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Four of the five currently approved drugs available in the United States for the symptomatic improvement of Alzheimer's disease—tacrine, donepezil, rivastigmine, and galantamine—are cholinesterase inhibitors (Table 26–7). The use of tacrine is no longer recommended because of its potential hepatotoxic effects. The principal side effects of these medications are concentration dependent and result from their peripheral cholinergic actions. With these side effects in mind, clinicians should be aware of the drugs' specific pathways of elimination and potential pharmacokinetic drug interactions with CYP2D6 or CYP3A4 inhibitors and CYP3A4 inducers when prescribing donepezil and galantamine (Carrier 1999; Crismon 1998). Rivastigmine is affected by renal function, and FDA warnings have emphasized the need for careful dose titration (and retitration if restarting) to prevent severe vomiting. Drugs with potent anticholinergic effects directly antagonize cholinesterase inhibitors (Chew et al. 2005, 2008; Lu and Tune 2003; Mulsant et al. 2003).

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Table Reference Number
Table 26–7. Cholinesterase inhibitors

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