PMID- 24944370
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140619
LR  - 20220311
IS  - 0011-393X (Print)
IS  - 0011-393X (Linking)
VI  - 64
IP  - 4
DP  - 2003 Apr
TI  - Cholinesterase inhibitors for the treatment of Alzheimer's disease:: getting on 
      and staying on.
PG  - 216-35
LID - 10.1016/S0011-393X(03)00059-6 [doi]
AB  - BACKGROUND: Cholinesterase (ChE) inhibitors currently used in the treatment of 
      Alzheimer's disease (AD) are the acetylcholinesterase (AChE)-selective 
      inhibitors, donepezil and galantamine, and the dual AChE and 
      butyrylcholinesterase (BuChE) inhibitor, rivastigmine. In addition to differences 
      in selectivity for AChE and BuChE, ChE inhibitors also differ in pharmacokinetic 
      and pharmacodynamic properties, and these differences could significantly impact 
      on safety, tolerability, and efficacy. OBJECTIVE: The aim of this article was to 
      provide an overview of the ChE inhibitors widely used in AD, focusing on key 
      pharmacologic differences among agents and how these may translate into important 
      differences in safety, tolerability, and efficacy in clinical practice. METHODS: 
      Using published literature collected over time by the author, a review was 
      conducted, focusing on the pharmacology and clinical data of donepezil, 
      galantamine, and rivastigmine. RESULTS: All ChE inhibitors have the potential to 
      induce centrally mediated cholinergic adverse events (AEs), such as nausea and 
      vomiting, if the dose is increased too rapidly or in increments that are too 
      large. These AEs, which are most likely to occur during the "getting on," or 
      dose-escalation, phase of treatment, may result in patients discontinuing 
      treatment early without achieving optimum therapeutic benefit. To reduce the 
      incidence of these AEs, a slow dose-escalation schedule has been established in 
      clinical practice, consisting of a "start low, go slow" procedure with a minimum 
      of 4 weeks between dose increases. After "getting on" treatment, maintaining 
      treatment in the long term, or "staying on," may be achieved with good safety, 
      tolerability, and sustained symptomatic efficacy across the key symptom domains 
      (activities of daily living, behavior, and cognition). CONCLUSIONS: ChE 
      inhibitors provide symptomatic benefit in AD across key symptom domains. Factors 
      influencing the safety, tolerability, and efficacy of these agents in clinical 
      practice include ChE enzymes inhibited, brain and brain-region ChE selectivity, 
      and metabolism route. Class-specific cholinergic AEs can be minimized using slow, 
      flexible dose escalation.
FAU - Grossberg, George T
AU  - Grossberg GT
AD  - Department of Psychiatry, St. Louis University School of Medicine, St. Louis, 
      Missouri, MO, USA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Curr Ther Res Clin Exp
JT  - Current therapeutic research, clinical and experimental
JID - 0372621
PMC - PMC4052996
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - acetylcholinesterase
OT  - butyrylcholinesterase
OT  - cholinesterase inhibitors
OT  - safety and tolerability
EDAT- 2003/04/01 00:00
MHDA- 2003/04/01 00:01
PMCR- 2003/04/01
CRDT- 2014/06/20 06:00
PHST- 2003/02/13 00:00 [accepted]
PHST- 2014/06/20 06:00 [entrez]
PHST- 2003/04/01 00:00 [pubmed]
PHST- 2003/04/01 00:01 [medline]
PHST- 2003/04/01 00:00 [pmc-release]
AID - S0011-393X(03)00059-6 [pii]
AID - 10.1016/S0011-393X(03)00059-6 [doi]
PST - ppublish
SO  - Curr Ther Res Clin Exp. 2003 Apr;64(4):216-35. doi: 
      10.1016/S0011-393X(03)00059-6.