Principles of drug therapy in the elderly

Definition of the problem. Drug therapy in old age is the art of matching a drug to a body whose handling of and response to drugs has changed, in a patient who usually has several diseases and takes several drugs at once.

Scale of the problem. Older people are the largest consumers of drugs. Adverse drug reactions (ADRs) account for a large share of emergency hospital admissions in this age group and are largely preventable (Pathy, Ch. 10).

Frail elders are excluded from trials. Frail older people are rarely included in large drug trials, so results from younger patients are often wrongly extrapolated to them (Pathy, Ch. 11).

The therapeutic window narrows with age. The gap between a therapeutic dose and a toxic dose becomes smaller, so the more aggressive the treatment, the greater the chance of harm (Essentials, Fig. 5-2).

Non-pharmacological factors matter more than pharmacology. Most of the steps that make drug therapy safe — correct diagnosis, correct choice, correct taking of the drug — come before pharmacokinetics ever apply (Essentials, Fig. 14-1).

Absorption — least affected. Splanchnic blood flow, absorptive surface and motility fall and gastric pH rises, but no clinically important change in absorption occurs unless there is gut disease (e.g. diabetic gastroparesis).

Distribution — protein binding. Serum albumin falls in illness and malnutrition (a negative acute-phase reactant); highly protein-bound drugs therefore have a higher free (active) fraction. Reported "therapeutic ranges" were defined in younger subjects and may mislead.

Distribution — volume of distribution (Vd). ↓ Total body water and lean mass → ↓ Vd for water-soluble drugs → higher plasma levels, toxicity with early doses: digoxin, aminoglycosides, atenolol, sotalol, theophylline, hydrochlorothiazide, lithium, alcohol. ↑ Total body fat → ↑ Vd for fat-soluble drugs → prolonged half-life, toxicity after steady state: amiodarone, diazepam, desipramine, haloperidol.

Metabolism. Liver blood flow, enzyme activity and enzyme inducibility all fall. Phase I reactions (oxidation, reduction, hydrolysis) decline — more so in men; Phase II (conjugation, acetylation, glucuronidation) is relatively preserved. First-pass metabolism is reduced. Normal liver function tests do not mean normal drug metabolism.

Excretion — the most predictable change. Renal blood flow, GFR and tubular secretion all decline. Renally cleared drugs accumulate, with longer half-lives and higher steady-state levels.

Serum creatinine is misleading. Muscle mass falls with age, so creatinine production falls; a "normal" creatinine may hide substantially reduced renal function. Estimate clearance (Cockcroft–Gault / eGFR), but remember there is wide interindividual variation — average declines must not be applied blindly to an individual.

Sensitivity may rise or fall. Receptor number and affinity, second-messenger function and nuclear responses all alter. Older patients are more sensitive to benzodiazepines, opioids, anticholinergics and other psychotropics, but less sensitive to beta-adrenergic agonists and antagonists.

Reduced homeostatic reserve. Blunted baroreflex, thermoregulation and thirst mean drugs more readily cause postural hypotension, falls, hypothermia and dehydration.

Make the diagnosis first. Symptoms are under-reported, vague, multiple and often atypical; treating a symptom with a drug instead of evaluating it is the commonest route into polypharmacy.

"Start low and go slow" — but do not under-treat. Begin with the lowest effective dose of the most cost-effective agent and titrate slowly; still increase to the maximum appropriate dose if the response requires it.

One drug at a time; simplify. Use as few drugs as possible, prefer once-daily dosing, keep all drugs on the same schedule and tie doses to a daily routine.

Treat every new symptom as a possible ADR. Never treat a symptom with a new drug before considering stopping the offending one — this avoids the prescribing cascade.

Consider drug–disease as well as drug–drug interactions (Essentials, Table 14-4): diuretics → incontinence and dehydration; beta-blockers → masked hypoglycaemia, bronchospasm; anticholinergics → retention, glaucoma, constipation; NSAIDs → heart failure; antipsychotics → worsening parkinsonism.

Support adherence actively. Barriers include poor vision and hearing, low literacy, memory impairment, transport, cost, and child-proof containers. Use pill boxes and drug calendars, involve family and pharmacists, and reconcile medicines at every hospital discharge.

Review, record and prune. Keep an updated medication record reviewed at each visit; ask patients to bring all bottles ("brown-bag" review); each time a drug is added, ask whether one can be stopped. Never be the first to use a new drug in an older person, and never the last to abandon an old unsafe one.