Older people are more likely to be on multiple medicines. People over 60 make up 20% of the population but receive 52% all prescriptions., and in the over 75 age group 36% are taking four or more medicines (termed polypharmacy) (Dept of Health, 2001). This high prevalence of medication use, together with co morbidity and changes in pharmacokinetics and pharmacodynamics increases the risk of encountering adverse drug reactions and drug interactions when you prescribe for this patient group.

What pharmacokinetic changes take place in the older person?

Pharmacokinetics (see basic pharmacology section) describes how the body handles medicines, and consists of four stages: absorption, distribution, metabolism and excretion. Important age related changes occur principally with distribution, excretion and metabolism (Mangoni and Jackson, 2003).

Digoxin prescribing

Look up digoxin in the BNF – what advice is given under cautions for dosing in older people? Discuss with a colleague what this advice might mean in clinical practice

Distribution

With increasing age the proportion of body fat increases and the proportion of body water decreases. For water soluble drugs the smaller proportion of body water means that the same dose results in higher serum levels in older people, examples of this include digoxin and gentamicin. As you will have seen in the BNF from the activity above, the loading dose of digoxin should be reduced in older people. For fat soluble drugs distributing into the larger proportion of body fat, the main result is a prolonged half-life i.e. it takes longer to clear a dose from the body, with an increased risk of accumulation if doses are not adjusted. An example of this is nitrazepam. This is a long acting benzodiazepine, and the half-life increases from approximately 30 to 40 hours in the older person, making it an inappropriate choice for night sedation, as significant drug levels are still likely to be present the following morning which may increase the risk of falls and confusion.

Excretion

The principle organ responsible for excretion of medicines in the body is the kidney. With increasing age, renal function declines at a mean of about 1% a year, but with large variability between patients (Lindeman 1992). Co-morbidity such as heart failure and diabetes can also worsen renal function, making it important that you check renal function in older people and adjust doses accordingly. See the section on renal impairment later in this chapter for how to do this in practice.

Metabolism

Although there is an age related decline in hepatic blood and liver volume, the large reserve of the liver means that you are unlikely to need to adjust doses of medicines metabolised in the liver in unless there is evidence of liver disease. This is dealt with later in this chapter.

What pharmacodynamic changes take place in the older person?

Pharmacodynamics describes what the medicine does to the patient (see Basic Pharmacology section). In general older people have increased sensitivity to medicines, even allowing for the changes in serum levels that may occur as a result of pharmacokinetic changes. Most commonly this is due to a decline in homeostatic reserve. Some common examples are given below.

Postural hypotension

The normal homeostatic response to maintain blood pressure on standing is tachycardia and vasoconstriction, both of which may be impaired in older people. Medicines that inhibit this response are more likely to produce postural hypotension which may increase the risk of falls. Examples include beta blockers (inhibition of tachycardic response) and medicines with vasodilatory side effects (e.g. calcium channel blockers, nitrates, alpha blockers). Medicines that are central nervous system (CNS) depressants (e.g. opiates, benzodiazepines) may also decrease sympathetic outflow and increase postural hypotension. Falls in the older person are a major cause of morbidity and mortality, and national guidance recommends that you should review medicines that may have contributed to falls as part of a wider multifactorial assessment in those who fall (NICE, 2004).

Postural sway

Postural stability is impaired in older people, and medicines that increase postural sway such as benzodiazepines and opiates may contribute to an increased risk of falling.

Cognitive function

Medicines that act on the CNS way worsen cognitive function, particularly where there is pre-existing cognitive impairment. Examples include antidepressants, antipsychotics, benzodiazepines, and opiates. Cholinergic transmission is considered to play an important role in cognitive function, with the result that medicines with anticholinergic side effects (e.g. oxybutynin, hyoscine, and amitriptyline) may lead to confusion in older people. When older people present with acute confusion or delirium you should always review their medicines for potential causative agents.

Visceral muscle function

Constipation is more common in older people, and drug therapy is often one of the contributing factors. Anticholinergics, opiates, tricyclic antidepressants may worsen constipation and you should review these if possible before further medicines are added to treat the constipation. Urinary retention may be a problem in older males with benign prostatic hypertrophy, and medicines with anticholinergic side effects may contribute to this as they reduce smooth muscle contraction in the bladder. Conversely, bladder instability with symptoms of urge incontinence is more common in older people, and use of diuretics may worsen this problem. When you prescribe loop diuretics (e.g. furosemide) you should instruct your patient to take doses no later than 2pm, otherwise diuresis is likely to continue after bedtime

Renal function

As discussed above renal function declines with age. As well as the effect this has on the excretion of medicines, declining renal function will also mean there is less homeostatic reserve. You should monitor renal function closely if you need to prescribe medicines that may further reduce renal function, particularly when used in combination with each other. Examples include diuretics, ACE inhibitors, NSAIDS and gentamicin.

What other high risk medicines are there in older people?

From the examples described above, you can see that the two most important classes of medicines that require you to be cautious when prescribing in the older person are medicines that act on the central nervous system, and medicines acting on the cardiovascular system. There are some other classes of medicines that also require careful use in older people

Warfarin Prescribing

Look for a warfarin prescription chart or guidelines in your hospital. What is the suggested regime for loading in older people? If you were considering starting warfarin for an older person what patient factors might influence whether you think this medicine would be safe to use in your patient?

Warfarin

Older people are more sensitive to warfarin and require lower doses. Most warfarin loading guidelines suggest a lower loading dose of 5mg rather than 10mg in younger adults. Safe use of warfarin requires regular blood tests for INR and subsequent dose adjustment. If patients have cognitive impairment, you should consider whether there is sufficient support in place from carers to allow this process to take place safely.

Non-steroidal anti-inflammatory drugs

Gastrointestinal bleeding is the most important adverse effect of NSAIDS, and older people are more at risk of this adverse effect. Compared to the people aged 25 to 49 years, people aged 60-69 had 2.4 times the risk of a serious gastrointestinal complication, while those aged 70-80 were found to have 4.5 times the risk (Herandez-Diaz and Rodriquez, 2000). Current guidance suggests that you should always prescribe a gastro-protective agent with a NSAID, normally a proton pump inhibitor (e.g. lansoprazole or omeprazole. NSAIDS also reduce renal function and may worsen cardiac failure.

Hypoglycaemic medicines

In older people with diabetes, hypoglycaemia can lead to significant morbidity and even mortality. Long acting sulphonylureas such as glibenclamide are more likely to cause hypoglycaemia and should be avoided, shorter acting agents such as gliclazide are preferred.

Other risk factors for medicine related problems in older people

Aside from use of high risk medicines, other factors have been identified as important factors associated with medicines related problems in older people (DoH, 2001)

Other risk factors

What other factors can you think of that might be likely to lead to medicine related problems in older people? Discuss your responses with a colleague to see if you have come up with similar ideas