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Pharmacokinetics in the older patient

The medicines management of an older person is complicated by factors such as multiple diseases, complex medication regimes and the aging process. Safely administering medication to the older person is a significant and critical challenge when ensuring patient care.1

In general drug absorption, distribution in the body, activity, metabolism and excretion can all change as a result of ageing. The older person is more likely to experience side effects as well as experiencing difficulty in swallowing their medication.1

A common response to an issue swallowing medication is to crush tablets or open capsules.2 Any change, like crushing tablets, can alter its absorption characteristics. This may result in changes in the drug pharmacokinetics and bioavailability resulting in underdosing or adverse effects.3

Elderly patient with tablets in hand Nurse with Elderly Patient

Drug absorption

Tablets or capsules are designed to allow the release of a drug over a time period into the blood. If the stomach is full or empty, this may affect the speed at which absorption occurs and the amount of drug which is absorbed.1

Numerous gastrointestinal changes occur as part of the ageing process however, this doesn’t appear to have a significant impact on drug absorption. The effect of polypharmacy should be considered and monitored in older patients, it’s important to recognise the impact that co-prescribed drugs may have on drug absorption.4

Drug distribution

Once a drug is absorbed it’s 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 solubility in fatty tissues.1

Drug distribution is affected by the changes in body composition associated with age due to an increase in body fat percentage and decrease in lean muscle mass. There is also a decrease in total body water. As drug distribution is largely dependent on body composition, there may be a requirement to reduce the dosage or dosing interval.4

Drug metabolism

Drug metabolism is the process by which the body chemically breaks down or changes a drug allowing for the eventual elimination from the body. Most metabolism takes place in the liver, although it can occur in other areas of the body such as the intestines. Drugs which are metabolised quickly have a short duration of action and need to be administered more frequently, whereas those which are metabolised more slowly will need administration less often. In general, as drugs are metabolised their therapeutic effect diminishes.1

Liver metabolism

Several age-related changes are known to influence liver function. These include:

  • Reduction in total liver size
  • Reduction in liver blood flow (up to 58% 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.1

Liver enzymes - inducers and inhibitors

Certain drugs cause induction of liver enzymes resulting in faster metabolism of some other drugs whilst drugs called enzyme inhibitors reduce the action of the liver enzymes resulting in slower metabolism of other drugs. This effect is of importance when one of these enzyme affecting drugs is started, stopped or the dose changed, and is especially important in older patients who may be on several medications at any one time.1

Elderly couple Elderly Male Patient Taking Pills With Water

Drug elimination

Once drugs have had their desired effect, they need to be eliminated by the body. Excretion predominantly occurs via renal elimination in the kidneys.1

Renal Excretion

The total size of the kidneys decreases with age, as does the number of functioning nephrons. There is also decreased renal blood flow with increasing age.1 Aging is also accompanied by a reduction in both glomerular function and tubular function. It has been suggested that by the age of 90, there may be a 30-40% reduction in renal function. Renal function may also be affected by the presence of a coexisting disease, which are common in the elderly. Decreased renal function, results in a reduction in drug clearance, older patients may therefore require lower or less frequent doses.4

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View References

1. Medicines Management and Older People- a guide for healthcare professionals. Edited by R Greenwall. August 2016. | 2. Strachan, I & Greener, M. (2005) Medication-related swallowing difficulties may be more common than we realise. Pharmacy in Practice. Volume 15; issue 9; p411–414. | 3. Royal Pharmaceutical Society. Pharmaceutical Issues when Crushing, Opening or Splitting Oral Dosage Forms. June 2011. Available at: https://www.rpharms.com/Portals/0/RPS%20document%20library/Open%20access/Support/toolkit/pharmaceuticalissuesdosageforms-%282%29.pdf (accessed 16th April 2020) | 4. Hughes. S,J. Prescribing for the elderly patient: why do we need to exercise caution? BRJ Clin Pharmacol 1998; 46: 531-533.

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