TITLE

Factors Associated with Serious Adverse Reactions to Cholinesterase Inhibitors

AUTHOR(S)
Pariente, Antoine; Joseph-Reinette Sanctussy, Dina; Miremont-Salamé, Ghada; Moore, Nicholas; Haramburu, Françoise; Fourrier-Réglat, Annie
PUB. DATE
January 2010
SOURCE
CNS Drugs;2010, Vol. 24 Issue 1, p55
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Cholinesterase inhibitors are used in Alzheimer's disease, mostly in elderly persons with co-morbidities and receiving co-medications that could increase the risk of serious adverse reactions. Objective: To identify factors associated with serious adverse drug reactions (ADRs) in patients treated with cholinesterase inhibitors. Methods: All ADRs associated with donepezil, rivastigmine or galantamine were identified in the French pharmacovigilance database, from the launching of these drugs to January 2007. Serious ADRs (SADRs) were those that led to death, hospitalization or prolongation of hospitalization, or that were life threatening. A multiple logistic regression analysis was used to identify factors associated with seriousness in the reported adverse reactions. Results: We identified 773 reports of ADRs related to cholinesterase inhibitor use, among which 438 (57%) concerned SADRs. The median age of patients was 80 years (interquartile range: 75-84 years); 65.1% were women. The most represented ADRs were those responsible for CNS disorders (17.0%), gastrointestinal disorders (16.2%) and cardiac rhythm disorders (11.2%). Factors associated with an increased risk of SADRs were: age (odds ratio [OR] 1.92; 95% CI 1.22, 3.02 for subjects aged 85 years and over), use of atypical antipsychotics (OR 2.15; 95% CI 1.04, 4.46), use of conventional antipsychotics (OR 2.06, 95%CI 1.10, 3.85), use of antihypertensive drugs (OR 2.11; 95%CI 1.47, 3.02) and use of drugs targeting the alimentary tract and metabolism (OR 1.62; 95% CI 1.06, 2.46). The use of benzodiazepines (long-acting or others), antidepressants (tricyclic or others) or antiarrhythmic drugs was not associated with the reporting of SADRs. Conclusions: An increased risk of SADRs related to cholinesterase inhibitors was associated with the use of antipsychotics (with no difference between conventional and atypical antipsychotics), drugs targeting the alimentary tract/metabolism and antihypertensive drugs. It was not associated with the use of other psychotropic drugs, other non-psychotropic CNS drugs or with the use of antiarrhythmic agents. The association with drugs targeting the alimentary tract and metabolism could result from a protopathic bias or reflect the particular sensitivity to serious nausea and vomiting in patients already treated for gastrointestinal disorders. These results confirm that attention needs to be paid to patients receiving both cholinesterase inhibitors and antipsychotics.
ACCESSION #
48314529

 

Related Articles

  • Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease. Di Lazzaro V; Oliviero A; Pilato F; Saturno E; Dileone M; Marra C; Daniele A; Ghirlanda S; Gainotti G; Tonali P A; Di Lazzaro, V; Oliviero, A; Pilato, F; Saturno, E; Dileone, M; Marra, C; Daniele, A; Ghirlanda, S; Gainotti, G; Tonali, P A // Journal of Neurology, Neurosurgery & Psychiatry;Apr2004, Vol. 75 Issue 4, p555 

    Objectives: Recent transcranial magnetic stimulation (TMS) studies demonstrate that motor cortex excitability is increased in Alzheimer's disease (AD) and that intracortical inhibitory phenomena are impaired. The aim of the present study was to determine whether hyperexcitability is...

  • Fixing Alzheimer Disease Trials by Improving Process and Methods. Schneider, Lon S. // Current Alzheimer Research;Oct2010, Vol. 7 Issue 7, p564 

    No abstract available.

  • An Overview on Natural Cholinesterase Inhibitors - A Multi-Targeted Drug Class - and Their Mass Production. Orhan, I. Erdogan; Orhan, G.; Gurkas, E. // Mini Reviews in Medicinal Chemistry;Sep2011, Vol. 11 Issue 10, p836 

    Cholinesterase enzyme family consisting of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) is important in pathogenesis of Alzheimer's disease (AD), explained by "cholinergic hypothesis". Accordingly, deficiency of the neuromediator called "acetylcholine" excessive amount of BChE has...

  • Scrutinizing the interactions of Cholinesterase Inhibitors with Amyloid Precursor Protein to Target Alzheimer's Disease. Runthala, Ashish; Rajamani, Mythili // Journal of Computational Intelligence in Bioinformatics;2010, Vol. 3 Issue 1, p31 

    Alzheimer's disease is a fatal brain disorder. It is progressive cognitive disease as it destroys neurons, causing problems with memory, behavior, and finally hampers work. The role of amyloid plaques in the disease is mostly about the β-amyloid protein, which is part of much larger protein...

  • Citations and Clinicians' Notes: Neurology and Psychiatry: Alzheimer's Disease and Other Dementias.  // Current Medical Literature: Health Care of Older People;2003, Vol. 16 Issue 3, p67 

    Presents citations and clinicians' notes concerning Alzheimer's disease and other dementias. Role of dietary and supplemental antioxidants in the primary prevention of Alzheimer's disease; Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional...

  • The Role of Bridging Studies in the Development of Cholinesterase Inhibitors for Alzheimer’s Disease. Cutler, N.R.; Sramek, J.J. // CNS Drugs;1998, Vol. 10 Issue 5, p355 

    The impairment of cognitive function that is seen in patients with Alzheimer’s disease is widely considered to be a consequence of cortical deficiencies in cholinergic transmission. Numerous cholinesterase inhibitors have been investigated for treatment of the disease, aiming to bolster...

  • Donepezil improves cognitive function in Alzheimer's patients.  // Geriatrics;Apr98, Vol. 53 Issue 4, p18 

    Focuses on the improvement in mental and physical function, by Alzheimer's disease (AD) patients on a regimen of the cholinesterase inhibitor donepezil HCI (Aricept). Description of Donepezil; Information on a study carried out; Results of the study; Comments from Dr. Lawrence Friedhoff, MD,...

  • Do cholinesterase inhibitors have disease-modifying effects in Alzheimer's disease? Giacobini, E. // CNS Drugs;2001, Vol. 15 Issue 2, p85 

    During the last decade, a systematic effort to develop a pharmacological treatment for Alzheimer disease (AD) has resulted in drugs being registered for the first time in the US and Europe for this specific indication. The 3 agents registered are cholinesterase inhibitors (ChEIs). The major...

  • Beyond Tacrine: Recently Developed Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease. Unni, L.K. // CNS Drugs;1998, Vol. 10 Issue 6, p447 

    Alzheimer's disease still remains a diagnosis of exclusion. Until treatment strategies aimed at targeting its underlying aetiology become available, a cholinergic approach appears to be the most promising treatment for improving cognition in this devastating disease. Research to date suggests...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics