Drug Therapy in Elderly
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Drug therapy in elderly
Article in The Journal of the Association of Physicians of India · August 2008
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Drug Therapy in Elderly
S Sandhiya*, C Adithan**
Abstract
Population aging is considered as the most serious problem in developed countries and is going to be a threat for
developing countries. Aging is associated with various physiological changes and multiple diseases like diabetes,
hypertension, arthritis etc. which alter the pharmacological response to a drug. Moreover, elderly people are more
sensitive to frequently used drugs like NSAIDs, benzodiazepines, opioids etc. All these factors alter the drug response
resulting in adverse drug reactions (ADRs) and hospitalization, consuming 40% of health service expenditure in
developed countries. 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. Above all educating the old patients and their care providers
regarding the importance and proper use of drugs to their well being is necessary to improve adherence. Hence
setting therapeutic guidelines for treating elderly patients will enhance their quality of life. ©
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
L
*Senior Resident; **Director - Professor and Head; Department of
Pharmacology, JIPMER, Puducherry - 605 006, India.
© JAPI • VOL. 56 • JULY 2008
Fig. 1 : Factors causing ADR in elderly.
the age related alterations in pharmacological response,
precautions to be taken to avoid ADRs and principles of
prescribing drugs for elderly patients.
Pharmacological changes in elderly
Age related physiological and pathological changes play
a major role in altering the pharmacological actions of a
drug. The age related physiological alterations in various
organs and their consequences are shown in Table 1 and
2. Of these changes impaired hepatic and renal functions
play a significant role in decreasing absorption, distribution,
metabolism and excretion of drugs. These pharmacokinetic
changes alter free drug concentration which is a major
determinant of a drug’s potency and duration of action.
Apart from these changes, aging is also associated with
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525
Table 1 : Age related physiological changes and their consequences on drug therapy in geriatric population.4
System
Age related physiological changes Consequences
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, Parkinson’s,
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.
Table 2 : Age related pharmacokinetic changes in the elderly.4
Pharmacokinetic parameter
Age related changes
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 like altered organ response
to drugs. These changes are vital as they contribute to the
variations in drug response.4
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 3 : Commonly used drugs and their adverse effects in
elderly.4
Adverse effects
First generation antihistamines
Promethazine, Strong anticholinergic and
Hydroxyzine
sedative effect.
Low potent antipsychotics
Chlorpromazine Strong anticholinergic and
sedative effect.
Prochlorperazine
Extrapyramidal and orthostatic
adverse events.
Long acting benzodiazepines
Nitrazepam
Long half – life resulting in
prolonged sedation,
Flunitrazepam
causing falls and fractures.
Analgesics
Pethidine Causes convulsions and renal
failure.
Propoxyphene
Combination of NSAID with
Warfarin
Increases GI bleeding.
ACE inhibitor Renal failure.
SSRI
Increases GI bleeding.
Diuretics Reduces the effect of diuretics.
ACE- angiotensin converting enzyme; SSRI – selective serotonin
reuptake inhibitor
Oral absorption of drug is altered in elderly due to
fall in gastric pH, delayed gastric emptying, reduced
gastrointestinal (GI) blood flow and motility. The
consequences of these changes are shown in Table 1 and 2.
However, absorption of a drug does not change significantly
with age as other pharmacokinetic parameters.4
Distribution
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© JAPI • VOL. 56 • JULY 2008
Drug distribution in the body depends on body
composition, plasma protein binding and blood flow to
the organs. Aging is associated with reduced total body
water and increase in total body fat. This physiological
change results in decreased volume of distribution (Vd)
of water soluble drugs like digoxin (Table 2). Thus elderly
patients with congestive heart failure require lesser
loading and maintenance doses of digoxin. Volume of
distribution (Vd) of lipid soluble drugs like diazepam and
nitrazepam is increased and hence the dose needs to be
increased. However, lorazepam is an exception among the
benzodiazepines as it has small volume of distribution.4-7
One of the important determinants of Vd is relative binding
of drugs to plasma proteins like albumin and α1 – acid
glycoprotein. With aging, the concentration of albumin
which binds to acidic drugs decreases. This is especially
important for drugs like phenytoin with high albumin
binding. In a patient with normal renal function, 92% of
phenytoin is bound to plasma protein and only 8% is in free
form. This free form increases to 16% in renal impairment
thus producing ADRs.8 However, α1 – acid glycoprotein
which binds to basic drugs increases with aging and
binding of basic drugs like antidepressants, antipsychotics,
β blockers, increase resulting in decreased free drug level
and reduced action. Hence, theoretically speaking the dose
of acidic drugs like phenytoin and barbiturates needs to
be decreased as the free form available for action is more
resulting in toxicity. Similarly the dose of basic drugs like β
blockers should be increased as the free form of the drug
is less resulting in therapeutic failure (Table 2). Surprisingly,
clinically significant change with alteration in plasma
protein binding has not been reported so far.
Metabolism
Age related attenuation of liver functions due to reduced
hepatic mass and blood flow decreases drug metabolizing
capacity. This has been proved with a compound called
antipyrine, which is totally metabolized by hepatic
enzymes. In elderly people antipyrine shows prolonged
half – life and decreased metabolic clearance, implying
reduced metabolizing capacity of liver.9,10 Altered drug
metabolism can also be attributed to other factors like
co-administration of drugs, associated illness, smoking,
genetic factors and environmental factors.11 Drugs undergo
two types of metabolism in the liver namely phase I which
includes reactions like oxidation, hydroxylation etc and
phase II mainly involving conjugation reactions. The main
purpose of these phases is to make the drug water soluble
and eliminate it from the body. Drugs like chlordiazepoxide
and diazepam which undergo oxidative metabolism (Phase
I) exhibit decreased clearance and increased half – life in
elderly patients. While drugs like oxazepam, lorazepam and
temazepam which are eliminated by conjugation (Phase II)
reactions do not show alteration in clearance.12 This clearly
shows that only phase I metabolism is affected in the elderly
without significant change in phase II metabolism.
Excretion
© JAPI • VOL. 56 • JULY 2008
The most important age related change is reduced renal
clearance seen in about two thirds of elderly patients.13,14
Drugs that are mainly excreted via kidney have a prolonged
half – life in patients with reduced renal function resulting
in drug toxicity at therapeutic doses. However, the decrease
in renal function as measured by creatinine clearance is not
associated with an equal rise in serum creatinine level. This
may be a consequence of declined muscle mass with age.
Hence a rough correction can be made by using Cockcroft
– Gault formula13,15 which is applicable to patients between
40- 80 yrs of age.
Cockcroft – Gault formula:
CLCr (ml/min) =
(140 – age in yrs) x weight in kg
72 x serum creatinine in mg/dl
This is a population estimate and hence may not be
applicable to a particular patient. In one third of the elderly
with normal renal functions, a dose correction based on
this formula will be too low. However, a low initial dose is
desirable if the physician is not sure of the patient‘s renal
status. Moreover, dose reduction is mandatory only for drugs
or their active metabolites which are excreted primarily
through kidney. For example the usual maintenance dose
of digoxin in normal elderly patient is 125 µg while in renal
failure it has to be reduced to 62.5 µg.
Nomogram is another approach for evaluation of
endogenous – creatinine clearance from age, body weight
and serum creatinine. This helps in determining the dose
and dosing interval of drugs like aminoglycosides and
vancomycin which are mainly excreted through kidney in
elderly with impaired renal function.16-18 In the schematic
nomogram shown in Fig. 2, the right hand ordinate indicates
the elimination clearance of drug measured in young adults
of normal renal function and left hand ordinate indicates
expected elimination clearance of drug in a functionally
anephric patient assuming that some of administered
dose is eliminated by non renal routes. The dotted line
connecting these points from the creatinine clearance in
abcissa can be used to estimate drug elimination clearance
in an individual patient.
Adverse drug reactions in the elderly
Drug related adverse effects have profound economic
consequences on elderly patients as well as on health
care system. Thirty percent of hospital admissions in
elderly people are drug related problems like depression,
constipation, falls, immobility, confusion and hip fracture.5,19
ADRs are considered the fourth leading cause of death in
United States next to heart disease, cancer and stroke.20
However, the incidence is underestimated as adverse drug
reactions mimic disease states and are less likely recognized
by physicians and elderly patients themselves.21
Adverse reactions occurring in the elderly may be a
result of intrinsic or extrinsic factors. Intrinsic factors are
mainly patient related and include age related physiological
changes, altered pharmacological parameters, impaired
organ functions, female sex, drug interactions, small body
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527
size, severity of the disease, presence of multiple diseases
and polypharmacy. Extrinsic factors are physician related
and depends on prescribing pattern and medication
management.
Drug usage and frequency of ADR in the elderly
ADR in old people depends on the number of diseases
and the drugs used to treat them. More the number of
drugs prescribed higher the chance of drug interactions
and adverse drug reactions. Approximately 40 percent
of elderly people use at least five medications per week
and 12 percent use minimum ten medications per week.20
Positive relationship has been found between number of
drugs taken and the incidence of adverse reactions. Studies
have shown that 85-95 % of ambulatory elderly take at
least one medication with an average of three to four.2223
Drugs commonly associated with ADRs are sedatives,
antihypertensives, antiparkinsonian, antipsychotics,
Fig. 2 : Schematic diagram showing estimation of individual drug
clearance using a nomogram.
Endogenous creatinine clearance (CLCr) either calculated or measured
can be used to find out the individual patient’s drug clearance. This
information can be used to adjust dose and dosing interval.
NSAIDS, steroids and theophylline.24,25 Hence, a complete
drug history including over the counter medications is
mandatory prior to prescribing.
In the absence of precise clinical information, consensus
criteria can be used for safe prescribing in elderly patients.
One of the most widely used consensus criteria for drug
use in elderly patients was proposed by Beers et al in
1991.26,27 This criteria educates clinicians regarding the
drugs or classes of drugs to be avoided in elderly in
nursing home as shown in Table 4. These drugs were either
lacking in efficacy or pose high risk to patients while safer
alternatives are available. In 1997, the criteria were updated
and applied to all elderly patients.27 The Beer’s criteria for
ambulatory and nursing populations older than 65 years
had been revised and updated again in 2002.28 Some of
the drugs to be avoided in elderly people according to
Beers criteria are given in Table 4. Beer’s criteria should be
viewed as an important component of the clinical decision
– making process to ensure best possible outcomes for
elderly patients.29 However, aging and drug therapy are
individualized process, hence patient specific parameters
must be given preference while prescribing.
Precautions to be taken in elderly people to avoid adverse
drug reactions:
1. Ensure that the symptom deserving medical treatment
is not an adverse effect of another drug.
2. Drug therapy should be considered only if nonpharmacologic measure fails or if benefit outweighs
risk.
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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© JAPI • VOL. 56 • JULY 2008
3. Number of drugs and dosage form should be kept as
convenient as possible.
4. Potential drug interactions should be weighed before
including a new drug in the regimen.
Treatment options for some commonly seen
diseases
Insomnia
The prevalence of sleep disorders increases with age.
Older people tend to sleep earlier in the evening but also
wake up earlier. Some of them have fragmented sleep due
to repeated awakenings. This may be primary or secondary
to coexistent illness or medications. Pain due to arthritis
constitutes one of the most common causes of insomnia
in this population. Similarly nocturia due to diabetes or
prostatic disease is also a cause of sleep disturbances
and daytime fatigue. In these cases, treatment should
be targeted at the underlying disease to improve sleep
efficiency and unnecessary use of hypnotics should be
avoided. Moreover, simple measures like avoidance of
beverages in the night, voiding the bladder before going to
bed and shifting to a dark, quiet room may help the patient
in getting sleep.
However, if treatment for insomnia is needed, sedative –
hypnotics like benzodiazepines can be used. Care should be
taken to avoid long acting drugs like diazepam, flurazepam
and chlordiazepoxide as they cause drowsiness, confusion,
slurred speech, unsteady gait, falls and day time sleep. These
effects seem to be less with short acting benzodiazepines
like triazolam and oxazepam which may be effective for
sleep onset problems.16,26 In patients with early-morning
awakening, an intermediate agent such as temazepam
may be more useful. Similarly non-benzodiazepine drugs
like zolpidem, zaleplon, zopiclone and eszopiclone which
have little disruption on normal sleep architecture can also
be used.30
Arthritis
NSAIDs like aspirin are frequently prescribed in elderly
for diseases like rheumatoid arthritis, osteoarthritis, etc. GI
bleeding associated with such treatment is more common
in elderly patients. Selective COX-2 inhibitors seemed
to be promising candidates for long-term treatment
of chronic diseases, like arthritis due to their reduced
incidence of gastrointestinal adverse effects. However,
some of these agents have been withdrawn due to their
side effects like myocardial infarction and stroke. Hence,
non pharmacological measures like weight reduction,
warmth, exercise, use of a walking stick, etc. should be
tried first for diseases like osteoarthritis, rheumatoid
arthritis, soft tissue lesions and back pain. In case of pain,
analgesics like paracetamol or ibuprofen can be used.
If pain relief is inadequate with either drug an opioid
analgesic can be added.16 According to the Working Group
on Pain Management, an international multidisciplinary
panel, paracetamol is considered as baseline drug for the
© JAPI • VOL. 56 • JULY 2008
treatment of moderate-to-severe musculoskeletal pain
and for greater analgesia addition of a weak opioid is
recommended.31,32
Edema
Mild oedema can be treated by non-pharmacological
measures like elevation of legs, supportive stockings and
active life style. If treatment with diuretics is needed it has to
be restricted for fewer days. Diuretics prescribed irrationally
for a longer duration may lead to postural hypotension
and falls.16
Other drugs
Drug induced bleeding is commonly seen in elderly
and hence drugs like co-trimoxazole should be avoided
unless there is no other alternative. Similarly the dose of
anticoagulant like warfarin needs to be decreased as it
causes serious bleeding in them.16 Moreover neuroprotective
agents used in elderly people for stroke have not shown any
beneficial effects in the long run. Hence by avoiding these
drugs adherence can be improved.
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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529
objectives and guidelines may reduce unwanted adverse
reactions due to inappropriate or over prescribing in elderly
patients (Fig. 3). Some of the following points can be taken
into account to reduce ADRs.
a. Need for the treatment
Non pharmacological measures should be considered
as far as possible before starting treatment for diseases like
obesity, mild hypertension and atherosclerosis. They can be
controlled by altered life style, regular walking, reduced salt
intake, cessation of smoking and alcohol consumption.
b. Choosing the appropriate drug
If the patient needs treatment, most efficacious drug
with less ADR targeting the cause than symptom should
be selected. The associated illness like renal failure, hepatic
failure, cardiac failure, diabetes mellitus and hypertension
should be also be taken into consideration. Avoiding drugs
like â blockers in hypertensive patients with history of
asthma or reducing dose of digoxin in elderly with renal
failure can prevent unwanted ADR induced diseases.
c. Formulation
Prescribing drugs in the form of syrups, suspensions and
effervescent tablets can improve adherence in elderly as
they find it easy to swallow. Similarly care should be taken
not to give drugs in child-resistant containers as patients
with debilitating diseases may find it difficult to open.
d. Maintaining record and periodic review
Maintaining a drug record will help to check adherence,
possible drug interactions, ADR and the economic burden
of the patient. Patients receiving long term therapy should
be reviewed carefully to assess the need for the drug.
Depending on the disease condition the drug can be either
stopped or changed.
Difficulties in setting guidelines
Older generation represent a high proportion of the
population receiving drugs like NSAIDs for rheumatoid
arthritis and osteoarthritis.33 Moreover, 80% of deaths due to
acute myocardial infarction occur in people above 65 yrs of
age.34,35 Hence drugs used for these conditions will provide
information regarding ADRs only if used in this population.
However, for safety concern this special population is
usually not involved in clinical trials. This limits the ability
to generalize study findings in the elderly population
which experiences multiple diseases.36,37 Of these, diseases
like diabetes mellitus and hypertension are chronic and
are not always effectively treated with drugs. Moreover,
physiological changes and the resulting pharmacokinetic
variations differ among elderly individuals. These factors
make therapeutic decision making or setting guidelines for
an individual elderly patient more complex.
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.
REFERENCES
Fig. 3 : Principles of prescribing in elderly.4,16
530
1. Shah Naseem. Oral health care system for elderly in India. Geriatrics
and Gerontology International 2004;4:S162-64.
2. Joshi K , Kumar R, Avasthi A. Morbidity profile and its
relationship with disability and psychological distress among
elderly people in Northern India. Int J Epidemiol 2003;32:
978-87.
3. Taqui AM, Itrat A, Qidwai W, Qadri Z. Depression in the elderly: does
family system play a role? A cross-sectional study. BMC Psychiatry
2007;7:57.
4. Cusack BJ, Neilson CP, Vestal RE. Geriatric Clinical Pharmacology and
Therapeutics. In: Speight TM, Holford NHG, editors. Avery’s Drug
Treatment. Adis press Ltd., Auckland 1987;174-223.
5. Hanlon JT, Schmader KE, Kornkowski MJ, Weinberge M, Landsman PB,
Samsa GP, et al. Adverse drug events in high risk older outpatients. J
Am Geriatric Soc 1997;45:945-48.
6. Glass J, Lanctot KL, Herrmann N, Sproule BA, Busto UE. Sedative
hypnotics in older people with insomnia: meta-analysis of risks and
benefits. Br Med J 2005;331:1169.
7. Hemmelgarn B, Suissa S, Huang A, Boivin JF, Pinard G. Benzodiazepine
use and the risk of motor vehicle crash in the elderly. JAMA
1997;278:27-31.
8. Atkinson AJ. Effects of renal disease on pharmacokinetics. In:
www.japi.org
© JAPI • VOL. 56 • JULY 2008
Atkinson AJ, Daniels CE, Dedrick RL, Grudzinkas CV, Markey SP,
editors. Principles of Clinical Pharmacology. Academic Press, New
York 2001:43-9.
9. Wood AJ, Vestal RE, Wilkinson GR, Branch RA, Shand DG.
Effect of aging and cigarette smoking on antipyrine and
indocyanine green elimination. Clin Pharmacol Ther 1979; 26:
16-20.
10. Wynne HA, Cope LH, Mutch E, Rawlins MD, Woodhouse KW, James
OF. The effect of age upon liver volume and apparent liver blood flow
in healthy man. Hepatology 1989; 9:297-301.
11. Farah F, Taylor W, Rawlins MD, James O. Hepatic drug acetylation and
oxidation: effects of aging in man. Br Med J 1977; 2:155-6.
12. Bellantuono C, Reggi V, Tognoni G, Garattini S. Benzodiazepines:
clinical pharmacology and therapeutic use. Drugs 1980; 19:195219.
13. B e r t r a m G K a t z u n g . S p e c i a l a s p e c t s o f g e r i a t r i c
pharmacology. In: Bertram G Katzung, editor. Basic and
C l i n i c a l Ph a r m a co l o g y. M c G raw H i l l, N e w Yo r k 2 0 0 7 :
983-90.
14. Rowe JW, Andres R, Tobin JD, Norris AH, Shock NW. The effect of age
on creatinine clearance in men: a cross-sectional and longitudinal
study. J Gerontol 1976;31:155-63.
15. Cockcroft DW, Gault MH. Prediction of creatinine clearance from
serum creatinine. Nephron 1976; 16:31-41.
16. British National Formulary. BMJ and RPS Publishing, UK 2006:18-9.
17. Neilsen KS, Hansen JM, Kampmann J, Kristensen M. Rapid evaluation
of creativine clearance. Lancet 1971;1:1133-4.
18. Maeda Y, Omoda K, Fukuhara S, Ohta M, Ishii Y, Murkami
T. Evaluation of clinical efficacy of Maeda’s nomogram for
vancomycin dosage adjustment in adult Japanese MRSA
pneumonia patients. Drug Metab Pharmacokinet 2006;21:
54-60.
19. Bootman JL, Harrison DL, Cox E. The health care cost of drug –related
morbidity and mortality in nursing facilities. Arch Intern Med
1997;157:2089-96.
20. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug
reactions in hospitalized patients: a meta-analysis of prospective
studies. JAMA 1998;279:1200-05.
21. Nolan L, O’Malley K. Prescribing for the elderly. Part 1. Sensitivity
of the elderly to adverse drug reactions. J Am Geriatric Soc
1988;36:142-9.
22. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent
patterns of medication use in the ambulatory adult population of the
United States: the Slone survey. JAMA 2002;287:337-44.
23. Pham CB, Dickman RL. Minimising adverse drug events in older
patients. Am Fam Physician 2007;76:1837-44.
24. Grymonpre RE, Mitenko PA, Sitar DS, Aoki FY, Montgomery PR.
Drug - associated hospital admissions in older mental patients. J Am
Geriatric Soc 1988;36:1092-8.
25. Klein LE, German PS, Levine DM, Feroli ER, Ardery J. Medication
problems among outpatients. A study with emphasis on the elderly.
Arch Intern Med 1984;144:1185-8.
26. Beers MH, Ouslander JG, Rollinger J, Reuben DB, Beck JC.
Explicit criteria for determining inappropriate medication
use in nursing home residents. Arch Intern Med 1991;151:
1825-32.
27. Beers MH. Explicit criteria for determining potentially inappropriate
medication use by the elderly. Arch Intern Med 1997;157:1531-36.
28. Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH.
Updating the Beers criteria for potentially inappropriate medication
use in older adults: results of a US consensus panel of experts. Arch
Intern Med 2003;163:2716-24.
29. Avorn J, Gurwitz JH, Rochon P. Principles of Pharmacology.In: Cassel
CK, Leipzig RM, Cohen HJ, Larson EB, Meier DE, editors. Geriatric
Medicine, an evidence based approach. Springer, New York 2003:6581.
30. Wolkove N, Elkholy O, Baltzan M, Palayew M. Sleep and aging: 1. Sleep
© JAPI • VOL. 56 • JULY 2008
disorders commonly found in older people. CMAJ 2007;176:1299304.
31. S chnitzer TJ. Update on guidelines for the treatment
of chronic musculoskeletal pain. Clin Rheumatol 2006;25:
S22-9.
32. Straand J, Fetveit A, Rognstad S, Gjelstad S, Brekke M, Dalen I. A
cluster-randomized educational intervention to reduce inappropriate
prescription patterns for elderly patients in general practice—The
Prescription Peer Academic Detailing (Rx-PAD) study [NCT00281450].
BMC Health Serv Res 2006;6:72.
33. Hogan DB, Campbell NR, Crutcher R, Jennett, MacLeod N. Prescription
of nonsteroidal anti-inflammatory drugs for elderly people in Alberta.
CMAJ 1994;151:315–22.
34. Barone-Adesi F, Vizzini L, Merletti F, Richiardi L. Short-term effects of
Italian smoking regulation on rates of hospital admission for acute
myocardial infarction. Eur Heart J 2006;27:2468-72.
35. Singla I, Hreybe H, Saba S. Risk of death and recurrent ventricular
arrhythmias in survivors of cardiac arrest concurrent with acute
myocardial infarction. Indian Pacing Electrophysiol J 2008;8:5-13.
36. Lee PY, Alexander KP, Hammill BG, Pasquali SK, Peterson ED.
Representation of elderly persons and women in published
randomized trials of acute coronary syndromes. JAMA 2001;286:70813.
37. Rochon PA, Fortin PR, Dear KB, Minaker KL, Chalmers TC. Reporting of
age data in clinical trials of arthritis. Deficiencies and solutions. Arch
Intern Med 1993;153:243-8.
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Drug therapy in elderly
Article in The Journal of the Association of Physicians of India · August 2008
Source: PubMed
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Selvarajan Sandhiya
Jawaharlal Institute of Postgraduate Medical…
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Update Article
Drug Therapy in Elderly
S Sandhiya*, C Adithan**
Abstract
Population aging is considered as the most serious problem in developed countries and is going to be a threat for
developing countries. Aging is associated with various physiological changes and multiple diseases like diabetes,
hypertension, arthritis etc. which alter the pharmacological response to a drug. Moreover, elderly people are more
sensitive to frequently used drugs like NSAIDs, benzodiazepines, opioids etc. All these factors alter the drug response
resulting in adverse drug reactions (ADRs) and hospitalization, consuming 40% of health service expenditure in
developed countries. 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. Above all educating the old patients and their care providers
regarding the importance and proper use of drugs to their well being is necessary to improve adherence. Hence
setting therapeutic guidelines for treating elderly patients will enhance their quality of life. ©
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
L
*Senior Resident; **Director - Professor and Head; Department of
Pharmacology, JIPMER, Puducherry - 605 006, India.
© JAPI • VOL. 56 • JULY 2008
Fig. 1 : Factors causing ADR in elderly.
the age related alterations in pharmacological response,
precautions to be taken to avoid ADRs and principles of
prescribing drugs for elderly patients.
Pharmacological changes in elderly
Age related physiological and pathological changes play
a major role in altering the pharmacological actions of a
drug. The age related physiological alterations in various
organs and their consequences are shown in Table 1 and
2. Of these changes impaired hepatic and renal functions
play a significant role in decreasing absorption, distribution,
metabolism and excretion of drugs. These pharmacokinetic
changes alter free drug concentration which is a major
determinant of a drug’s potency and duration of action.
Apart from these changes, aging is also associated with
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525
Table 1 : Age related physiological changes and their consequences on drug therapy in geriatric population.4
System
Age related physiological changes Consequences
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, Parkinson’s,
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.
Table 2 : Age related pharmacokinetic changes in the elderly.4
Pharmacokinetic parameter
Age related changes
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 like altered organ response
to drugs. These changes are vital as they contribute to the
variations in drug response.4
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
526
Table 3 : Commonly used drugs and their adverse effects in
elderly.4
Adverse effects
First generation antihistamines
Promethazine, Strong anticholinergic and
Hydroxyzine
sedative effect.
Low potent antipsychotics
Chlorpromazine Strong anticholinergic and
sedative effect.
Prochlorperazine
Extrapyramidal and orthostatic
adverse events.
Long acting benzodiazepines
Nitrazepam
Long half – life resulting in
prolonged sedation,
Flunitrazepam
causing falls and fractures.
Analgesics
Pethidine Causes convulsions and renal
failure.
Propoxyphene
Combination of NSAID with
Warfarin
Increases GI bleeding.
ACE inhibitor Renal failure.
SSRI
Increases GI bleeding.
Diuretics Reduces the effect of diuretics.
ACE- angiotensin converting enzyme; SSRI – selective serotonin
reuptake inhibitor
Oral absorption of drug is altered in elderly due to
fall in gastric pH, delayed gastric emptying, reduced
gastrointestinal (GI) blood flow and motility. The
consequences of these changes are shown in Table 1 and 2.
However, absorption of a drug does not change significantly
with age as other pharmacokinetic parameters.4
Distribution
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© JAPI • VOL. 56 • JULY 2008
Drug distribution in the body depends on body
composition, plasma protein binding and blood flow to
the organs. Aging is associated with reduced total body
water and increase in total body fat. This physiological
change results in decreased volume of distribution (Vd)
of water soluble drugs like digoxin (Table 2). Thus elderly
patients with congestive heart failure require lesser
loading and maintenance doses of digoxin. Volume of
distribution (Vd) of lipid soluble drugs like diazepam and
nitrazepam is increased and hence the dose needs to be
increased. However, lorazepam is an exception among the
benzodiazepines as it has small volume of distribution.4-7
One of the important determinants of Vd is relative binding
of drugs to plasma proteins like albumin and α1 – acid
glycoprotein. With aging, the concentration of albumin
which binds to acidic drugs decreases. This is especially
important for drugs like phenytoin with high albumin
binding. In a patient with normal renal function, 92% of
phenytoin is bound to plasma protein and only 8% is in free
form. This free form increases to 16% in renal impairment
thus producing ADRs.8 However, α1 – acid glycoprotein
which binds to basic drugs increases with aging and
binding of basic drugs like antidepressants, antipsychotics,
β blockers, increase resulting in decreased free drug level
and reduced action. Hence, theoretically speaking the dose
of acidic drugs like phenytoin and barbiturates needs to
be decreased as the free form available for action is more
resulting in toxicity. Similarly the dose of basic drugs like β
blockers should be increased as the free form of the drug
is less resulting in therapeutic failure (Table 2). Surprisingly,
clinically significant change with alteration in plasma
protein binding has not been reported so far.
Metabolism
Age related attenuation of liver functions due to reduced
hepatic mass and blood flow decreases drug metabolizing
capacity. This has been proved with a compound called
antipyrine, which is totally metabolized by hepatic
enzymes. In elderly people antipyrine shows prolonged
half – life and decreased metabolic clearance, implying
reduced metabolizing capacity of liver.9,10 Altered drug
metabolism can also be attributed to other factors like
co-administration of drugs, associated illness, smoking,
genetic factors and environmental factors.11 Drugs undergo
two types of metabolism in the liver namely phase I which
includes reactions like oxidation, hydroxylation etc and
phase II mainly involving conjugation reactions. The main
purpose of these phases is to make the drug water soluble
and eliminate it from the body. Drugs like chlordiazepoxide
and diazepam which undergo oxidative metabolism (Phase
I) exhibit decreased clearance and increased half – life in
elderly patients. While drugs like oxazepam, lorazepam and
temazepam which are eliminated by conjugation (Phase II)
reactions do not show alteration in clearance.12 This clearly
shows that only phase I metabolism is affected in the elderly
without significant change in phase II metabolism.
Excretion
© JAPI • VOL. 56 • JULY 2008
The most important age related change is reduced renal
clearance seen in about two thirds of elderly patients.13,14
Drugs that are mainly excreted via kidney have a prolonged
half – life in patients with reduced renal function resulting
in drug toxicity at therapeutic doses. However, the decrease
in renal function as measured by creatinine clearance is not
associated with an equal rise in serum creatinine level. This
may be a consequence of declined muscle mass with age.
Hence a rough correction can be made by using Cockcroft
– Gault formula13,15 which is applicable to patients between
40- 80 yrs of age.
Cockcroft – Gault formula:
CLCr (ml/min) =
(140 – age in yrs) x weight in kg
72 x serum creatinine in mg/dl
This is a population estimate and hence may not be
applicable to a particular patient. In one third of the elderly
with normal renal functions, a dose correction based on
this formula will be too low. However, a low initial dose is
desirable if the physician is not sure of the patient‘s renal
status. Moreover, dose reduction is mandatory only for drugs
or their active metabolites which are excreted primarily
through kidney. For example the usual maintenance dose
of digoxin in normal elderly patient is 125 µg while in renal
failure it has to be reduced to 62.5 µg.
Nomogram is another approach for evaluation of
endogenous – creatinine clearance from age, body weight
and serum creatinine. This helps in determining the dose
and dosing interval of drugs like aminoglycosides and
vancomycin which are mainly excreted through kidney in
elderly with impaired renal function.16-18 In the schematic
nomogram shown in Fig. 2, the right hand ordinate indicates
the elimination clearance of drug measured in young adults
of normal renal function and left hand ordinate indicates
expected elimination clearance of drug in a functionally
anephric patient assuming that some of administered
dose is eliminated by non renal routes. The dotted line
connecting these points from the creatinine clearance in
abcissa can be used to estimate drug elimination clearance
in an individual patient.
Adverse drug reactions in the elderly
Drug related adverse effects have profound economic
consequences on elderly patients as well as on health
care system. Thirty percent of hospital admissions in
elderly people are drug related problems like depression,
constipation, falls, immobility, confusion and hip fracture.5,19
ADRs are considered the fourth leading cause of death in
United States next to heart disease, cancer and stroke.20
However, the incidence is underestimated as adverse drug
reactions mimic disease states and are less likely recognized
by physicians and elderly patients themselves.21
Adverse reactions occurring in the elderly may be a
result of intrinsic or extrinsic factors. Intrinsic factors are
mainly patient related and include age related physiological
changes, altered pharmacological parameters, impaired
organ functions, female sex, drug interactions, small body
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527
size, severity of the disease, presence of multiple diseases
and polypharmacy. Extrinsic factors are physician related
and depends on prescribing pattern and medication
management.
Drug usage and frequency of ADR in the elderly
ADR in old people depends on the number of diseases
and the drugs used to treat them. More the number of
drugs prescribed higher the chance of drug interactions
and adverse drug reactions. Approximately 40 percent
of elderly people use at least five medications per week
and 12 percent use minimum ten medications per week.20
Positive relationship has been found between number of
drugs taken and the incidence of adverse reactions. Studies
have shown that 85-95 % of ambulatory elderly take at
least one medication with an average of three to four.2223
Drugs commonly associated with ADRs are sedatives,
antihypertensives, antiparkinsonian, antipsychotics,
Fig. 2 : Schematic diagram showing estimation of individual drug
clearance using a nomogram.
Endogenous creatinine clearance (CLCr) either calculated or measured
can be used to find out the individual patient’s drug clearance. This
information can be used to adjust dose and dosing interval.
NSAIDS, steroids and theophylline.24,25 Hence, a complete
drug history including over the counter medications is
mandatory prior to prescribing.
In the absence of precise clinical information, consensus
criteria can be used for safe prescribing in elderly patients.
One of the most widely used consensus criteria for drug
use in elderly patients was proposed by Beers et al in
1991.26,27 This criteria educates clinicians regarding the
drugs or classes of drugs to be avoided in elderly in
nursing home as shown in Table 4. These drugs were either
lacking in efficacy or pose high risk to patients while safer
alternatives are available. In 1997, the criteria were updated
and applied to all elderly patients.27 The Beer’s criteria for
ambulatory and nursing populations older than 65 years
had been revised and updated again in 2002.28 Some of
the drugs to be avoided in elderly people according to
Beers criteria are given in Table 4. Beer’s criteria should be
viewed as an important component of the clinical decision
– making process to ensure best possible outcomes for
elderly patients.29 However, aging and drug therapy are
individualized process, hence patient specific parameters
must be given preference while prescribing.
Precautions to be taken in elderly people to avoid adverse
drug reactions:
1. Ensure that the symptom deserving medical treatment
is not an adverse effect of another drug.
2. Drug therapy should be considered only if nonpharmacologic measure fails or if benefit outweighs
risk.
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
528
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© JAPI • VOL. 56 • JULY 2008
3. Number of drugs and dosage form should be kept as
convenient as possible.
4. Potential drug interactions should be weighed before
including a new drug in the regimen.
Treatment options for some commonly seen
diseases
Insomnia
The prevalence of sleep disorders increases with age.
Older people tend to sleep earlier in the evening but also
wake up earlier. Some of them have fragmented sleep due
to repeated awakenings. This may be primary or secondary
to coexistent illness or medications. Pain due to arthritis
constitutes one of the most common causes of insomnia
in this population. Similarly nocturia due to diabetes or
prostatic disease is also a cause of sleep disturbances
and daytime fatigue. In these cases, treatment should
be targeted at the underlying disease to improve sleep
efficiency and unnecessary use of hypnotics should be
avoided. Moreover, simple measures like avoidance of
beverages in the night, voiding the bladder before going to
bed and shifting to a dark, quiet room may help the patient
in getting sleep.
However, if treatment for insomnia is needed, sedative –
hypnotics like benzodiazepines can be used. Care should be
taken to avoid long acting drugs like diazepam, flurazepam
and chlordiazepoxide as they cause drowsiness, confusion,
slurred speech, unsteady gait, falls and day time sleep. These
effects seem to be less with short acting benzodiazepines
like triazolam and oxazepam which may be effective for
sleep onset problems.16,26 In patients with early-morning
awakening, an intermediate agent such as temazepam
may be more useful. Similarly non-benzodiazepine drugs
like zolpidem, zaleplon, zopiclone and eszopiclone which
have little disruption on normal sleep architecture can also
be used.30
Arthritis
NSAIDs like aspirin are frequently prescribed in elderly
for diseases like rheumatoid arthritis, osteoarthritis, etc. GI
bleeding associated with such treatment is more common
in elderly patients. Selective COX-2 inhibitors seemed
to be promising candidates for long-term treatment
of chronic diseases, like arthritis due to their reduced
incidence of gastrointestinal adverse effects. However,
some of these agents have been withdrawn due to their
side effects like myocardial infarction and stroke. Hence,
non pharmacological measures like weight reduction,
warmth, exercise, use of a walking stick, etc. should be
tried first for diseases like osteoarthritis, rheumatoid
arthritis, soft tissue lesions and back pain. In case of pain,
analgesics like paracetamol or ibuprofen can be used.
If pain relief is inadequate with either drug an opioid
analgesic can be added.16 According to the Working Group
on Pain Management, an international multidisciplinary
panel, paracetamol is considered as baseline drug for the
© JAPI • VOL. 56 • JULY 2008
treatment of moderate-to-severe musculoskeletal pain
and for greater analgesia addition of a weak opioid is
recommended.31,32
Edema
Mild oedema can be treated by non-pharmacological
measures like elevation of legs, supportive stockings and
active life style. If treatment with diuretics is needed it has to
be restricted for fewer days. Diuretics prescribed irrationally
for a longer duration may lead to postural hypotension
and falls.16
Other drugs
Drug induced bleeding is commonly seen in elderly
and hence drugs like co-trimoxazole should be avoided
unless there is no other alternative. Similarly the dose of
anticoagulant like warfarin needs to be decreased as it
causes serious bleeding in them.16 Moreover neuroprotective
agents used in elderly people for stroke have not shown any
beneficial effects in the long run. Hence by avoiding these
drugs adherence can be improved.
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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529
objectives and guidelines may reduce unwanted adverse
reactions due to inappropriate or over prescribing in elderly
patients (Fig. 3). Some of the following points can be taken
into account to reduce ADRs.
a. Need for the treatment
Non pharmacological measures should be considered
as far as possible before starting treatment for diseases like
obesity, mild hypertension and atherosclerosis. They can be
controlled by altered life style, regular walking, reduced salt
intake, cessation of smoking and alcohol consumption.
b. Choosing the appropriate drug
If the patient needs treatment, most efficacious drug
with less ADR targeting the cause than symptom should
be selected. The associated illness like renal failure, hepatic
failure, cardiac failure, diabetes mellitus and hypertension
should be also be taken into consideration. Avoiding drugs
like â blockers in hypertensive patients with history of
asthma or reducing dose of digoxin in elderly with renal
failure can prevent unwanted ADR induced diseases.
c. Formulation
Prescribing drugs in the form of syrups, suspensions and
effervescent tablets can improve adherence in elderly as
they find it easy to swallow. Similarly care should be taken
not to give drugs in child-resistant containers as patients
with debilitating diseases may find it difficult to open.
d. Maintaining record and periodic review
Maintaining a drug record will help to check adherence,
possible drug interactions, ADR and the economic burden
of the patient. Patients receiving long term therapy should
be reviewed carefully to assess the need for the drug.
Depending on the disease condition the drug can be either
stopped or changed.
Difficulties in setting guidelines
Older generation represent a high proportion of the
population receiving drugs like NSAIDs for rheumatoid
arthritis and osteoarthritis.33 Moreover, 80% of deaths due to
acute myocardial infarction occur in people above 65 yrs of
age.34,35 Hence drugs used for these conditions will provide
information regarding ADRs only if used in this population.
However, for safety concern this special population is
usually not involved in clinical trials. This limits the ability
to generalize study findings in the elderly population
which experiences multiple diseases.36,37 Of these, diseases
like diabetes mellitus and hypertension are chronic and
are not always effectively treated with drugs. Moreover,
physiological changes and the resulting pharmacokinetic
variations differ among elderly individuals. These factors
make therapeutic decision making or setting guidelines for
an individual elderly patient more complex.
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.
REFERENCES
Fig. 3 : Principles of prescribing in elderly.4,16
530
1. Shah Naseem. Oral health care system for elderly in India. Geriatrics
and Gerontology International 2004;4:S162-64.
2. Joshi K , Kumar R, Avasthi A. Morbidity profile and its
relationship with disability and psychological distress among
elderly people in Northern India. Int J Epidemiol 2003;32:
978-87.
3. Taqui AM, Itrat A, Qidwai W, Qadri Z. Depression in the elderly: does
family system play a role? A cross-sectional study. BMC Psychiatry
2007;7:57.
4. Cusack BJ, Neilson CP, Vestal RE. Geriatric Clinical Pharmacology and
Therapeutics. In: Speight TM, Holford NHG, editors. Avery’s Drug
Treatment. Adis press Ltd., Auckland 1987;174-223.
5. Hanlon JT, Schmader KE, Kornkowski MJ, Weinberge M, Landsman PB,
Samsa GP, et al. Adverse drug events in high risk older outpatients. J
Am Geriatric Soc 1997;45:945-48.
6. Glass J, Lanctot KL, Herrmann N, Sproule BA, Busto UE. Sedative
hypnotics in older people with insomnia: meta-analysis of risks and
benefits. Br Med J 2005;331:1169.
7. Hemmelgarn B, Suissa S, Huang A, Boivin JF, Pinard G. Benzodiazepine
use and the risk of motor vehicle crash in the elderly. JAMA
1997;278:27-31.
8. Atkinson AJ. Effects of renal disease on pharmacokinetics. In:
www.japi.org
© JAPI • VOL. 56 • JULY 2008
Atkinson AJ, Daniels CE, Dedrick RL, Grudzinkas CV, Markey SP,
editors. Principles of Clinical Pharmacology. Academic Press, New
York 2001:43-9.
9. Wood AJ, Vestal RE, Wilkinson GR, Branch RA, Shand DG.
Effect of aging and cigarette smoking on antipyrine and
indocyanine green elimination. Clin Pharmacol Ther 1979; 26:
16-20.
10. Wynne HA, Cope LH, Mutch E, Rawlins MD, Woodhouse KW, James
OF. The effect of age upon liver volume and apparent liver blood flow
in healthy man. Hepatology 1989; 9:297-301.
11. Farah F, Taylor W, Rawlins MD, James O. Hepatic drug acetylation and
oxidation: effects of aging in man. Br Med J 1977; 2:155-6.
12. Bellantuono C, Reggi V, Tognoni G, Garattini S. Benzodiazepines:
clinical pharmacology and therapeutic use. Drugs 1980; 19:195219.
13. B e r t r a m G K a t z u n g . S p e c i a l a s p e c t s o f g e r i a t r i c
pharmacology. In: Bertram G Katzung, editor. Basic and
C l i n i c a l Ph a r m a co l o g y. M c G raw H i l l, N e w Yo r k 2 0 0 7 :
983-90.
14. Rowe JW, Andres R, Tobin JD, Norris AH, Shock NW. The effect of age
on creatinine clearance in men: a cross-sectional and longitudinal
study. J Gerontol 1976;31:155-63.
15. Cockcroft DW, Gault MH. Prediction of creatinine clearance from
serum creatinine. Nephron 1976; 16:31-41.
16. British National Formulary. BMJ and RPS Publishing, UK 2006:18-9.
17. Neilsen KS, Hansen JM, Kampmann J, Kristensen M. Rapid evaluation
of creativine clearance. Lancet 1971;1:1133-4.
18. Maeda Y, Omoda K, Fukuhara S, Ohta M, Ishii Y, Murkami
T. Evaluation of clinical efficacy of Maeda’s nomogram for
vancomycin dosage adjustment in adult Japanese MRSA
pneumonia patients. Drug Metab Pharmacokinet 2006;21:
54-60.
19. Bootman JL, Harrison DL, Cox E. The health care cost of drug –related
morbidity and mortality in nursing facilities. Arch Intern Med
1997;157:2089-96.
20. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug
reactions in hospitalized patients: a meta-analysis of prospective
studies. JAMA 1998;279:1200-05.
21. Nolan L, O’Malley K. Prescribing for the elderly. Part 1. Sensitivity
of the elderly to adverse drug reactions. J Am Geriatric Soc
1988;36:142-9.
22. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent
patterns of medication use in the ambulatory adult population of the
United States: the Slone survey. JAMA 2002;287:337-44.
23. Pham CB, Dickman RL. Minimising adverse drug events in older
patients. Am Fam Physician 2007;76:1837-44.
24. Grymonpre RE, Mitenko PA, Sitar DS, Aoki FY, Montgomery PR.
Drug - associated hospital admissions in older mental patients. J Am
Geriatric Soc 1988;36:1092-8.
25. Klein LE, German PS, Levine DM, Feroli ER, Ardery J. Medication
problems among outpatients. A study with emphasis on the elderly.
Arch Intern Med 1984;144:1185-8.
26. Beers MH, Ouslander JG, Rollinger J, Reuben DB, Beck JC.
Explicit criteria for determining inappropriate medication
use in nursing home residents. Arch Intern Med 1991;151:
1825-32.
27. Beers MH. Explicit criteria for determining potentially inappropriate
medication use by the elderly. Arch Intern Med 1997;157:1531-36.
28. Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH.
Updating the Beers criteria for potentially inappropriate medication
use in older adults: results of a US consensus panel of experts. Arch
Intern Med 2003;163:2716-24.
29. Avorn J, Gurwitz JH, Rochon P. Principles of Pharmacology.In: Cassel
CK, Leipzig RM, Cohen HJ, Larson EB, Meier DE, editors. Geriatric
Medicine, an evidence based approach. Springer, New York 2003:6581.
30. Wolkove N, Elkholy O, Baltzan M, Palayew M. Sleep and aging: 1. Sleep
© JAPI • VOL. 56 • JULY 2008
disorders commonly found in older people. CMAJ 2007;176:1299304.
31. S chnitzer TJ. Update on guidelines for the treatment
of chronic musculoskeletal pain. Clin Rheumatol 2006;25:
S22-9.
32. Straand J, Fetveit A, Rognstad S, Gjelstad S, Brekke M, Dalen I. A
cluster-randomized educational intervention to reduce inappropriate
prescription patterns for elderly patients in general practice—The
Prescription Peer Academic Detailing (Rx-PAD) study [NCT00281450].
BMC Health Serv Res 2006;6:72.
33. Hogan DB, Campbell NR, Crutcher R, Jennett, MacLeod N. Prescription
of nonsteroidal anti-inflammatory drugs for elderly people in Alberta.
CMAJ 1994;151:315–22.
34. Barone-Adesi F, Vizzini L, Merletti F, Richiardi L. Short-term effects of
Italian smoking regulation on rates of hospital admission for acute
myocardial infarction. Eur Heart J 2006;27:2468-72.
35. Singla I, Hreybe H, Saba S. Risk of death and recurrent ventricular
arrhythmias in survivors of cardiac arrest concurrent with acute
myocardial infarction. Indian Pacing Electrophysiol J 2008;8:5-13.
36. Lee PY, Alexander KP, Hammill BG, Pasquali SK, Peterson ED.
Representation of elderly persons and women in published
randomized trials of acute coronary syndromes. JAMA 2001;286:70813.
37. Rochon PA, Fortin PR, Dear KB, Minaker KL, Chalmers TC. Reporting of
age data in clinical trials of arthritis. Deficiencies and solutions. Arch
Intern Med 1993;153:243-8.
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