In general drug absorption, distribution in the body, activity, metabolism and excretion can all change as a result of ageing. In addition it is common for multiple medical conditions to be present in older patients which can lead to a greater potential for medication problems due to polypharmacy.
Any change that may affect the rate of absorption, metabolism or excretion of a drug may also effect whether that drug reaches toxic levels or drops to sub-therapeutic levels.
Tablets or capsules are designed to allow the full release of the drug over a specific time schedule. If the stomach is full or empty, this may affect the speed at which absorption occurs. Drug absorption is theoretically reduced in the older patient due to loss of mucosal intestinal surface, decrease in gastrointestinal blood flow and reduced gastric acidity.
Once a drug is absorbed it is carried around the body in the blood stream. Distribution is the term used to describe the movement of the drug into body tissues. The extent and pattern of distribution will be dependent mainly on the plasma and tissue protein binding characteristics of the drug and its lipid solubility (solubility in fatty tissues). Drug distribution is affected by the changes in body composition associated with age.
Altered plasma protein concentrations and individual body composition, in particular body fat and intracellular fluid content, can significantly influence drug distribution in the older patient. The decreased muscle and tissue mass that accompanies ageing will also influence the distribution of certain drugs, as will the reduced blood flow to tissues and organs. Active uptake into tissues may also be influenced by ageing. There is also evidence that the blood-brain barrier is less intact in older patients thus allowing certain drugs to distribute into the brain in increased concentration.
The two main routes by which drugs are eliminated from the body are:
- Metabolism by liver enzymes
- Excretion by the kidneys
Several age related changes are known to influence liver function. These include:
- Reduction in total liver size
- Reduction in liver blood flow (40-50% reduction between 25 and 65 years of age)
The reduction in total liver size would be expected to result in a decrease in the levels of drug metabolising enzymes. A further decrease in efficiency would be expected to result from the reduction in liver blood flow as this would result in a decrease of exposure of the drug to metabolising enzymes.
Liver enzymes - inducers and inhibitors
Certain drugs cause induction of liver enzymes resulting in faster metabolism of some other drugs whilst other drugs called enzyme inhibitors reduce the action of the liver enzymes resulting in slow metabolism of other drugs. This effect is of particular importance when one of these enzyme affecting drugs is started, stopped or the dose changed, and is especially important in older patients who many be on several medications at any one time.
The kidneys remove substances from the blood and eliminate them in the urine. The total size of the kidneys decrease with age, as does the number of functioning nephrons. There is also decreased renal blood flow with increasing age. This will result in a progressive decrease in renal function as demonstrated by measures of the glomerular filtration rate (GFR). By the age of 70, both renal blood flow and the GFR will have decreased on average by about 35% from the age of 20.
In older people, renal clearance is frequently aggravated by the effects of enlarged prostate or chronic urinary tract infection. Acute illness may lead to rapid reduction in renal clearance, especially if accompanied by dehydration. Hence a patient stabilised on a drug with a narrow therapeutic index (the difference between effective and toxic dose being small) may rapidly develop adverse effects in the event of an acute illness.
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