Cholinesterase Inhibitors | NMDA Receptor Antagonist
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).