Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore, there may be a failure to maintain homeostasis under conditions of physiological stress. The reduced homeostatic ability affects different regulatory systems in different subjects, thus explaining at least partly the increased interindividual variability occurring as people get older. Important pharmacokinetic and pharmacodynamic changes occur with advancing age. Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life) whereas pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs. This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.

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Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

Sufficient quantities of water for household use, including for drinking, food preparation and hygiene, are needed to protect public health and for well-being and prosperity.



This second edition reviews the evidence about the relationships between water quantity, water accessibility and health. The effects of water reliability, continuity and price on water use, are also covered. Updated guidance, including recommended targets, is provided on domestic water supply to ensure beneficial health outcomes.

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Domestic water quantity, service level and health

Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients

This review examines the current knowledge of water intake as it pertains to human health, including overall patterns of intake and some factors linked with intake, the complex mechanisms behind water homeostasis, and the effects of variation in water intake on health and energy intake, weight, and human performance and functioning. Water represents a critical nutrient, the absence of which will be lethal within days. Water's importance for the prevention of nutrition-related noncommunicable diseases has received more attention recently because of the shift toward consumption of large proportions of fluids as caloric beverages. Despite this focus, there are major gaps in knowledge related to the measurement of total fluid intake and hydration status at the population level; there are also few longer-term systematic interventions and no published randomized, controlled longer-term trials. This review provides suggestions for ways to examine water requirements and encourages more dialogue on this important topic.

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Water, hydration, and health.

Excess hospital admissions during the July 1995 heat wave in Chicago

To determine whether responses to dehydration are altered with age, we investigated the thirst, fluid and electrolyte responses, and hormonal responses to 24 hours of water deprivation in seven healthy active elderly men (67 to 75 years old) and seven healthy young men (20 to 31 years old) who were matched for weight loss during water deprivation. After water deprivation, the older men had greater increases in plasma osmolality, sodium concentration, and vasopressin levels. However, their urinary osmolality was lower and they were less thirsty and drank less after water deprivation, so that their plasma and urine were not diluted to predeprivation levels. Regression analysis indicated increased sensitivity of vasopressin osmoreceptors in the older group, although this difference was not statistically significant. We conclude that after 24 hours of water deprivation, there is a deficit in thirst and water intake in healthy elderly men, as compared with younger men, although vasopressin osmoreceptor responsiveness is maintained or even increased. Our findings also suggest that the well-known deficit in urinary concentrating ability that occurs with age reflects renal causes and not a lack of circulating vasopressin.

Reduced Thirst after Water Deprivation in Healthy Elderly Men

The renal and vasopressin (AVP) response to a standard oral water load (20 ml/kg) was examined in a group of water-replete healthy elderly men (n = 6). Two groups, respectively, of water-replete and water-deprived young healthy volunteers acted as controls. After 2 h, the old group had excreted 41 +/- 2.4% (mean +/- SEM) of the water load compared to 100.7 +/- 8.8% in the water-replete young group and 70 +/- 3.8% in the water-deprived young group (P less than 0.01). Similarly, peak diuresis (7.01 +/- 0.48 ml/kg) and peak free-water clearance (5.7 +/- 0.48 ml/min) as determined from hourly sampling in the old group were delayed and significantly less than both young groups (P less than 0.01) (peak diuresis, young water-replete, 10.86 +/- 0.56 ml/kg, young water-deprived, 10.2 +/- 0.64 ml/kg, peak free-water clearance, young water-replete 8.4 +/- 0.72 ml/min, young water-deprived 9.5 +/- 0.88 ml/min). When these indices were adjusted for reduced creatinine clearance (Ccr) in the elderly, there was no significant difference between the young and old groups. Plasma AVP decreased similarly in all three groups following ingestion of water but there was no significant difference in mean plasma AVP between the young and old subjects throughout the study period. We therefore conclude that ability to excrete excess water promptly is impaired in healthy elderly men. This defect is due, at least in part, to an age-related reduction in glomerular filtration rate.

Altered water excretion in healthy elderly men

http://www.clinsci.org/content/ppclinsci/64/2/61P.3.full.pdf

M. J. Crowe

Papers

Reduced Thirst after Water Deprivation in Healthy Elderly Men

Altered water excretion in healthy elderly men

Reduced Thirst in the Elderly after 24-Hour Water Deprivation

Thirst in the elderly.