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Key advisor: Professor John Campbell,
Dunedin School of Medicine (Geriatric Medicine), University of Otago
Expert Reviewer: Associate Professor Ngaire Kerse,
Deparment of General Practice and Primary Healthcare (Gerontology), University of Auckland

Prescribing decisions for elderly people are difficult because:

  • Physiological changes in elderly people often result in different and more severe drug related problems
  • High rates of co-morbidity and polypharmacy increase the risk of interactions with other drugs and other illnesses

The results of drug trials are often difficult to apply to elderly people

Physiological changes in elderly people result in different and more severe drug related problems

Age related changes in pharmacokinetics and pharmacodynamics result in altered responses to many medications. These changes include decreased glomerular filtration rate, renal tubular filtration, gastric acid secretion, gastrointestinal motility, gastrointestinal surface area for absorption, splanchnic perfusion and hepatic size and perfusion.

Drug absorption, first-pass metabolism, protein binding, distribution and elimination are all affected. Overall this results in decreased clearance and greater exposure to the drug. Due to these physiological changes, certain drugs are associated with an increased risk of adverse drug reactions (Table 1).

Table 1: Drugs commonly associated with adverse reactions in elderly people.
Drug or drug class Comments
All drugs Start low, go slow. Many drugs, e.g. oxybutynin, antipsychotics, TCAs and antihypertensives need much lower doses in elderly people.
Benzodiazepines Those with a long half-life, such as diazepam and nitrazepam cause excessive and prolonged sedation. Temazepam is a better choice if necessary but all are best avoided.
Dextropropoxyphene Can cause confusion and excessive sedation in elderly people. Avoid
use.
Digoxin Use low doses initially. Extra vigilance required for those who need to be
on higher doses.
Indomethacin This NSAID has a high incidence of CNS effects and gastrotoxicity.
Nefopam (Acupan) CNS effects and marked anticholinergic actions. Avoid use.
NSAIDs Use lowest effective dose for the shortest necessary duration. Avoid long-term use of full dose, longer half-life drugs such as naproxen and piroxicam.
Tricyclic antidepressants (TCAs) Nortriptyline is the recommended first choice TCA in elderly people.
Doxepin and amitriptyline are very sedating and have strong anticholinergic actions. They are not recommended as a first choice for depression in elderly people.

Reduced renal clearance in elderly people reduces excretion of many drugs, increasing the risk of adverse effects. Acute illness, especially dehydration, may cause further reductions in renal clearance, with the potential to move some drugs (e.g. digoxin) from the therapeutic to the toxic range without alteration in dose.

Elderly people have reduced ability to maintain homeostasis, often resulting in postural hypotension and impairment of thermoregulation, cognitive function and visceral muscle function. This means that increased symptoms may occur because of the body's inability to compensate for small perturbations in function from drug effects.

Altered molecular and cellular responses to drugs occur in elderly people. For example there are decreased density and/or affinity of receptors in specific receptor sites and target organs. Therefore, increasing the dose of a drug may have little effect on the target response but substantially increase adverse effects.

High rates of co-morbidity and polypharmacy increase the risk of interactions with other drugs and other illnesses

Increasing co-morbidity results in polypharmacy and increases the risk of:

  • Drug-illness interactions
  • Polypharmacy and drug interactions

Drug-illness interactions are common in elderly people

The increased frequency in elderly people of co-existing illnesses, places them at particular risk of drug-illness interactions. For example, many elderly people have both heart failure and arthritis. NSAIDs used for pain relief can adversely affect the heart failure, particularly if there is a degree of impaired renal function.

Polypharmacy increases the risk of drug interactions

The majority of elderly people take multiple medications. Latest data from the Pharmaceutical Data Warehouse (NZHIS) indicates that most people over 70 who have been dispensed any medication, are on at least four medications (Figure 1).

Figure 1: Number of unique dispensed medications in patients aged 70 or over in a six month period.
(Notes: Study period was March to August 2007, study group included people over 70 who were dispensed one or more medication in the time period)

A steady increase in the likelihood of adverse reaction has been reported in a population of patients discharged from a hospital; from 10% of people taking two drugs to 100% of those taking twelve medications experiencing an adverse drug reaction. High prescribing rates were associated with more severe illness.1

The results of drug trials are often difficult to apply to elderly people

As the absolute risk of many adverse outcomes increases with age, the number needed to treat (NNT) for interventions for these conditions might be expected to fall. The absolute risk of a cardiovascular event is high for elderly people, and there is evidence that anti-hypertensive treatment is beneficial. For example, the Hypertension in the Very Elderly Trial (HYVET) which commenced in 2001, was halted early due to detection of a significant reduction in strokes and cardiovascular mortality in the patients receiving treatment.

While the HYVET study is highly relevant to the elderly population, there is a lack of relevant evidence in other areas. Guidelines for clinical practice are largely based upon clinical trials which are problem focused, utilise single disease models, and exclude elderly people.2 When elderly people are enrolled in a trial, they are usually a highly selected group, as people with co-morbidities and polypharmacy are excluded.3 This means the results of drug trials are often difficult to apply to the elderly people seen in primary care.

References

  1. Williamson J, Chopin J. Adverse reactions to prescribed drugs in the elderly: A multicentre investigation. Age Ageing 1980; 9(2):73-80.
  2. Bugeja G, Kumar A, Banerjee AK. Exclusion of elderly people from clinical research: a descriptive study of published reports. BMJ 1997; 315(7115):1059.
  3. Bene J, Liston R. The special problems of conducting clinical trials in elderly patients. Rev Clin Gerontol 1997; 7(1): 1-3.