Abstract
Purpose
While some people remain fit and active as they grow older, others experience complex problems: disease, dependency and disability. Frailty is a term used to describe this latter group, capturing differences in health status among older people. Many frail older people have multiple chronic co-morbidities and functional impairments and, according to guidelines for the management of individual conditions, should be prescribed long lists of medications. However, older people (particularly those who are frail) are often excluded from drug trials, and treatment decisions are therefore based on evidence extrapolated from more robust patient groups with fewer physiological deficits. The risk of adverse drug reactions (ADRs) increases with increasing patient frailty, and polypharmacy has negative consequences above and beyond the risks of individual drugs. Increasing numbers of medications are associated with a higher likelihood of non-adherence and a significantly greater risk of ADRs. Older people taking five or more medications are at higher risk of delirium and falls, independent of medication indications.
Methods
This is a short review of the different approaches to defining and measuring frailty. We summarise the factors contributing to ADRs in frail older people and describe the pharmacokinetic and pharmacodynamics changes associated with ageing and frailty. By considering goals of care for frail older people, we explore how the appropriateness of medication prescribing for older people could be improved.
Conclusion
Since all physicians are likely to provide care for this group of vulnerable patients, understanding the concept of frailty may help to optimise medication prescribing for older people. The incorporation of frailty measures into future clinical studies of drug effects and pharmacokinetics is important if we are to improve medication use and guide drug doses for fit and frail older people.
Similar content being viewed by others
References
Louria DB (2005) Extraordinary longevity: individual and societal issues. J Am Geriatr Soc 53:S317–S319
Christensen K, Doblhammer G, Rau R, Vaupel JW (2009) Ageing populations: the challenges ahead. Lancet 374:1196–1208
Hajjar ER, Cafiero AC, Hanlon JT (2007) Polypharmacy in elderly patients. Am J Geriatr Pharmacother 5:345–351
Rockwood K, Mitnitski A, Song X, Steen B, Skoog I (2006) Long-term risks of death and institutionalization of elderly people in relation to deficit accumulation at age 70. J Am Geriatr Soc 54:975–979
Fried LP, Tangen CM, Walston J et al (2001) Frailty in older adults: evidence for a phenotype. J Gerontol Biol Med Sci 56:M146–M156
Rockwood K, Song X, Mitnitski A (2011) Changes in relative fitness and frailty across the adult lifespan: evidence from the Canadian National Population Health Survey. Can Med Assoc J 183:E487–E494
Chang SS, Weiss CO, Xue QL, Fried LP (2012) Association between inflammatory-related disease burden and frailty: results from the Women’s Health and Aging Studies (WHAS) I and II. Arch Gerontol Geriatr 54:9–15
Torres OH, Francia E, Longobardi V, Gich I, Benito S, Ruiz D (2006) Short- and long-term outcomes of older patients in intermediate care units. Intensive Care Med 32:1052–1059
Nardi R, Scanelli G, Corrao S, Iori I, Mathieu G, Cataldi Amatrian R (2007) Co-morbidity does not reflect complexity in internal medicine patients. Eur J Intern Med 18(5):359–368
Bandeen-Roche K, Xue QL, Ferrucci L et al (2006) Phenotype of frailty: characterization in the women’s health and aging studies. J Gerontol A Biol Sci Med Sci 61:262–266
Gill TM, Gahbauer EA, Han L, Allore HG (2010) Trajectories of disability in the last year of life. N Engl J Med 362:1173–1180
Hubbard RE, O’Mahony MS, Woodhouse KW (2009) Characterising frailty in the clinical setting—a comparison of different approaches. Age Ageing 38:115–119
Rolfson DB, Majumdar SR, Tahir AS, Tsuyuki RT (2001) Content validation of a frailty checklist derived from comprehensive geriatric assessment. Gerontology 47:119
Studenski S, Hayes RP, Leibowitz RQ et al (2004) Clinical Global Impression of Change in Physical Frailty: development of a measure based on clinical judgment. J Am Geriatr Soc 52:1560–1566
Rockwood K, Mitnitski A (2007) Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci 62:722–727
Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K (2008) A standard procedure for creating a frailty index. BMC Geriatr 8:24
Singh I, Davis K, Gallacher J, Johansen A, Eeles EMP, Hubbard RE (2012) Predictors of adverse outcome on an acute geriatric rehabilitation ward. Age Ageing 41:242–246
Hubbard RE, Eeles EM, Rockwood MR et al (2011) Assessing balance and mobility to track illness and recovery in older inpatients. J Gen Intern Med 26:1471–1478
Hubbard RE, O’Mahony MS, Savva GM, Calver BL, Woodhouse KW (2009) Inflammation and frailty measures in older people. J Cell Mol Med 13:3103–3109
Fried LP, Xue QL, Cappola AR et al (2009) Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci 64:1049–1057
UK Department of Health. Prescriptions dispensed in the community statistics for 1992–2002: England—prescription cost analysis 2002. Available at: http://www.publications.doh.gov.uk/Public/sb0312.htm
Van Spall HG, Toren A, Kiss A et al (2007) Eligibility criteria of randomised controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA 297:1233–1240
Pitt B, Zannad F, Remme WJ et al (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomised Aldactone Evaluation Study. N Eng J Med 341:709–717
Bozkurt B, Agoston I, Knowlton AA (2003) Complications of inappropriate use of spironolactone; when an old medicine spirals out of new guidelines. J Am Coll Cardiol 41:211–214
Svensson M, Gustafsson F, Galatius S, Hildebrandt PR, Atar D (2003) Hyperkalaemia and impaired renal function in patients taking spironolactone for congestive heart failure; retrospective study. Br Med J 327:1141–1142
Dinsdale C, Wani M, Steward J, O’Mahony MS (2005) Tolerability of spironolactone as adjunctive treatment for heart failure in patients over 75 years of age. Age Ageing 34:395–398
Martin FC, Brighton P (2008) Frailty: different tools for different purposes? Age Ageing 37(2):129–131
Willcox SM, Himmelstein DU, Woolhandler S (1994) Inappropriate drug prescribing for the community-dwelling elderly. JAMA 272:292–296
Gallagher PF, Barry PJ, Ryan C, Hartigan I, O’Mahony D (2008) Inappropriate prescribing in an acutely ill population of elderly patients as determined by Beers’ Criteria. Age Ageing 37:96–101
Somers E, Simmonds D, Whitelaw C, Calver J, Beer C (2010) Quality use of medicines in residential aged care. Aust Fam Phys 39:413–416
Gurwitz JH, Field TS, Avorn J et al (2000) Incidence and preventability of adverse drug events in nursing homes. Am J Med 109:87–94
The American Geriatrics Society 2012 Beers Criteria Update Expert Panel (2012) American Geriatrics Society updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 60:616–631
Laroche ML, Charmes JP, Nouaille Y, Picard N, Merle L (2007) Is inappropriate medication use a major cause of adverse drug reactions in the elderly? Br J Clin Pharmacol 63(2):177–186
Garner JB (2010) Problems of nonadherence in cardiology and proposals to improve outcomes. Am J Cardiol 105(10):1495–1501
Davies EC, Green CF, Taylor S et al (2009) Adverse drug reactions in hospital in-patients: a prospective analysis of 3695 patient-episodes. PLoS One 4:4439
Inouye SK (1998) Delirium in hospitalized older patients: recognition and risk factors. J Geriatr Psychiatry Neurol 11(3):118–125
Tinetti ME, Kumar C (2010) The patient who falls: “It’s always a trade-off”. JAMA 303(3):258–266
Masoro EJ (2010) Physiology of aging. In: Fillit HM, Rockwood K, Woodhouse K (eds) Brocklehurst’s textbook of geriatric medicine and gerontology, 7th edn. Elsevier, Philadelphia, pp 51–59
Klotz U (2009) Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev 41:67–76
Cusack BJ (2004) Pharmacokinetics in older persons. Am J Geriatr Pharmacother 2:274–302
Delafuente JC (2008) Pharmacokinetic and pharmacodynamic alterations in the geriatric patient. Consult Pharm 23:324–334
El Desoky ES (2007) Pharmacokinetic–pharmacodynamic crisis in the elderly. Am J Ther 14:488–498
Mangoni AA, Jackson SHD (2003) Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol 57:6–14
Currie GM, Wheat JM, Kiat H (2011) Pharmacokinetic considerations for digoxin in older people. Open Cardiovasc Med J 5:130–135
Gainsborough N, Maskrey VL, Nelson ML, Keating J, Sherwood RA, Jackson SH, Swift CG (1993) The association of age with gastric emptying. Age Ageing 22:37–40
Holt PR (2007) Intestinal malabsorption in the elderly. Dig Dis 25:144–150
Hubbard RE, Lang IA, Llewellyn DJ, Rockwood K (2010) Frailty, body mass index, and abdominal obesity in older people. J Gerontol A Biol Sci Med Sci 65(4):377–381
Weiss M (2008) How does obesity affect residence time dispersion and the shape of drug disposition curves? Thiopental as an example. J Pharmacokinet Pharmacodyn 35(3):325–336
Woodhouse KW, Wynne H, Baillie S, James O, Rawlins MD (1988) Who are the frail elderly? QJM 68:505–506
Wynne HA, Cope L, Herd B, James OFW, Rawlins MD, Woodhouse KW (1990) The association of age and frailty with paracetamol conjugation in man. Age Ageing 19:419–424
Wynne HA, Yelland C, Cope LH, Boddy A, Woodhouse KW, Bateman DN (1993) The association of age and frailty with the pharmacokinetics and pharmacodynamics of metoclopramide. Age Ageing 22:354–359
Williams FM (1987) Serum enzymes of drug metabolism. Pharmacol Ther 34(1):99–109
Kampmann JP, Hansen JM (1981) Clinical pharmacokinetics of antithyroid drugs. Clin Pharmacokinet 6(6):401–428
Kubo SH, Cody RJ (1985) Clinical pharmacokinetics of the angiotensin converting enzyme inhibitors. Clin Pharmacokinet 10(5):377–391
Yelland C, Summerbell J, Nicholson E, Herd B, Wynne H, Woodhouse KW (1991) The association of age with aspirin esterase activity in human liver. Age Ageing 20(1):16–18
Abou-Hatab K, O’Mahony MS, Patel S, Woodhouse K (2001) Relationship between age and plasma esterases. Age Ageing 30(1):41–45
O’Mahony MS, George G, Westlake H, Woodhouse K (1994) Plasma aspirin esterase activity in elderly patients undergoing elective hip replacement and with fractured neck of femur. Age Ageing 23:338–341
White S, Calver BL, Newsway V et al (2005) Enzymes of drug metabolism during delirium. Age Ageing 34(6):603–608
Abou-Hatab K, Ganeshalingam K, O’Mahony MS, Giurani F, Patel S, Woodhouse K (2001) The effect of community-acquired pneumonia on plasma esterases in older people. Eur J Clin Pharm 57:55–60
Abou-Hatab K, O’Mahony MS, Patel S, Carey D, Woodhouse K (2000) Plasma esterase activities in young and old patients undergoing open inguinal hernia repair. Arch Gerontol Geriatr 31:193–198
Summerbell J, Yelland C, Woodhouse KW (1990) The kinetics of plasma aspirin esterase in relation to old age and frailty. Age Ageing 19:128–130
Hubbard RE, O’Mahony MS, Calver BL, Woodhouse KW (2008) Plasma esterases and inflammation in ageing and frailty. Eur J Clin Pharmacol 64(9):895–900
Morgan ET (1997) Regulation of cytochrome p450 during inflammation and infection. Drug Metab Rev 29:1129–1188
Wynne HA, Cope LH, James OFW, Rawlins MD, Woodhouse KW (1989) The effect of age and frailty upon acetonilide clearance in man. Age Ageing 18:415–418
Rowe JW, Andres R, Tobin JD, Norris AM, Shock NW (1976) The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study. J Gerontol 31:155–163
Lindeman RD, Tobin J, Shock NW (1985) Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 33:278–285
Shlipak MG, Stehman-Breen C, Fried LF, Song X, Siscovick D, Fried LP et al (2004) The presence of frailty in elderly persons with chronic renal insufficiency. Am J Kidney Dis 43:861–867
Wilhelm-Leen ER, Hall YN, Tamura MK, Chertow GM (2009) Frailty and chronic kidney disease: the Third National Health and Nutrition Evaluation Survey. Am J Med 122(7):664–671, e2
Bao Y, Dalrymple L, Chertow GM, Kaysen GA, Johansen KL (2012) Frailty, dialysis initiation, and mortality in end-stage renal disease. Arch Intern Med 172:1071–1077
Johansen KL, Chertow GM, Jin C, Kutner NG (2007) Significance of frailty among dialysis patients. J Am Soc Nephrol 18:2960–2967
Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41
O’Riordan S, Ouldred E, Brice S, Jackson SH, Swift CG (2002) Serum cystatin C is not a better marker of creatinine or digoxin clearance than serum creatinine. Br J Clin Pharmacol 53:398–402
Levey AS, Bosch J, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461–470
Froissart M, Rossert J, Jaquot C, Paillard M, Houillier P (2005) Predictive performance of the Modification of Diet in Renal Disease and Cockcroft-Gault equations for estimating renal function. J Am Soc Nephrol 16:763–773
Trifiro G, Spina E (2011) Age-related changes in pharmacodynamics: focus on drugs acting on central nervous and cardiovascular systems. Curr Drug Metab 12(7):611–620
Routledge PA, Chapman PH, Davies DM, Rawlins MD (1979) Factors affecting warfarin requirements. A prospective population study. Eur J Clin Pharmacol 15(5):319–322
Pickering G, Jourdan D, Eschalier A, Dubray C (2002) Impact of age, gender and cognitive functioning on pain perception. Gerontology 48:112–118
McLachlan AJ, Bath S, Naganathan V et al (2011) Clinical pharmacology of analgesic medicines in older people: impact of frailty and cognitive impairment. Br J Clin Pharmacol 71(3):351–364
Holmes HM, Hayley DC, Alexander GC, Sachs GA (2006) Reconsidering medication appropriateness for patients late in life. Arch Intern Med 166:605–609
Scott IA, Gray LC, Martin JH, Mitchell CA (2012) Minimizing inappropriate medications in older populations: a 10-step conceptual framework. Am J Med 125(6):529–537
Mallery LH, Moorhouse P (2011) Respecting frailty. J Med Ethics 37(2):126–128
Scott IA, Guyatt GH (2010) Cautionary tales in the interpretation of clinical studies involving older persons. Arch Intern Med 170(7):587–595
Rockwood K, Hubbard R (2004) Frailty and the geriatrician. Age Ageing 33(5):429–430
Rockwood K, Joyce B, Stolee P (1997) Use of goal attainment scaling in measuring clinically important change in cognitive rehabilitation patients. J Clin Epidemiol 50(5):581–588
Fried TR, Tinetti ME, Towle V, O’Leary JR, Iannone L (2011) Effects of benefits and harms on older persons’ willingness to take medication for primary cardiovascular prevention. Arch Intern Med 171:923–928
Eeles EMP, White SV, O’Mahony MS, Bayer AJ, Hubbard RE (2012) The impact of frailty and delirium on mortality in older inpatients. Age Ageing 41(3):412–416
Berthold HK, Gouni-Berthold I (2011) Lipid-lowering drug therapy in elderly patients. Curr Pharm Des 17:877–893
Hines LE, Murphy JE (2011) Potentially harmful drug-drug interactions in the elderly: a review. Am J Geriatr Pharmacother 9(6):364–377
Hollick RJ, Reid DM (2011) Role of bisphosphonates in the management of postmenopausal osteoporosis: an update on recent safety anxieties. Menopause Int 17(2):66–72
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hubbard, R.E., O’Mahony, M.S. & Woodhouse, K.W. Medication prescribing in frail older people. Eur J Clin Pharmacol 69, 319–326 (2013). https://doi.org/10.1007/s00228-012-1387-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-012-1387-2