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

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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.

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References

  1. 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.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  PubMed  Google Scholar 

  3. 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.

    Article  PubMed  Google Scholar 

  4. 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.

    Article  PubMed  CAS  Google Scholar 

  5. Flynn RA, Glynn DA, Kennedy MP. Anticholinergic treatment in airways diseases. Adv Ther. 2009;26:908–19.

    Article  PubMed  CAS  Google Scholar 

  6. 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.

    Article  PubMed  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    Article  PubMed  CAS  Google Scholar 

  9. Farrall AJ, Wardlaw JM. Blood-brain barrier: ageing and microvascular disease–systematic review and meta-analysis. Neurobiol Aging. 2009;30:337–52.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. 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.

    Article  PubMed  CAS  Google Scholar 

  12. Tune L, Coyle JT. Serum levels of anticholinergic drugs in treatment of acute extrapyramidal side effects. Arch Gen Psychiatry. 1980;37:293–7.

    Article  PubMed  CAS  Google Scholar 

  13. 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  CAS  Google Scholar 

  14. 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.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. 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.

    Article  PubMed  Google Scholar 

  17. 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.

    Article  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. Penttilä J, Scheinin H, Syvälahti E. Measurement of anticholinergic effects of psychotropic drugs in humans. Pharmacopsychiatry. 2005;38:187–93.

    Article  PubMed  Google Scholar 

  20. 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.

    Article  PubMed  Google Scholar 

  21. 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.

    Article  PubMed  Google Scholar 

  22. 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.

    Article  PubMed  Google Scholar 

  23. 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.

    Article  PubMed  Google Scholar 

  24. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9:179–86.

    Article  PubMed  CAS  Google Scholar 

  25. 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.

    Article  PubMed  CAS  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. 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. 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.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  CAS  Google Scholar 

  30. 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  CAS  Google Scholar 

  31. 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  CAS  Google Scholar 

  32. 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.

    Article  PubMed  Google Scholar 

  33. Schor JD, Levkoff SE, Lipsitz LA, et al. Risk factors for delirium in hospitalized elderly. JAMA. 1992;267:827–31.

    Article  PubMed  CAS  Google Scholar 

  34. Tune LE, Damlouji NF, Holland A, et al. Association of postoperative delirium with raised serum levels of anticholinergic drugs. Lancet. 1981;2:651–3.

    Article  PubMed  CAS  Google Scholar 

  35. 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  CAS  Google Scholar 

  36. 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.

    Article  PubMed  CAS  Google Scholar 

  37. 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.

    Article  PubMed  Google Scholar 

  38. 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.

    Article  PubMed  CAS  Google Scholar 

  39. Lönnroos E, Gnjidic D, Hilmer SN, et al. Drug Burden Index and hospitalization among community-dwelling older people. Drugs Aging. 2012;29:395–404.

    Article  PubMed  Google Scholar 

  40. 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.

    Article  PubMed  CAS  Google Scholar 

  41. Levey AI. Immunological localization of m1–m5 muscarinic acetylcholine receptors in peripheral tissues and brain. Life Sci. 1993;52:441–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Hannele Jaatinen and Pirjo Hänninen for technical help in SAA analysis. The authors declare that they have no conflict of interest. This study was supported by the Social Insurance Institution of Finland (data collection and analysis) and City of Kuopio (data collection). The authors have no conflicts of interest relevant to the results of this manuscript.

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Authors and Affiliations

  1. Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, 70211, Kuopio, Finland

    Pasi Lampela, Piia Lavikainen, J. Simon Bell & Sirpa Hartikainen

  2. Clinical Pharmacology and Geriatric Pharmacotherapy Unit, School of Pharmacy, University of Eastern Finland, Kuopio, Finland

    Pasi Lampela, J. Simon Bell & Sirpa Hartikainen

  3. Department of Geriatrics, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland

    Piia Lavikainen

  4. Division of Pharmacology and Toxicology, University of Helsinki, Helsinki, Finland

    J. Arturo Garcia-Horsman

  5. Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia

    J. Simon Bell

  6. Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland

    Risto Huupponen

  7. Clinical Pharmacology Unit, Turku University Hospital, Turku, Finland

    Risto Huupponen

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  1. Pasi Lampela
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  2. Piia Lavikainen
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  3. J. Arturo Garcia-Horsman
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  6. Sirpa Hartikainen
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Correspondence to Pasi Lampela.

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Lampela, P., Lavikainen, P., Garcia-Horsman, J.A. et al. Anticholinergic Drug Use, Serum Anticholinergic Activity, and Adverse Drug Events Among Older People: A Population-Based Study. Drugs Aging 30, 321–330 (2013). https://doi.org/10.1007/s40266-013-0063-2

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  • DOI: https://doi.org/10.1007/s40266-013-0063-2

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