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cholinesterase inhibitor

Indications: - treatment of Alzheimer's disease (see Alzheimer agent) - some patients have subjective delay in worsening of cognitive impairment but many do not [11] - may reduce risk of age-related macular degeneration (RR=0.94) [13] * cholinesterase inhibitors improve MMSE scores 0.13 points/year & lower mortality (RR=0.73) [8] * galantamine is the only cholinesterase inhibitor reducing risk of severe dementia [8] Contraindications: - of no benefit for mild cognitive impairment [5] - bradycardia, sick sinus syndrome - syncope - diarrhea Adverse effects: (generalized cholinergic effects) 1) SLUDGE a) Salivation b) Lacrimation c) increased Urination & Defecation d) increased Gastrointestinal peristalsis e) Emesis (nausea/vomiting) 2) other a) miosis b) increased tone of skeletal & intestinal musculature - muscle spasms, leg cramps - diarrhea, bloat c) constriction of bronchi & ureters d) bradycardia e) stimulation of secretion by salivary & sweat glands f) confusion g) insomnia [1], abnormal dreams h) syncope, RR=1.76 [1,2,13] i) higher rates of permanent pacemaker insertion, HR=1.49 j) falls - hip fracture RR= 1.18 - deprescribing cholinesterase inhibitors in nursing home residents associated with lower risks for serious falls & fractures [6] - in patients with cognitive impairment, cholinesterase inhibitors reduce risk of falls [12] k) unintentional weight loss [4,9] - anorexia [11] l) rivastigmine (RR=1.1) & galantamine (RR=1.5) associated with increased risk of serious adverse events vs donepezil [10] Drug interactions: - anticholinergic agents may antagonize effects of cholinesterase inhibitors [2] Notes: - deprescribing cholinesterase inhibitors may result in worse cognitive, neuropsychiatric & functional status vs continuing treatment but certainty is low to very low [7] - deprescribing cholinesterase inhibitors in nursing home residents with advanced dementia not associated with negative outcomes [6]

Interactions

drug interactions drug adverse effects of cholinesterase inhibitors

Related

cholinesterase inhibitor clinical trials CNS cholinergic system pharmaceutical agents for treatment of Alzheimer's disease (Alzheimer's agent)

Specific

ambenonium (Mytelase) demecarium (Humorsol, Frumtosnil) donepezil (Aricept, Aricept ODT, Adlarity) edrophonium (Tensilon) galantamine (Reminyl, Razadyne, Nivalin) Huperzine A (Huperzia serrata, Fordine) latrepirdine (Dimebon, dimeboline, dimebolin) neostigmine (Prostigmin) phenserine physostigmine (Antilirium, Isopto Eserine) pilocarpine (Pilocar, Isopto Carpine, Salagen, Ocusert Pilo) pyridostigmine (Mestinon, Regnonol, Kalymin) rivastigmine (Exelon) tacrine; tetrahydroaminoacridine (Cognex, THA, Romotal) trichlorfon (Metrifonate)

General

enzyme inhibitor parasympathomimetic (cholinergic agent)

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 15, 17 American College of Physicians, Philadelphia 2009, 2016
  2. Boudreau DM et al. Concomitant use of cholinesterase inhibitors and anticholinergics: Prevalence and outcomes. J Am Geriatr Soc 2011 Nov; 59:2069 PMID: 22091958 - Johnell K, Fastbom J. Concurrent use of anticholinergic drugs and cholinesterase inhibitors: register-based study of over 700,000 elderly patients. Drugs Aging. 2008;25(10):871-7. PMID: 18808211
  3. Small G, Bullock R. Defining optimal treatment with cholinesterase inhibitors in Alzheimer's disease. Alzheimers Dement. 2011 Mar;7(2):177-84. Epub 2010 Nov 5. PMID: 21056013
  4. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  5. Russ TC, Morling JR. Cholinesterase inhibitors for mild cognitive impairment. Cochrane Database Syst Rev. 2012;9:CD009132 PMID: 22972133
  6. Niznik JD, Zhao X, He M et al. Risk for health events after deprescribing acetylcholinesterase inhibitors in nursing home residents with severe dementia. J Am Geriatr Soc 2020 Apr; 68:699-707 PMID: 31769507 https://onlinelibrary.wiley.com/doi/abs/10.1111/jgs.16241
  7. Parsons C, Lim WY, Loy C et al Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia. Cochrane Database of Systematic Reviews. 2021. Feb 3. Not indexed in PubMed https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009081.pub2/full
  8. Xu H, Garcia-Ptacek S, Jonsson L et al. Long-term effects of cholinesterase inhibitors on cognitive decline and mortality. Neurology 2021 Apr 27; 96:e2220 PMID: 33741639 PMCID: PMC8166426 Free PMC article https://n.neurology.org/content/96/17/e2220
  9. Soysal P, Isik AT, Stubbs B et al. Acetylcholinesterase inhibitors are associated with weight loss in older people with dementia: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2016 Dec;87(12):1368-1374 PMID: 27261502 https://jnnp.bmj.com/content/87/12/1368
  10. Masurkar PP, Chatterjee S, Sherer JT et al. Risk of Serious Adverse Events Associated With Individual Cholinesterase Inhibitors Use in Older Adults With Dementia: A Population-Based Cohort Study. Drugs Aging 2022. June 6 PMID: 35666463 https://link.springer.com/article/10.1007/s40266-022-00944-z
  11. NEJM Knowledge+ Psychiatry
  12. Ahuja M, Siddhpuria S, Karimi A et al. Cholinesterase inhibitors and falls, syncope and injuries in patients with cognitive impairment: a systematic review and meta-analysis. Age Ageing. 2023 Nov 2;52(11):afad205 PMID: 37993407
  13. Sutton SS, Magagnoli J, Cummings TH et al Alzheimer Disease Treatment With Acetylcholinesterase Inhibitors and Incident Age-Related Macular Degeneration. JAMA Ophthalmol. Published online January 4, 2024. PMID: 38175625 PMCID: PMC10767642 Free PMC article. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2813353