisciplinary expert panel

Comparison of outcomes for elderly patients treated with weekly paclitaxel in combination with carboplatin versus the standard 3‐weekly paclitaxel and carboplatin for advanced nonsmall cell lung cancer

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