7.

Drug therapy in the elderly

The proportion of elderly people in the population is increasing steadily in economically developed
countries. The elderly are subject to a variety of complaints, many of which are chronic and
incapacitating, and so they receive a great deal of drug treatment.

Adverse drug reactions and drug interactions become more common with increasing age.

The importance of considering drug therapy in the elderly is because :

 In most develop countries, the elderly constitute about 12 % of the popn but they consume 25-
30% oh health service expenditure
 Adverse drug reactions are 2 – 3 times more common in the elderly than in young and middle-
aged adults
 The error rate in taking drugs is about 60% in pts over 60 years of age and the rate of error
increases if more than 3 drugs are prescribed
 Drug elimination becomes less efficient with increasing age, leading to drug accumulation during
chronic dosing
 Homeostatic mechanisms become less effective with advancing age, so individuals are less able
to compensate for adverse effects, such as unsteadiness or postural hypotension
 The central nervous system becomes more sensitive to the actions of sedative drugs
 Increasing age produces changes in the immune response that can cause an increased liability to
allergic reactions

There are several factors in the elderly which signal potential trouble, and the more of these factors
which are common to an elderly pt, the more likely it is that one will encounter difficulty with drug
therapy. The important factors are frailty, the degree of illness, inability to look after themselves, poor
appetite and nutrition, poor fluid intake, immobility, multiple illnesses, confusion & forgetfulness, and
lack of supervision. Some of these factors lead to problems with compliance, the use of wrong dosages
and wrong drugs (e.g from hoarding past prescriptions).

Pharmaceutical factors

Many elderly pts finds tablets difficult to swallow and the more frail, the more ill, the more dehydrated,
and the more confused they are, the more difficult it becomes. Potassium tablets are quite large and can
cause difficulty. Effervescent potassium tablets have to fizz in water and dissolve, instructions as to their
use are particularly important for the elderly. Counselling as to the use of medicines is important.

Pharmacokinetic factors

Absorption – no examples to show that this is important as a factor specifically in the elderly.

Distribution – important to make adjustments in dosage for body weight when faced with elderly pts
particularly for drugs with a low therapeutic index. There are reductions in plasma protein binding of
some drugs in the elderly for which the decrease is accounted for by the decrease in plasma albumin
with age.

Ageing is associated with loss of lean body mass, and with an increased ratio of fat to muscle and body
water. This enlarges the volume of distribution of fat-soluble drugs, such as diazepam and lidocaine,
whereas the distribution of polar drugs such as digoxinis reduced compared to younger adults. Changes
in plasma proteins also occur with ageing, especially if associated with chronic disease and malnutrition,
with a fall in albumin and a rise in gamma-globulin concentrations.

The distribution of body water and fat is altered in the elderly and because of an increased proportion of
fat lipid-soluble drugs tend to accumulate to a greater extent than in younger patients. It is difficult to
predict what might happen to the volume of distribution of a drug in the elderly, for e.g, the volume of
distribution of diazepam is increased in the elderly but that of nitrazepam is not.

Metabolism - There is a decrease in the hepatic clearance of some but not all drugs with advancing age.
A prolonged plasma half-life (Figure 11.2), can be the result either of reduced clearance or of increased
apparent volume of distribution. Ageing reduces metabolism of some drugs (e.g. benzodiazepines) as
evidenced by reduced hepatic clearance. The reduced clearance of benzodiazepines has important
clinical consequences, as does the long half-life of several active metabolites (Chapter 18). Slow
accumulation may lead to adverse effects whose onset may occur days or weeks after initiating therapy.
Consequently, confusion or memory impairment may be falsely attributed to ageing rather than to
adverse drug effects.

Renal excretion – there is a decrease in glomerular filtration rate with age such that by the age of 80 the
GFR may have fallen to 60 – 70 ml/min. Tubular function also declines with age. Drugs and active
metabolites which are mainly excreted in the urine may therefore require downward adjustment of
dosage, just as they might in renal failure in younger patients, e.g. digoxin, gentamicin and other
aminoglycosides, lithium and procainamide. Some drugs are best avoided in the elderly, for example,
Tetracyclines, which because of poor real function may accumulate, producing nausea and vomiting,
which cause dehydration and further deterioration in renal function.

Pharmacodynamics

 For various reasons, drug sensitivity may be altered in old age

 There appears to be a diminished sensitivity of beta-adrenoceptor function in the elderly, which
decreases the pharmacological efficacy of beta- adrenoceptor agonists and antagonists
 Elderly patients appear to be more sensitive to the anticoagulant effects of warfarin and
generally require smaller dosages to produce adequate anticoagulation
 The elderly brain, particularly where there is hypoxia or fever seems especially sensitive to
centrally- active drugs, e.g hypnotics, sedatives, antidepressants.

Drug interactions

The elderly cerebral circulation does not autoregulate efficiently. Elderly pts easily become
hypovolaemic w/ diuretics (or even without it if ot eating or drinking normally). Peripheral autonomic
responses may be sluggish in response to hypotension. All these factors accumulate to make the
treatment of hypertension in the elderly a matter to be cautious aboutas it is ofte very easy to produce
hypotension, causing syncope, which results in a fall, injury, immobilization, PE. Thus hypotensive
therapy should be viewed with caution.

The elderly are particularly prone to diuretic- induced hypokalemia – prescribe thiazides or loop
diuretics w/ a potassium- sparing diuretic in the elderly, to be on the safe side.