Cholinesterase inhibitors for the treatment of Alzheimer's disease:: getting on and staying on.

摘要: Background: Cholinesterase (ChE) inhibitors currently used in the treatment of Alzheimer's disease (AD) are acetylcholinesterase (AChE)-selective inhibitors, donepezil and galantamine, dual AChE butyrylcholinesterase (BuChE) inhibitor, rivastigmine. In addition to differences selectivity for BuChE, ChE also differ pharmacokinetic pharmacodynamic properties, these could significantly impact on safety, tolerability, efficacy. Objective: The aim this article was provide an overview widely AD, focusing key pharmacologic among agents how may translate into important efficacy clinical practice. Methods: Using published literature collected over time by author, a review conducted, pharmacology data donepezil, rivastigmine. Results: All have potential induce centrally mediated cholinergic adverse events (AEs), such as nausea vomiting, if dose is increased too rapidly or increments that large. These AEs, which most likely occur during “getting on,” dose-escalation, phase treatment, result patients discontinuing early without achieving optimum therapeutic benefit. To reduce incidence slow dose-escalation schedule has been established practice, consisting “start low, go slow” procedure with minimum 4 weeks between increases. After on” maintaining long term, “staying be achieved good sustained symptomatic across symptom domains (activities daily living, behavior, cognition). Conclusions: benefit AD domains. Factors influencing practice include enzymes inhibited, brain brain-region selectivity, metabolism route. Class-specific AEs can minimized using slow, flexible escalation.