17th May 2025

Prescribing in Old Age

Physiological changes in the elderly

With increasing age, many physiological changes may alter pharmacokinetics. These include:

• Increased gastric motility
• Reduced intestinal blood flow
• Lower body weight and lean body mass
• Higher proportion of body fat
• Lower hepatic and renal blood flow (and thus glomerular filtration rate)
• Change in immune response

All these factors alter pharmacokinetics:

• Absorption of most drugs remains the same except for reduction in iron, calcium and thiamine absorption
• Lower concentration of fat-soluble drugs
• Higher concentration of water-soluble drugs
• Lower rate of drug metabolism and hepatic clearance
• Less efficient renal drug excretion

Pharmacodynamic changes that also occur simultaneously are as follows:

• Central nervous system becomes more sensitive to sedative medications
• Less effective homeostatic mechanisms and less able to compensate for side effects (especially postural hypotension)
• Reduced clotting factor synthesis
• Increased risk of adverse and allergic reactions

Together with the fact that polypharmacy is more prevalent in the elderly, up to 97% in hospitalised patients, they are also more likely to experience side effects secondary to drug interactions.

Table 1. Common fat-soluble and water-soluble drugs

Delirium

Delirium is an acute global disorder of the central nervous system function characterised by altered cognition, awareness, and attention.

As elderly patients’ central nervous system become more sensitive to neurochemical imbalances, all sedative medications can easily cause decompensation and delirium:

• Opioids
• Benzodiazepines
• Z-drugs for insomnia
• First generation antihistamines
• Antidepressants
• Antipsychotics
• Anticholinergics
• Antiemetics
• General anaesthesia

Steroids are well known to cause confusion and cognitive impairment, and in severe cases, hallucinations and delusions.

Medications that cause arrhythmias also have the potential to cause delirium. For instance, beta blockers and Digoxin cause bradycardia and may disrupt blood flow to the brain.

Anticholinergic burden

Anticholinergic medications are associated with many side effects to which the elderly are more susceptible:

• Cognitive impairment
• Confusion
• Drowsiness
• Ataxia
• Headache
• Hallucination
• Blurred vision (due to dry eyes)
• Dry mouth
• Nausea and vomiting
• Tachycardia and palpitations
• Urinary retention
• Constipation
• Reduced sweating

Anticholinergics not only can precipitate acute conditions such as acute closed angle glaucoma, but they are also associated with higher chance of hospital admission, longer length of stay and greater incidence of falls. Therefore, they should be avoided in elderly patients if possible.

Anticholinergic burden (ACB) is the cumulative measure of anticholinergic effect on an individual taking one or more drugs with anticholinergic activity. The ACB score for each patient can be calculated by adding up the score of each medication they are taking. A higher score represents a higher likelihood of adverse effects. Each 1-point increase in ACB total score is suggested to result in decline of MMSE score of 0.33 points and around 80% increase in mortality risk over 2 years.

Table 2. ACB score for different drugs

Levodopa is often combined with a peripheral blocker of dopamine metabolism for managing Parkinson’s disease, such as dopa decarboxylase inhibitor (e.g., Carbidopa, Benserazine), monoamine oxidase B (MAO-B; e.g., Selegiline, Rasagiline), and catechol‑O‑methyl transferase (COMT) inhibitor (e.g., Tolcapone, Entacapone). Topical dopamine agonist in the form of a patch, usually containing Rotigotine, can be given to patients who cannot comply with oral medications. First generation antipsychotics should be avoided in Parkinson’s patients as they can exacerbate extrapyramidal symptoms (EPS). Management of drug-induced EPS is Procyclidine.

In patients with dementia, antimuscarinics can more easily cause decompensation of cerebral function and delirium. When prescribing and reviewing an elderly patient’s drug chart, we should be aware of the high ACB medications and try to switch them to drugs with lower ACB scores.

Medicine reconciliation

Polypharmacy is the concurrent use of 4 or more regular medications in an individual. It can be appropriate in many instances in patients with complex comorbidities, but clinicians must be able to recognise inappropriate polypharmacy that is much more common in older people.

Problems & consequences of inappropriate polypharmacy include:

• Adverse drug interactions
• Pill burden
  • Poor compliance
  • Confusion as to what, when and how to take drugs
  • Sense of lack of control over own healthcare
• Increased hospital admission and healthcare cost

Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START) are evidence-based guidelines used in the United Kingdom aimed to prevent inappropriate prescribing and omission of essential medicines (seeTable 3). Utilising STOPP/START criteria has reduced the number of adverse drug events and medical costs, whilst improving activities of daily living.

Table 3. Summary of STOPP guidance

As a general principle, any duplication of drug class should be reviewed and preferably removed to reduce side effects and polypharmacy. Avoid concurrent use of several sedative medications due to increased risk of overdose and respiratory depression.

Despite general clinical consensus regarding stopping anticoagulants in recurrent falls, there has not been any evidence supporting this. Starting or stopping anticoagulants for specific indications (e.g., atrial fibrillation) should be based on a balance of risks between risk of thrombotic event and bleeding risks. Scoring systems should be utilised to make an informed decision (i.e. CHA2DS2-VASc score for risk of cerebrovascular event in atrial fibrillation, ORBIT and HASBLED for risk of bleeding).

Table 4. Summary of START guidance

Warfarin is an important medication to take note of when starting or stopping medications as many drugs can affect its anticoagulant effect, mainly by potentiating or inhibiting the cytochrome P450 system responsible for metabolising warfarin. When starting any drugs that can alter warfarin metabolism (Table 5), monitor international normalised ratio (INR) closely and modify warfarin dose if necessary. Several antibiotic classes and antiepileptic drugs (AED) are the most common causes. Patients will also need to be reminded that some food items should be avoided to maintain a stable Warfarin level. Patients with liver disease are likely to have impaired Warfarin metabolism, thus a lower dose may be required to achieve target INR.

Table 5. Drugs that alter warfarin anticoagulant effect

Below is a simple guide as to how to reconcile and review medications for elderly patients:

• Remove medications that are not indicated by their current conditions
• Limit the range of drug class to reduce possible drug-drug interactions
• Start with lower dosage within the effective range, and titrate according to symptoms slowly if necessary
• Simplify regimen and keep the number of doses per day to a minimum
• Review regularly, especially at each admission and change in condition