The pharmacokinetics and pharmacodynamics of most drugs are altered to an important extent in older people. These changes in drug handling and action must be taken into account if treatment is to be effective and adverse effects minimised. Older people often have a number of concurrent illnesses and may require treatment with several drugs. This leads to a greater chance of problems arising because of drug interactions and a higher rate of drug-induced problems in general.1 It is reasonable to assume that all drugs are more likely to cause adverse effects in older patients than in younger patients (Box 6.1).
As we age, control over reflex actions such as blood pressure and temperature regulation is reduced. Receptors may become more sensitive. This results in an increased incidence and severity of adverse effects. For example, drugs that decrease gut motility are more likely to cause constipation (e.g. anticholinergics and opioids) and drugs that affect blood pressure are more likely to cause falls (e.g. tricyclic antidepressants [TCAs] and diuretics). Older people demonstrate an exaggerated response to central nervous system (CNS)-active drugs such as benzodiazepines and opioids. This is partly because of an age-related decline in CNS function and partly due to increased pharmacodynamic sensitivity to these drugs (due to increased blood-brain barrier permeability).2, 3 Therapeutic response to medication can also be delayed; for example, older adults may take longer to respond to antidepressants than younger adults.4
Older people may be more prone to developing serious adverse effects such as agranulocytosis5 and neutropenia6 with clozapine, stroke with antipsychotic drugs7 and bleeding with selective serotonin reuptake inhibitors (SSRIs).8
Gut motility decreases with age, as does secretion of gastric acid. This leads to drugs being absorbed more slowly, resulting in a slower onset of action. In general, the same amount of drug is absorbed as in a younger adult, but the rate of absorption is slower.
Older adults have more body fat, less body water and less albumin than younger adults. This leads to an increased volume of distribution and a longer duration of action for some fat-soluble drugs (e.g. diazepam), higher concentrations of some drugs at the site of action (e.g. digoxin) and a reduction in the amount of drug bound to albumin (increased amounts of active ‘free drug'; e.g. warfarin, phenytoin).
The majority of drugs are hepatically metabolised. Liver size is reduced in the elderly, but in the absence of hepatic disease or significantly reduced hepatic blood flow, there is no significant reduction in metabolic capacity. The magnitude of pharmacokinetic interactions is unlikely to be altered but the pharmacodynamic consequences of these interactions may be amplified.
Renal function declines with age: 35% of function is lost by the age of 65 years and 50% by the age of 80.
More function is lost if there are concurrent medical problems such as heart disease, diabetes or hypertension. Measurement of serum creatinine or urea can be misleading in the elderly because muscle mass is reduced, so less creatinine is produced. It is particularly important that estimated glomerular filtration rate (eGFR)11 is used as a measure of renal function in this age group. It is best to assume that all elderly patients have at most two-thirds of normal renal function.
Most drugs are eventually (after metabolism) excreted by the kidney. A few do not undergo biotransformation first. Lithium and sulpiride are important examples. Drugs primarily excreted via the kidney will accumulate in the elderly, leading to toxicity and adverse effects. Dosage reduction is likely to be required (see Chapter 8).
Some drugs have a narrow therapeutic index (a small increase in dose can cause toxicity and a small reduction in dose can cause a loss of therapeutic action). The most commonly prescribed ones are digoxin, warfarin, theophylline, phenytoin and lithium. Changes in the way these drugs are handled in older people and the greater chance of interaction with other drugs mean that toxicity and therapeutic failure are more likely. These drugs can be used safely but extra care must be taken and blood concentrations should be measured where possible.
Some drugs inhibit or induce hepatic metabolising enzymes. Important examples include some SSRIs, erythromycin and carbamazepine. This may lead to the metabolism of another drug being altered. Many drug interactions occur through this mechanism. Details of individual interactions and their consequences can be found in the British National Formulary (BNF) online for individual drugs.12 Most can be predicted by a sound knowledge of pharmacology.
Adherence to the following principles will reduce drug-related morbidity and mortality:
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Sometimes patients refuse treatment with medicines, even when such treatment is thought to be in their best interests. In the UK, where the patient has a mental illness or has capacity, the Mental Health Act should be used, but if the patient lacks capacity this option may not be desirable. Medicines should never be administered covertly to older patients with dementia without a full discussion with the multidisciplinary team (MDT) and the patient's relatives. The outcome of this discussion should be clearly documented in the patient's clinical notes. Medicines should be administered covertly only if the clear and express purpose is to reduce suffering for the patient. (For further information, see ‘Covert administration of medicines within food and drink' later in this chapter.)
For advice on dosing of psychotropics in older people, see ‘A guide to medication doses of commonly used psychotropics in older adults' later in this chapter.