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2 authors, including:
Selvarajan Sandhiya
Jawaharlal Institute of Postgraduate Medical
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Introduction
ife span of humans has increased in the recent years
due to social, economical and health care improvement.
Medical society has identified persons aged over 65 as
elderly while those above 75 as geriatric population. By 2050
the worldwide elderly population is expected to reach 1.4
billion which means that one out of ten people will be more
than 65 years of age. Currently population aging is most
serious in Europe and Japan. China is expected to have an
increase in the proportion of elderly people by next century.
The present elderly population in India is over 77 million,
constituting 7.7% of the total population and is expected
to rise to 100 million by 2013.1
Aging is associated with progressive decline in
physiological functions as well as multiple diseases like
diabetes, hypertension, arthritis and amnesia. These age
related changes associated with reduced income and
loneliness further worsen their health. 2,3 This results in
polypharmacy and increased incidence of adverse drug
reactions (ADRs) as shown in Fig. 1. It has been found that
35% of ambulatory older patients experience an ADR of
which 29% require health care services. Thus 40% health
service expenditure is spent on elderly in developed
countries.4,5 Hence it is mandatory for physicians to be aware
of normal age related physiological and pharmacological
changes taking place in old people. This will help to avoid
irrational prescribing, minimize ADRs and maximize
benefits of drugs in elderly patients. This review deals with
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Table 1 : Age related physiological changes and their consequences on drug therapy in geriatric population.4
System
General
Increased body fat
Vd of lipid soluble drugs is increased requiring higher
Decreased total body water
dose eg. diazepam.
Vd of water soluble drugs is decreased requiring low
dose eg. aminoglycosides, digoxin.
Gastrointestinal tract Decreased gastric acidity
Absorption of basic drugs is enhanced eg. propranolol.
Decreased gastrointestinal motility
Absorption of acidic drugs is decreased eg. barbiturates.
Decreased hepatic and splanchnic Decreased absorption of drugs.
blood flow Decreased metabolism of drugs. eg. lignocaine.
Renal Decreased renal blood flow, glomerular Renal clearance is decreased and hence drugs excreted
filtration rate and tubular secretion
through kidney should be used cautiously eg.
aminoglycosides, digoxin, lithium.
Musculoskeletal Decreased muscle mass Resulting in functional impairment and fracture
Decreased bone density
requiring treatment, hospitalization, etc.
Cardiovascular system
Increased blood pressure Cardiovascular complications requiring treatment,
hospitalization, etc.
Central nervous system
Brain atrophy Results in forgetfulness, depression, Parkinsons,
Decreased brain catecholamine synthesis
insomnia etc. requiring therapy.
Decreased dopaminergic synthesis
Decreased sleep (stage 4)
Genitourinary
Vaginal / urethral mucosal atrophy
Bacteriuria, increased residual urine volume requiring
Prostate enlargement
hormonal or drug therapy.
Endocrine Decreased BMR Resulting in Diabetes mellitus which needs life long
Vulnerable to stress
treatment.
Glucose intolerance
Vd volume of distribution; BMR basal metabolic rate.
Drugs
Absorption Nil
Distribution of
Lipid soluble drugs
Increased
Water soluble drugs Decreased
Acidic drugs
Increased
Basic drugs Decreased
Metabolism
Phase I Decreased
Phase II Nil
Excretion Decreased
Pharmacodynamic changes
The end organ response to a drug is increased in elderly
resulting in toxicity at normal therapeutic doses. The
enhanced sensitivity is seen with commonly used drugs
like NSAIDs, opioids, benzodiazepines, antipsychotics and
antiparkinsonian drugs.4 Some of the commonly used drugs
and their adverse effects in elderly patients are shown in
Table 3. Hence care should be taken to reduce the dose while
prescribing these drugs in elderly. Since, pharmacokinetic
changes are more important than pharmacodynamic
changes while deciding the treatment, this review gives
more details about these parameters.
Pharmacokinetic changes
Absorption
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Table 4 : Some of the inappropriate drugs to be avoided in elderly according to Beers criteria26
Drugs Statement
1. Sedative - hypnotics
a. Long acting benzodiazepines eg. Chlordiazepoxide, diazepam, flurazepam
All drugs should be avoided
b. Short acting benzodiazepines eg. oxazepam, triazolam, alprazolam Night use > 4 wks to be avoided
c. Short acting barbiturates eg. Pentobarbital, secobarbital
All use should be avoided
2. Antidepressants : Amitriptyline
All use should be avoided
3. Antipsychotics
Haloperidol Doses > 3 mg/d should be avoided;
patients with known psychotic disorders may
require higher doses
Thioridazine Doses > 30 mg/day should be avoided
4. Antihypertensives
Hydrochlorothiazide Doses > 50 mg/day should be avoided
Propranolol
All use should be avoided except if used to
control violent behaviours
5. NSAIDs : Indomethacin, phenylbutazone
All use should be avoided
6. Analgesics : Propoxyphene, Pentazocine
All use should be avoided
7. Dementia treatment : Cyclandelate, Isoxsuprine
All use should be avoided
8. Platelet inhibitors : Dipyridamole
All use should be avoided
9. Histamine blockers : Ranitidine Doses > 300 mg/day and therapy beyond 12
wks should be avoided
10. Antibiotics : Oral antibiotics Therapy > 4 wks should be avoided except for
osteomyelitis, prostatitis, tuberculosis,
endocarditis
11. Decongestants : Oxymetazoline, phenylephrine, pseudoephedrine Daily use for > 2wks should be avoided
12. Iron Doses > 325 mg/day should be avoided
13. Muscle relaxants : Carisoprodol
All use should be avoided
14. GI antispasmodics : Dicyclomine
All use should be avoided
GI - gastrointestinal; NSAIDs Non steroidal anti inflammatory drugs
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Adherence
Cognitive changes like forgetting to take pills at the
right time, economic stresses due to decreased income,
increased expenses due to illness, loss of spouse, physical
disabilities etc can reduce adherence in elderly people. This
can be improved by reducing the number and frequency
of drug administration as it is easy to remember. Dosage
schedule at night time is preferred for antipsychotic drugs to
reduce adverse reactions like drowsiness, sedation, postural
hypotension, etc. Similarly, diuretics are to be prescribed in
the morning time as they may disturb sleep given during
night time. Further drugs packed in readily openable
containers and labeled in large print are needed for elderly
patients with arthritis and poor vision. Big size tablets and
capsules should be avoided as elderly patients may have
difficulty in swallowing. Effervescent tablets and liquid
formulations like syrups are preferred in old people. If many
drugs are to be used together they should have distinct
colour and shape to avoid confusion to the patient.4
Above all educating the elderly patients regarding the
use and administration of drugs and the importance of
drugs to their well being is necessary to improve adherence.
It is also essential to discuss these things with a close
relative, friend, neighbour or any other care giver. Moreover
to be vigilant patients or their relatives should be asked to
bring the drug containers during follow up visits. If the drug
is found to be outdated or not needed in the future it can
be discarded after clearly explaining to the patient.4
Difficulties in setting therapeutic guidelines
for elderly patients
Since the elderly population is on the rise, understanding
age related physiological and pharmacological changes,
avoiding polypharmacy and regular review of all drug
treatment will help in rational prescription. Setting
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Summary
Drug therapy in older patients varies from that of adults
due to altered physiological functions, associated illness,
age related disability, loneliness and stress. The success of
a drug therapy in elderly, depends on considering these
factors in addition to correct diagnosis, treatment plan,
prescription, patient education and dose adherence.
Care should be taken to avoid iatrogenic diseases in this
population by avoiding inappropriate prescribing. For
appropriate and rational prescription in elderly patients the
following factors should be taken into account
age related pharmacokinetic and pharmacodynamic
changes
socioeconomic, cultural and psychological factors
multiple diseases and altered presentation of illness
decreased vision, cognitive and hearing impairment
polypharmacy and increased susceptibility to ADRs
Above all adding quality life to years should be the major
concern of a physician than mere addition of years to life.
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