British Journal of Medical Practitioners, Sept.

2008, Volume 1, Number 1

Review

BJMP 2008:1(1) 6-9

POLYPHARMACY: TO ERR IS HUMAN, TO CORRECT DIVINE

Nasseer A. Masoodi

ABSTRACT
Objectives
Optimizing drug therapy for elderly is often challenging. Sometimes treatment causes more harm than the disease. The aim of this article
is to review the body of literature addressing polypharmacy to determine its definition, explore how polypharmacy was assessed in primary
care, and seek evidence based interventions that address polypharmacy.
Data Sources
An electronic search of the PUBMED database utilizing the search terms polypharmacy, polypharmacy and elderly, adverse drug
reactions, multiple medications, inappropriate prescribing, and Beers criteria was performed and the search was supplemented with
online site searches of relevant journals and review of reference lists of each article.
Results and discussion
Prescription of potentially inappropriate medications to older people is highly prevalent in the United States and Europe. Polypharmacy
continues to be a significant issue. There is a gap in the literature regarding the interventions implemented by physicians to address
polypharmacy. There are no robust prospective studies that test the clinical benefit to patients of using drug utilization review tools.
Conclusion
There is no specific definition for polypharmacy. It has been defined in many different ways depending upon patient population and
study settings. Prospective randomized controlled trials are needed to identify useful interventions. Drug utilization review tools should be
designed on the basis of a countrys national drug formulary and should be evidence based as most existing drug utilization review tools
have been designed on the basis of North American system.

INTRODUCTION:
INTRODUCTION:
Population demographics are changing worldwide, with life
expectancy and the proportions of older persons increasing.
Older people are the greatest consumers of medications and
healthcare resources in developed countries. It is assumed that
as more drugs become available and life expectancy continues to
increase, the consumption of prescription drugs by older people
will increase further and the incidence of potentially
inappropriate prescribing will grow. A survey of noninstitutionalized older adults in the United States showed an
increased usage of all medications with advancing age, the
highest prevalence of drug use being in women 65 years of age
and older with 12% taking 10 or more medications and 23%
taking at least five prescribed drug therapies 1. In most
industrialized nations older people consume three times as
many prescription medications as younger people and purchase
70% of non-prescription medications 2. In the United States,
125% of the population is over 65 years of age but consume
32% of all prescription medications and account for 25% of
drug expenditure and 30% of total national healthcare
expenditure 3-5. In Ireland, 1113% of population is over the
age of 65 years but consume 47% of all prescription
medications 6. In Europe, people over 65 years of age consume

on average 23 times the amount of health care than do those

<65 years of age 7.
POLYPHARMACY:
Polypharmacy has been defined in many different ways and the
appropriate definition may differ according to patient
population and study setting 9. Fulton and Allen 10 define
polypharmacy as: 'the use of medications that are not clinically
indicated'. In practice, polypharmacy is defined as using more
than a certain number of drugs, irrespective of the
appropriateness of drug use 8, 11, 12. Inappropriate prescribing
includes the use of medicines that introduce a significant risk of
an adverse drug-related event where there is evidence for an
equally or more effective but lower-risk alternative therapy
available for treating the same condition. Inappropriate
prescribing also includes the use of medicines at a higher
frequency and for longer than clinically indicated, use of
multiple medicines that have recognized drugdrug interactions
and drugdisease interactions, and importantly, the under-use
of beneficial medicines that are clinically indicated but not
prescribed for some reasons. As older patients seek treatment for
various ailments from a variety of physicians, they are at
increasing risk of accumulating layers of drug therapy.
Individuals aged 65 and older use a disproportionate number of
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British Journal of Medical Practitioners, Sept. 2008, Volume 1, Number 1

prescriptions and over-the-counter medications; 31% use more

than one pharmacy and 50% receive prescriptions from more
than one prescriber 13. A higher number of primary care
physicians and multiple dispensing pharmacies increase the risk
of drugdrug interactions 14. The number of medications
prescribed to elderly patients, and the complexity of their drug
regimens increase over time 15.
The potential for an increased risk of drugdrug interactions
and adverse drug reactions, and factors such as age-related
changes in pharmacodynamics (PD) and pharmacokinetics
(PK) must be considered. Diabetes and chronic lung disease
predict a greater complexity and cost of drugs regimen in
elderly patients with heart failure 16. Besides the increase in
diseases and worsening of diseases, the literature also mentions
other factors as being responsible for the increase in
polypharmacy, i.e. ageing, moving to a residential or nursing
home and hospitalization 17, 18. The patient's expectations, the
General Practitioner's attitude and consultations with several
doctors have been associated with an increase in multiple drug
use 19, 20.

EFFECTS OF AGING ON DRUG METABOLISM:

METABOLISM
Drug absorption, distribution, metabolism and elimination
change as a natural consequence of the ageing process. Changes
in drug absorption in older patients may result from decreases
in splanchnic blood flow and gastric motility, and increases in
gastric pH, and other physiological changes that are associated
with ageing. Blood flow and gastric motility may be further
diminished by cardiovascular and gastrointestinal drugs used to
treat co-morbid conditions. Ageing influences drug excretion.
Age-related decreases in glomerular filtration rate are well
known. These physiological declines coupled with co-morbid
conditions and the use of multiple drugs means that
medications eliminated by the renal route requires dose
adjustment. Drugs that influence renal function and thus
elimination/excretion have the potential to pose serious clinical
problems if used concomitantly. With ageing, there is a
decrease in lean body mass and total body water with a relative
increase in total body fat 21. These changes lead to a decreased
volume of distribution for hydrophilic drugs such as lithium,
and digoxin where unadjusted dosing can result in higher
plasma concentrations, thus increasing the potential for adverse
effects. Conversely, lipid soluble drugs such as long-acting
benzodiazepines have an increased volume of distribution,
thereby delaying their maximal effects and resulting in
accumulation with continued use. There is a reduction in
hepatic mass and blood flow with ageing 22.
Drugs such as beta-blockers, nitrates and tricyclic antidepressants that have a first pass effect in the liver may have a
higher bioavailability in older people and thus be effective at
lower doses. Cytochrome P450 oxidation declines with ageing
24
and drugdrug interactions involving these enzymes are
important to recognize. Larger drug storage reservoirs and
decreased clearance prolong drug half-lives and lead to increased
plasma drug concentrations in older people. If serum albumin is
decreased there will be an increase in the active unbound drug
concentration for highly protein-bound drugs such as
phenytoin, theophylline, warfarin and digoxin. Ageing is also

associated with changes in the end-organ responsiveness to

drugs at receptor or post-receptor level 25. There is decreased
sensitivity to beta-receptors along with a possible decreased
clinical response to beta-blockers and beta-agonists 26. Increased
sensitivity to drugs such as opiates and warfarin is common 27,
28
.
ADVERSE DRUG REACTIONS (ADRs):
The number of elderly is increasing dramatically. In United
States, in the next 25 years, as the baby boomer generation
begins to turn 65 years old, the number of elderly is expected to
double to approximately 70 million. Those older than 85, is
now the fastest growing segment of our population. Thus, we
can expect the number of adverse drug reactions to increase
proportionately. Polypathology, the age-related increase of
concurrent diseases, is likely to be the main determinant of drug
consumption. However, both over-prescribing and improper
prescribing has been reported and seems to contribute to the
age-related increase in the prevalence of adverse drug reactions
(ADRs) 29, 30. A hospital-based study from Norway showed that
the risk of experiencing a drug-related problem increased
linearly with the number of drugs on admission 31. A study
carried out in the USA found that nursing home patients
receiving nine or more drugs were more than twice as likely as
patients receiving a lower number of drugs, of experiencing an
adverse effect 32. On average, ADRs account for 3%13% of all
the admissions 33-35 and complicate 5%20% of the stays of
patients over 65 years 36-38. More than 40% of persons aged 65
and older use five or more different medications per week, and
12% use 10 or more different medications 39. If an elderly
patient takes five or more drugs, he or she has a 35% chance of
experiencing an adverse drug event 40.
Drug interactions are significant contributors to morbidity 35.
Office visits for an adverse drug event increase from 9% of the
population per year at age 2544 years to as high as 568%
between age 65 and 74 years 41. Inappropriate drug use is one of
the risk factors for adverse drug reactions in the elderly. The
risk for an adverse drug event is 13% with the use of two
medications, but the risk increases to 58% for five medications
42
. If seven or more medications are used, the incidence of
adverse drug events increases to 82% 42.
INTERVENTIONS:
Older people are a heterogenous group, often with multiple
concomitant illnesses and multiple prescriptions. There is a thin
line between a healthy old person and an ill old person.
Prescribing for older people is challenging as any new
medication must be considered in the context of altered
pharmacokinetics, altered pharmacodynamics and age-related
changes in body composition and physiology. Both over
prescription and undue prescription seem to characterize the
overall pharmacological therapy of the elderly.
Polypharmacy is the main risk factors for ADRs 43. Thus,
attempts should be made to curtail inappropriate drug
prescription by utilizing different available tools 44. An
interdisciplinary medication review of older individuals in the
community helps to reduce the cost and number of
medications. Polypathology seems the most obvious
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British Journal of Medical Practitioners, Sept. 2008, Volume 1, Number 1

explanation of the high number of drugs taken by older people,

but additional factors deserve consideration. Changes in
patients medical status over time can cause medications that
have been used chronically to become unsafe or ineffective.
Particular care must be taken in determining drug dosages and
treatment options when prescribing for older adults. Pill for an
ill approach should be discouraged as many a time
pharmacological treatment may carry more adverse effects then
the illness itself. Use of electronic medical records and other
hand held devices to prescribe appropriate medication doses
and check drug to drug interactions has been found useful in
reducing the medication related errors and hence adopted by
various medical groups and hospital practices.

REFERENCES
1.

2.

3.

4.

5.

Reviewing medications at every visit is a simple and very

helpful tool too especially if patients are encouraged to bring
with them a printed list of their current medications (including
over the counter drugs). Printing an updated list of the
medication changes in bold and large font after a visit with their
physician helps patients to follow the recommendations
especially in case of geriatric patients who may not remember
all the new changes made at an office visit.
CONCLUSIONS:
Polypharmacy is an important issue in the elderly. The problem
involves many issues, a number of which have been explored in
this article. One of the most important issues involves adverse
drug reactions. All pharmaceutical agents have the potential for
side effects; therefore, it is obvious that the more drugs one
takes the more side effects one will experience. The aging
process results in altered metabolism and excretion of
medications, and deficits in cognition and senses. Incidence of
adverse drug reaction and interactions is increased with
polypharmacy. Since adverse drug reactions are a significant
cause of morbidity and mortality, as well as an important cause
for hospital admissions, minimizing polypharmacy is an
important consideration. The general principle of Start Low
and Go Slow holds true in most scenarios but should be
modified to Start Low, Go Slow but Use Enough to achieve
desired therapeutic effect.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

COMPETEING INTERESTS:
INTERESTS:
Serves as a speaker for Eisai Inc. and Pfizer Inc. for the 2008 ARICEPT
LTC DELTA 2 (Dementia Education Leadership Training in
Alzheimer's) Promotional Education Program
AUTHOR DETAILS
NASSEER A. MASOODI, MD, FACP, CMD. Assistant Professor
Clinical Sciences, Florida State University College of Medicine,
Tallahassee, FL-USA; Courtesy Assistant Professor Geriatrics,
University of Florida College of Medicine, Gainesville, FL-USA;
Medical Director Health Services, ACV Inc, Dowling Park, FL-USA

16.

17.

18.

19.

CORRESSPONDENCE: PO BOX: 4346, Dowling Park, FL-32064,

USA.
Email: [email protected]

20.

21.

22.

Kaufman DW, Kelly JP, Rosenberg L et al. (2002) Recent patterns

of medication use in the ambulatory adult population of the
United States: The Slone Survey. JAMA, 287, 337.
Christchilles EA, Foley DJ, Wallace RB et al. (1992) Use of
medications by persons 65 and over: data from the established
populations for epidemiologic studies of the elderly. Journal of
Gerontology, 47, 137144.
Arnett RH III, Blank LA, Brown AP et al. (1990) National Health
Expenditures 1988. Office of National Cost Estimates. Health
Care Financing Review, 11, 141.
Gupta S, Rappaport HM, Bennett LT (1996) Inappropriate drug
prescribing and related outcomes for elderly Medicaid beneficiaries
residing in nursing homes. Clinical Therapeutics, 18, 183196.
Golden AG, Preston RA, Barnett SD et al. (1999) Inappropriate
prescribing in homebound older adults. Journal of the American
Geriatrics Society, 47, 948953.
Barry M (2002) Drug Expenditure in Ireland 19912001. IMJ,
95, 45.
O'Connor K, O'Mahony D (2003) Drugs and ageing. In: Liston
R, Mulkerrin EC, eds. Medicine for older patients: cases and
practice. Dublin, Ireland: Eireann Healthcare Publications, 205.)
Nguyen JK, Fouts MM, Kotabe SE, Lo E (2006) Polypharmacy as
a risk factor for adverse drug reactions in geriatric nursing home
residents. The American Journal of Geriatric Pharmacotherapy, 4,
3641.
9. Rollason V, Vogt N (2003) Reduction of polypharmacy in the
elderly: a systematic review of the role of the pharmacist. Drugs
and Aging, 20, 817832.
Fulton MM, Allen ER (2005) Polypharmacy in the elderly: a
literature review. Journal of the American Academy of Nurse
Practitioners, 17, 123132.
Koh Y, Fatimah BM, Li SC (2003) Therapy related hospital
admission in patients on polypharmacy in Singapore: a pilot study.
Pharmacy World and Science, 25, 135137.
Mamun K, Lien CT, Goh-Tan CY, Ang WS (2004) Polypharmacy
and inappropriate medication use in Singapore nursing homes.
Annals of the Academy of Medicine, Singapore, 33, 4952.
Safran D, Neuman P, Schoen C et al. (2005) Prescription drug
coverage and seniors: findings from a 2003 national survey. Health
Affairs (Millwood), JanJun, Supplemental Web Exclusive: W5152W5-166.
Becker ML, Kallewaard M, Caspers PW, Schalekamp P, Stricker
BH (2005) Potential determinants of drugdrug interactions
associated with dispensing in community pharmacies. Drug Safety:
An International Journal of Medical Toxicology and Drug
Experience, 28, 371378.
Cherry DK, Woodwell DA (2002) National Ambulatory Medical
Care Survey: 2000 summary. Advance Data, 328, 132.)
Masoudi FA, Baillie CA, Wang Y, et al. The complexity and cost
of drug regimens of older patients hospitalized with heart failure in
the United States, 19982001. Arch Intern Med. 2005; 165:2069
76.
Hale WE, May FE, Marks RG, Stewart RB. Drug use in an
ambulatory elderly population: a five-year update. Drug Intell Clin
Pharm 1987; 21: 530535.
Simons LA, Tett S, Simons J et al. Multiple medication use in the
elderly. Use of prescription and non-prescription drugs in an
Australian community setting. Med J Aust 1992; 157: 242246
Sharpe TR, Smith MC, Barbre AR. Medicine use among the rural
elderly. J Health Soc Behav 1985; 26: 113127.
Williams P, Rush DR. Geriatric polypharmacy. Hosp Pract 1986;
21: 109120
Meyer BR (2003) Clinical pharmacology and ageing. In: Grimley
Evans J, Franklin Williams T, Lynn Beattie B, Michael J-P,
Wilcock G, eds. Oxford textbook of geriatric medicine, 2nd edn.
Oxford: Oxford University Press, 127136.
Woodhouse KW, Ewynne HA (1988) Age related changes in liver
size and hepatic blood flow: the influence of drug metabolism in
the elderly. Clinical Pharmacokinetics, 15, 328344.
8

BJMP.org

British Journal of Medical Practitioners, Sept. 2008, Volume 1, Number 1

23.

24.

25.

26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

Hunt CM, Westerkam WR, Stave GM et al. (1992) Hepatic

cytochrome P-4503A (CYP3A) activity in the elderly. Mechanisms
of Ageing and Development, 64, 189.
Hunt CM, Westerkam WR, Stave GM (1992) Effect of age and
gender on the activity of human hepatic CYP3A. Biochemical
Pharmacology, 44, 275.
Vestal RE, Wood AJJ, Shand DG (1988) Adrenoreceptor status
and cardiovascular function in ageing. Journal of Hypertension,
6(Suppl. 1), S59S62
Vestal RE, Wood AJJ, Shand DG (1979) Reduced beta
adrenoceptor sensitivity in the elderly. Clinical Pharmacology and
therapeutics, 26, 181186.
Gage BF, Fihn SD, White RH (2000) Management and dosing of
warfarin therapy. American Journal of Medicine, 109, 481.
Beers MH, Berkow R eds (2000) Clinical Pharmacology. The
Merck manual of geriatrics, 3rd edn. White house Station, NJ:
Merck Research Laboratories, 5474.)
Onder G, Pedone C, Landi F, et al. Adverse drug reactions as cause
of hospital admissions: results from the Italian Group of
Pharmacoepidemiology in the Elderly (GIFA). J Am Geriatr Soc.
2002; 50:19628.
Chang CM, Liu PY, Yang YH, et al. Use of the Beers criteria to
predict adverse drug reactions among first-visit elderly outpatients.
Pharmacotherapy. 2005;25:8318.
Viktil KK , Blix HS, Moger TA, Reikvam A (2007) Polypharmacy
as commonly defined is an indicator of limited value in the
assessment of drug-related problems. British Journal of Clinical
Pharmacology, 63, 187195
Nguyen JK, Fouts MM, Kotabe SE, Lo E (2006) Polypharmacy as
a risk factor for adverse drug reactions in geriatric nursing home
residents. The American Journal of Geriatric Pharmacotherapy, 4,
3641
Atkin PA, Shenfield GM. Medication-related adverse reactions and
the elderly: a literature review. Adv Drug React Toxicol Rev. 1995;
14:17591.
Mannesse CK, Derkx FH, de Ridder MA, et al. Contribution of
adverse drug reactions to hospital admission of older patients. Age
Ageing. 2000; 29:359.
Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions
as cause of admission to hospital: prospective analysis of 18 820
patients. BMJ. 2004; 329:1519.

36.

37.

38.

39.

40.

41.

42.

43.

44.

Onder G, Gambassi G, Scales CJ, et al. 2002. Adverse drug

reactions and cognitive function among hospitalized older adults.
Eur J Clin Pharmacol, 58:3717.
Somers A, Petrovic M, Robays H, et al. 2003. Reporting adverse
drug reactions on a geriatric ward: a pilot project. Eur J Clin
Pharmacol, 58:70714.
Corsonello A, Pedone C, Corica F, et al. 2005. Concealed renal
insufficiency and adverse drug reactions in elderly hospitalized
patients. Arch Intern Med, 165:7905.
Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA
(2002) Recent patterns of medication use in the ambulatory adult
population of the United States: the Slone survey. The Journal of
the American Medical Association, 287, 337344.
Lazarou J, Pomeranz BH, Corey PN (1998) Incidence of adverse
drug reactions in hospitalized patients: a meta-analysis of
prospective studies. The Journal of the American Medical
Association, 279, 12001205.
Zhan C, Arispe I, Kelley E, Ding T, Burt CW, Shinogle J, Stryer
D (2005) Ambulatory care visits for treating adverse drug effects in
the United Sates, 19952001. Joint Commission Journal on
Quality of Patient Safety, 31, 372378
Prybys, K., Melville, K., Hanna, J., Gee, A., & Chyka, P. (2002).
Polypharmacy in the elderly: Clinical challenges in emergency
practice: Part 1: Overview, etiology, and drug interactions.
Emergency Medicine Reports, 23(11), 145153.
Hajjar ER, Hanlon JT, Artz MB, et al. Adverse drug reaction risk
factors in older outpatients. Am J Geriatr Pharmacother. 2003;
1:829.
Beers, M. (1997). Explicit criteria for determining potentially
inappropriate medication use by the elderly: An update. Archives of
Internal
Medicine,157(14),15311537.

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