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There has been a great increased in the understanding of physiological changes of ageing. Ageing decreases in physiological fitness and reduce the ability to respond to the external environment. This can result in fail to maintain homeostasis under conditions of physiological stress. Ageing can cause loss of function units; these units play a major role in performing physiological activities characteristics of the organs. Ageing individuals are very fragile because of the sarcopenia syndrome as well as neuroendrocrine and immune dysfunctions. They are also prone to disease and multimorbitlity. The physiological changes within ageing can affect pharmacokinetics of drugs and the dosage of drugs used in elderly patients. There are also important age-related physiological changes and age- related changes in pharmacokinetics to be discussed. Effects of ageing on pharmacokinetics of digoxin will be discussed. Dosage of digoxin should be monitored in elderly.
Ageing changes the structure of the cardiac tissues and chambers; it reduces the elasticity and compliance of the aorta and great arteries. An increase in vascular intimal thickness can lead to early stages of atherosclerosis. Aging increases in vascular stiffness which elastin to fragmentation which can result in a higher systolic artieral pressure. An increased in the thickness of the left ventricular wall can decrease number of myocytes and increase left ventricular myocyte size and changed growth factor regulation. This can result in slowed early diastolic cardiac filling and increased cardiac filling pressure. An increased in the left atrial size will increase the left atrial pressure and volume which can result in the lone atrial fibrillation. Ageing also changes some functions of the cardiovascular system; decreased cardiovascular reserve and changes in the regulation of vascular tone. Decreased cardiovascular reserve would result in lowering threshold for and increased servity of heart failure. And changes in the regulation of vascular tone would results in vascular stiffening and hypertension.
Ageing changes the renal system and it can affect the pharmacokinetics of some drugs. These changes are renal blood flow, glomerular filtration rate, tubular function and creatine clearance. The renal blood flow decreases from 1200mL/minute at 30 ââ‚¬" 40 year old to 600mL/minute at age 80. This is because the intra-renal vascular changes, consisting of hyalinization of the vascular turft leading it to reduced the renal blood flow in the afferent arterioles in the cortex. The most important functional defect was the declined glomerular filtration rate, creatinine is also declined because of aged related loss of muscle mass.
These have important pharmacokinetic implications. They include the following changes.
(i) A decrease in total body water, causing a decrease in the central compartment (V1). This will result in higher peak drug concentrations following boluses or rapid infusions. Lean body mass is a better predictor than total body weight for determining initial dosages for both hydrophilic and lipophilic drugs. (ii) A decrease in lean body mass causes a decrease in the rapid equilibrating compartment (V2). (iii) An increase in body fat causes an increase in the slow equilibrating compartment (V3), leading to increased total volume of distribution and alterations in the duration of drug effect. 
Central nervous system
These occur at different rates and magnitudes, resulting in a heterogeneous change, but globally between the ages of 20 and 80 years there is approximately a 30% decrease in cerebral blood flow, a 36% decrease in cerebral oxygen consumption, and a 30% decrease in cortical neuronal density
The physiological changes of ageing on drug absorption effects the GI motility, increases in gastric pH, reduced gastric acid secretion and gastric emptying and absorptive capacity of the small intestines. This may cause a reduction in the rate of absorption in some drugs. Drugs such as digoxin have a slower rate of absorption in the elderly group as indicated by an increased time to the plasma concentration.
However, the extent of
digoxin absorption was similar in the 2 groups and
it is reasonable to conclude that age does not impair
drug absorption to a clinically relevant degree. In
some patients, intestinal microflora may metabolise
digoxin causing reduced drug bioavailability
and these patients may require higher than usual
dosages to achieve steady-state plasma drug concentrations.
Patients with malabsorption syndromes
or GI reconstruction may require higher
dosages of digoxin but this is not specific to older
Though liver function tests are unchanged with age, there is some overall decline in metabolic capacity.
Decreased liver mass and hepatic blood flow
Highly variable, no good estimation algorithm
Minimal clinical manifestations
Age-related decreased renal blood flow and GFR is well-established.
Decreased lean body mass leads to decreased creatinine production
EFFECTS OF DIGOXIN
can cause anorexia, confusion even at therapeutic drug levels
Renal excretion can change over time as age-related renal function declines.
0.125mg/day most often adequate