Donepezil

Donepezil is a piperidine ChE inhibitor, which rever-sibly and noncompetitively inhibits centrally active acetylcholinesterase.35

Donepezil is approved for the treatment of dementia of the Alzheimer's type at a dose of 5 mg/day. This dose should be increased to 10 mg/day if needed after 4 to 6 weeks. Efficacy has been demonstrated in patients with mild-to-moderate and -severe AD. Table 35-5 describes the dosing strategies for all of the approved agents for AD.35-39

Adverse reactions with donepezil include nausea, vomiting, and diarrhea. Table 35-6 compares the major side effects for all of the approved agents for AD.35-39

Only a small number of drug interactions have been reported with donepezil. In vitro studies show a low rate of binding of donepezil to cytochrome P450 (CYP)3A4 or 2D6. Whether donepezil has the potential for enzyme induction is not known. Monitoring for possible increased peripheral side effects is advised when adding a

CYP2D6 or 3A3/4 inhibitor to donepezil treatment. Also, inducers of CYP2D6 and

3A4 could increase the rate of elimination of donepezil. Rivastigmine

© Rivastigmine has central activity for both the acetylcholinesterase and bu-

tyrylcholinesterase enzymes. Acetylcholinesterase is found in two forms: globular 4 and globular 1. In postmortem studies, globular 4 is significantly depleted, while globular 1 is still abundant. Thus, blocking metabolism of globular 1 may lead to higher concentrations of Ach. Rivastigmine has higher activity at globular 1 than at globular 4. Theoretically this may be advantageous, as rivastigmine prevents the degradation of Ach via the acetylcholinesterase globular 1 over the course of the disease as compared to the other ChE inhibitors.

The dual inhibition of acetylcholinesterase and butyrylcholinesterase may lead to broader efficacy. As acetyl-cholinesterase activity decreases with disease progression, the acetylcholinesterase-selective agents may lose their effect, while the dual inhibitors may still be effective due to the added inhibition of butyrylcholinesterase. However, this has not been demonstrated clinically.

Cognitive Treatment

Patient diagnosed with AO according to NiNCOS-ADflOA cntena

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