Cholinesterase inhibitors (ChEIs) are used to palliate cholinergic deficiency. All 4 currently approved ChEIs (ie, donepezil, rivastigmine, galantamine) inhibit acetylcholinesterase (AChE) at the synapse (specific cholinesterase).
Rivastigmine also inhibits butyrylcholinesterase (BuChE). Although BuChE levels may be increased in AD, it is not clear that rivastigmine has greater clinical efficacy than donepezil and galantamine.
Galantamine has a different second mechanism of action; it is also a presynaptic nicotinic modulator. No data exist to indicate that this second mechanism is of clinical importance.
Donepezil (Aricept, Aricept ODT)
Donepezil is indicated for the treatment of dementia of the Alzheimer type. Donepezil has shown efficacy in patients with mild to moderate AD, as well as moderate to severe AD. It selectively inhibits acetylcholinesterase, the enzyme responsible for the destruction of acetylcholine, and improves the availability of acetylcholine. Donepezil's long half-life provides a long duration of drug availability for binding at the receptor sites. There is no evidence to suggest that the underlying disease process of dementia is affected by administration of donepezil.
Dosing recommendations for mild to moderate AD are 5-10 mg given once daily. Patients with moderate to severe AD can
be given 10 or 23 mg once daily.
Rivastigmine (Exelon, Exelon Patch)
Rivastigmine PO is indicated for the treatment of mild to moderate dementia of the Alzheimer type. Initial dosing recommendations are 1.5 mg PO BID, with a maximum dose of 12 mg/day PO. Rivastigmine is a potent, selective inhibitor of brain AChE and BChE. Rivastigmine is considered a pseudo-irreversible inhibitor of AChE.
While the precise mechanism of rivastigmine's action is unknown, it is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase.
The transdermal patch 13.3 mg/24 h is approved for all stages of Alzheimer disease, including severe. Dose titration is needed when initiating.
Galantamine (Razadyne, Razadyne ER)
Galantamine is indicated for the treatment of mild to moderate dementia of the Alzheimer type. It enhances central cholinergic function and likely inhibits AChE. There is no evidence that galantamine alters the course of the underlying dementing process. The dosing recommendation for the immediate-release formulation is 4 mg twice daily. The extended-release formulation is given at a dose of 8 mg once daily. The maintenance dose after dose titration is 16-24 mg/day.