Skip to main content
Top
Published in: Drugs & Aging 5/2013

01-05-2013 | Original Research Article

Anticholinergic Drug Use, Serum Anticholinergic Activity, and Adverse Drug Events Among Older People: A Population-Based Study

Authors: Pasi Lampela, Piia Lavikainen, J. Arturo Garcia-Horsman, J. Simon Bell, Risto Huupponen, Sirpa Hartikainen

Published in: Drugs & Aging | Issue 5/2013

Login to get access

Abstract

Background

The serum anticholinergic activity (SAA) assay has been used to quantify patients’ anticholinergic load. In addition, several ranked lists of anticholinergic drugs have been developed to assess anticholinergic drug burden.

Objective

This study investigated whether SAA assay results and scores from three ranked lists of anticholinergic drugs (Carnahan’s Anticholinergic Drug Scale, Rudolph’s Anticholinergic Risk Scale, and Chew’s list) are associated with anticholinergic adverse drug events (ADEs) in older people.

Methods

We analyzed data from participants in the population-based Geriatric Multidisciplinary Good Care of the Elderly Study in Kuopio, Finland (n = 621). Demographic, diagnostic, and drug use data were collected during standardized interviews and verified from medical records. Vision, functional capacity, cognition, and mood were assessed using validated techniques. The SAA was measured from blood samples.

Results

The SAA was not associated with anticholinergic ADEs. Anticholinergic drug burden computed using each of the three lists was inversely associated with short-distance vision (p < 0.01), activities of daily living (p < 0.05), and instrumental activities of daily living (p < 0.05) in persons with and without dementia. Furthermore, poorer Mini Mental State Examination and poorer Geriatric Depression Scale scores were associated with the anticholinergic drug burden in persons without dementia (p < 0.05–p < 0.001). The association between anticholinergic drug burden and ADEs was strongest when using the lists developed by Carnahan and Chew.

Conclusions

Scores obtained from ranked lists of anticholinergic drugs were associated with clinically significant anticholinergic ADEs but the SAA was not. This finding supports the usefulness of these lists to help identify patients at risk of anticholinergic ADEs in clinical practice.
Literature
1.
go back to reference Nishtala PS, Fois RA, McLachlan AJ, et al. Anticholinergic activity of commonly prescribed medications and neuropsychiatric adverse events in older people. J Clin Pharmacol. 2009;49:1176–84.PubMedCrossRef Nishtala PS, Fois RA, McLachlan AJ, et al. Anticholinergic activity of commonly prescribed medications and neuropsychiatric adverse events in older people. J Clin Pharmacol. 2009;49:1176–84.PubMedCrossRef
2.
go back to reference Chew ML, Mulsant BH, Pollock BG, et al. Anticholinergic activity of 107 medications commonly used by older adults. J Am Geriatr Soc. 2008;56:1333–41.PubMedCrossRef Chew ML, Mulsant BH, Pollock BG, et al. Anticholinergic activity of 107 medications commonly used by older adults. J Am Geriatr Soc. 2008;56:1333–41.PubMedCrossRef
3.
go back to reference Carrière I, Fourrier-Reglat A, Dartigues JF, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Arch Intern Med. 2009;169:1317–24.PubMedCrossRef Carrière I, Fourrier-Reglat A, Dartigues JF, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Arch Intern Med. 2009;169:1317–24.PubMedCrossRef
4.
go back to reference Uusvaara J, Pitkälä KH, Kautiainen H, et al. Association of anticholinergic drugs with hospitalization and mortality among older cardiovascular patients: a prospective study. Drugs Aging. 2011;28:131–8.PubMedCrossRef Uusvaara J, Pitkälä KH, Kautiainen H, et al. Association of anticholinergic drugs with hospitalization and mortality among older cardiovascular patients: a prospective study. Drugs Aging. 2011;28:131–8.PubMedCrossRef
5.
go back to reference Flynn RA, Glynn DA, Kennedy MP. Anticholinergic treatment in airways diseases. Adv Ther. 2009;26:908–19.PubMedCrossRef Flynn RA, Glynn DA, Kennedy MP. Anticholinergic treatment in airways diseases. Adv Ther. 2009;26:908–19.PubMedCrossRef
6.
go back to reference Wawruch M, Macugova A, Kostkova L, et al. The use of medications with anticholinergic properties and risk factors for their use in hospitalised elderly patients. Pharmacoepidemiol Drug Saf. 2012;21:170–6.PubMedCrossRef Wawruch M, Macugova A, Kostkova L, et al. The use of medications with anticholinergic properties and risk factors for their use in hospitalised elderly patients. Pharmacoepidemiol Drug Saf. 2012;21:170–6.PubMedCrossRef
7.
go back to reference Dewey SL, Volkow ND, Logan J, et al. Age-related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET). J Neurosci Res. 1990;27:569–75.PubMedCrossRef Dewey SL, Volkow ND, Logan J, et al. Age-related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET). J Neurosci Res. 1990;27:569–75.PubMedCrossRef
8.
go back to reference Kay GG, Ebinger U. Preserving cognitive function for patients with overactive bladder: evidence for a differential effect with darifenacin. Int J Clin Pract. 2008;62:1792–800.PubMedCrossRef Kay GG, Ebinger U. Preserving cognitive function for patients with overactive bladder: evidence for a differential effect with darifenacin. Int J Clin Pract. 2008;62:1792–800.PubMedCrossRef
9.
go back to reference Farrall AJ, Wardlaw JM. Blood-brain barrier: ageing and microvascular disease–systematic review and meta-analysis. Neurobiol Aging. 2009;30:337–52.PubMedCrossRef Farrall AJ, Wardlaw JM. Blood-brain barrier: ageing and microvascular disease–systematic review and meta-analysis. Neurobiol Aging. 2009;30:337–52.PubMedCrossRef
10.
go back to reference Stolp HB, Dziegielewska KM. Review: role of developmental inflammation and blood-brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases. Neuropathol Appl Neurobiol. 2009;35:132–46.PubMedCrossRef Stolp HB, Dziegielewska KM. Review: role of developmental inflammation and blood-brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases. Neuropathol Appl Neurobiol. 2009;35:132–46.PubMedCrossRef
11.
go back to reference Weiss N, Miller F, Cazaubon S, et al. The blood-brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta. 2009;1788:842–57.PubMedCrossRef Weiss N, Miller F, Cazaubon S, et al. The blood-brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta. 2009;1788:842–57.PubMedCrossRef
12.
go back to reference Tune L, Coyle JT. Serum levels of anticholinergic drugs in treatment of acute extrapyramidal side effects. Arch Gen Psychiatry. 1980;37:293–7.PubMedCrossRef Tune L, Coyle JT. Serum levels of anticholinergic drugs in treatment of acute extrapyramidal side effects. Arch Gen Psychiatry. 1980;37:293–7.PubMedCrossRef
13.
go back to reference Tune L, Carr S, Hoag E, et al. Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium. Am J Psychiatry. 1992;149:1393–4.PubMed Tune L, Carr S, Hoag E, et al. Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium. Am J Psychiatry. 1992;149:1393–4.PubMed
14.
go back to reference Han L, Agostini JV, Allore HG. Cumulative anticholinergic exposure is associated with poor memory and executive function in older men. J Am Geriatr Soc. 2008;56:2203–10.PubMedCrossRef Han L, Agostini JV, Allore HG. Cumulative anticholinergic exposure is associated with poor memory and executive function in older men. J Am Geriatr Soc. 2008;56:2203–10.PubMedCrossRef
15.
go back to reference Carnahan RM, Lund BC, Perry PJ, et al. The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity. J Clin Pharmacol. 2006;46:1481–6.PubMedCrossRef Carnahan RM, Lund BC, Perry PJ, et al. The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity. J Clin Pharmacol. 2006;46:1481–6.PubMedCrossRef
16.
go back to reference Minzenberg MJ, Poole JH, Benton C, et al. Association of anticholinergic load with impairment of complex attention and memory in schizophrenia. Am J Psychiatry. 2004;161:116–24.PubMedCrossRef Minzenberg MJ, Poole JH, Benton C, et al. Association of anticholinergic load with impairment of complex attention and memory in schizophrenia. Am J Psychiatry. 2004;161:116–24.PubMedCrossRef
17.
go back to reference Rudolph JL, Salow MJ, Angelini MC, et al. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. 2008;168:508–13.PubMedCrossRef Rudolph JL, Salow MJ, Angelini MC, et al. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. 2008;168:508–13.PubMedCrossRef
18.
go back to reference Ancelin ML, Artero S, Portet F, et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006;332:455–9.PubMedCrossRef Ancelin ML, Artero S, Portet F, et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006;332:455–9.PubMedCrossRef
19.
go back to reference Penttilä J, Scheinin H, Syvälahti E. Measurement of anticholinergic effects of psychotropic drugs in humans. Pharmacopsychiatry. 2005;38:187–93.PubMedCrossRef Penttilä J, Scheinin H, Syvälahti E. Measurement of anticholinergic effects of psychotropic drugs in humans. Pharmacopsychiatry. 2005;38:187–93.PubMedCrossRef
20.
go back to reference Lampela P, Hartikainen S, Sulkava R, et al. Adverse drug effects in elderly people – a disparity between clinical examination and adverse effects self-reported by the patient. Eur J Clin Pharmacol. 2007;63:509–15.PubMedCrossRef Lampela P, Hartikainen S, Sulkava R, et al. Adverse drug effects in elderly people – a disparity between clinical examination and adverse effects self-reported by the patient. Eur J Clin Pharmacol. 2007;63:509–15.PubMedCrossRef
21.
go back to reference Lampela P, Hartikainen S, Lavikainen P, et al. Effects of medication assessment as part of a comprehensive geriatric assessment on drug use over a 1-year period: a population-based intervention study. Drugs Aging. 2010;27:507–21.PubMedCrossRef Lampela P, Hartikainen S, Lavikainen P, et al. Effects of medication assessment as part of a comprehensive geriatric assessment on drug use over a 1-year period: a population-based intervention study. Drugs Aging. 2010;27:507–21.PubMedCrossRef
22.
go back to reference Rikala M, Hartikainen S, Sulkava R, et al. Validity of the Finnish Prescription Register for measuring psychotropic drug exposures among elderly Finns: a population-based intervention study. Drugs Aging. 2010;27:337–49.PubMedCrossRef Rikala M, Hartikainen S, Sulkava R, et al. Validity of the Finnish Prescription Register for measuring psychotropic drug exposures among elderly Finns: a population-based intervention study. Drugs Aging. 2010;27:337–49.PubMedCrossRef
23.
go back to reference van der Putten JJ, Hobart JC, Freeman JA, et al. Measuring change in disability after inpatient rehabilitation: comparison of the responsiveness of the Barthel index and the Functional Independence Measure. J Neurol Neurosurg Psychiatry. 1999;66:480–4.PubMedCrossRef van der Putten JJ, Hobart JC, Freeman JA, et al. Measuring change in disability after inpatient rehabilitation: comparison of the responsiveness of the Barthel index and the Functional Independence Measure. J Neurol Neurosurg Psychiatry. 1999;66:480–4.PubMedCrossRef
24.
go back to reference Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9:179–86.PubMedCrossRef Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9:179–86.PubMedCrossRef
25.
go back to reference Crum RM, Anthony JC, Bassett SS, et al. Population-based norms for the Mini-Mental State Examination by age and educational level. JAMA. 1993;269:2386–91.PubMedCrossRef Crum RM, Anthony JC, Bassett SS, et al. Population-based norms for the Mini-Mental State Examination by age and educational level. JAMA. 1993;269:2386–91.PubMedCrossRef
26.
go back to reference Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982;17:37–49.PubMedCrossRef Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982;17:37–49.PubMedCrossRef
27.
go back to reference Mangoni AA, van Munster BC, Woodman RJ, et al. Measures of anticholinergic drug exposure, serum anticholinergic activity, and all-cause postdischarge mortality in older hospitalized patients with hip fractures. Am J Geriatr Psychiatry 2012;May 28. [Epub ahead of print]. Mangoni AA, van Munster BC, Woodman RJ, et al. Measures of anticholinergic drug exposure, serum anticholinergic activity, and all-cause postdischarge mortality in older hospitalized patients with hip fractures. Am J Geriatr Psychiatry 2012;May 28. [Epub ahead of print].
28.
go back to reference Flacker JM, Wei JY. Endogenous anticholinergic substances may exist during acute illness in elderly medical patients. J Gerontol A Biol Sci Med Sci. 2001;56:M353–5.PubMedCrossRef Flacker JM, Wei JY. Endogenous anticholinergic substances may exist during acute illness in elderly medical patients. J Gerontol A Biol Sci Med Sci. 2001;56:M353–5.PubMedCrossRef
29.
go back to reference Mulsant BH, Pollock BG, Kirshner M, et al. Serum anticholinergic activity in a community-based sample of older adults: relationship with cognitive performance. Arch Gen Psychiatry. 2003;60:198–203.PubMedCrossRef Mulsant BH, Pollock BG, Kirshner M, et al. Serum anticholinergic activity in a community-based sample of older adults: relationship with cognitive performance. Arch Gen Psychiatry. 2003;60:198–203.PubMedCrossRef
30.
go back to reference Rovner BW, David A, Lucas-Blaustein MJ, et al. Self-care capacity and anticholinergic drug levels in nursing home patients. Am J Psychiatry. 1988;145:107–9.PubMed Rovner BW, David A, Lucas-Blaustein MJ, et al. Self-care capacity and anticholinergic drug levels in nursing home patients. Am J Psychiatry. 1988;145:107–9.PubMed
31.
go back to reference Miller PS, Richardson JS, Jyu CA, et al. Association of low serum anticholinergic levels and cognitive impairment in elderly presurgical patients. Am J Psychiatry. 1988;145:342–5.PubMed Miller PS, Richardson JS, Jyu CA, et al. Association of low serum anticholinergic levels and cognitive impairment in elderly presurgical patients. Am J Psychiatry. 1988;145:342–5.PubMed
32.
go back to reference Wilson NM, Hilmer SN, March LM, et al. Associations between Drug Burden Index and falls in older people in residential aged care. J Am Geriatr Soc. 2011;59:875–80.PubMedCrossRef Wilson NM, Hilmer SN, March LM, et al. Associations between Drug Burden Index and falls in older people in residential aged care. J Am Geriatr Soc. 2011;59:875–80.PubMedCrossRef
33.
go back to reference Schor JD, Levkoff SE, Lipsitz LA, et al. Risk factors for delirium in hospitalized elderly. JAMA. 1992;267:827–31.PubMedCrossRef Schor JD, Levkoff SE, Lipsitz LA, et al. Risk factors for delirium in hospitalized elderly. JAMA. 1992;267:827–31.PubMedCrossRef
34.
go back to reference Tune LE, Damlouji NF, Holland A, et al. Association of postoperative delirium with raised serum levels of anticholinergic drugs. Lancet. 1981;2:651–3.PubMedCrossRef Tune LE, Damlouji NF, Holland A, et al. Association of postoperative delirium with raised serum levels of anticholinergic drugs. Lancet. 1981;2:651–3.PubMedCrossRef
35.
go back to reference Golinger RC, Peet T, Tune LE. Association of elevated plasma anticholinergic activity with delirium in surgical patients. Am J Psychiatry. 1987;144:1218–20.PubMed Golinger RC, Peet T, Tune LE. Association of elevated plasma anticholinergic activity with delirium in surgical patients. Am J Psychiatry. 1987;144:1218–20.PubMed
36.
go back to reference Chengappa KN, Pollock BG, Parepally H, et al. Anticholinergic differences among patients receiving standard clinical doses of olanzapine or clozapine. J Clin Psychopharmacol. 2000;20:311–6.PubMedCrossRef Chengappa KN, Pollock BG, Parepally H, et al. Anticholinergic differences among patients receiving standard clinical doses of olanzapine or clozapine. J Clin Psychopharmacol. 2000;20:311–6.PubMedCrossRef
37.
go back to reference Lechevallier-Michel N, Molimard M, Dartigues JF, et al. Drugs with anticholinergic properties and cognitive performance in the elderly: results from the PAQUID study. Br J Clin Pharmacol. 2005;59:143–51.PubMedCrossRef Lechevallier-Michel N, Molimard M, Dartigues JF, et al. Drugs with anticholinergic properties and cognitive performance in the elderly: results from the PAQUID study. Br J Clin Pharmacol. 2005;59:143–51.PubMedCrossRef
38.
go back to reference Gnjidic D, Bell JS, Hilmer SN, et al. Drug Burden Index associated with function in community-dwelling older people in Finland: a cross-sectional study. Ann Med. 2012;44:458–67.PubMedCrossRef Gnjidic D, Bell JS, Hilmer SN, et al. Drug Burden Index associated with function in community-dwelling older people in Finland: a cross-sectional study. Ann Med. 2012;44:458–67.PubMedCrossRef
39.
go back to reference Lönnroos E, Gnjidic D, Hilmer SN, et al. Drug Burden Index and hospitalization among community-dwelling older people. Drugs Aging. 2012;29:395–404.PubMedCrossRef Lönnroos E, Gnjidic D, Hilmer SN, et al. Drug Burden Index and hospitalization among community-dwelling older people. Drugs Aging. 2012;29:395–404.PubMedCrossRef
40.
go back to reference Abrams P, Andersson KE, Buccafusco JJ, et al. Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol. 2006;148:565–78.PubMedCrossRef Abrams P, Andersson KE, Buccafusco JJ, et al. Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol. 2006;148:565–78.PubMedCrossRef
41.
go back to reference Levey AI. Immunological localization of m1–m5 muscarinic acetylcholine receptors in peripheral tissues and brain. Life Sci. 1993;52:441–8.PubMedCrossRef Levey AI. Immunological localization of m1–m5 muscarinic acetylcholine receptors in peripheral tissues and brain. Life Sci. 1993;52:441–8.PubMedCrossRef
Metadata
Title
Anticholinergic Drug Use, Serum Anticholinergic Activity, and Adverse Drug Events Among Older People: A Population-Based Study
Authors
Pasi Lampela
Piia Lavikainen
J. Arturo Garcia-Horsman
J. Simon Bell
Risto Huupponen
Sirpa Hartikainen
Publication date
01-05-2013
Publisher
Springer International Publishing AG
Published in
Drugs & Aging / Issue 5/2013
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.1007/s40266-013-0063-2

Other articles of this Issue 5/2013

Drugs & Aging 5/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.