PHARMACOLOGY AND CLINICAL EFFICACY OF CHOLINESTERASE-INHIBITORS

The pharmacology and clinical efficacy of cholinesterase inhibitors (C hEIs) in patients with Alzheimer's disease (AD) are discussed. ChEIs c an be classified pharmacologically on the basis of the duration of cho linesterase inhibition. The duration of inhibition is short for tacrin e and donepezil, intermediate for rivastigmine, and long for metrifona te, Pharmacokinetic differences also distinguish ChEIs. The two instru ments that are most accepted for use in evaluating the efficacy of dru gs for AD are the Alzheimer's Disease Assessment Scale-Cognitive Porti on (ADAS-Cog) and the Clinician's Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus). In clinical trials, all ChEIs have produced improvements in the cognitive deficits seen in patients with AD, and some have also improved behavioral problems and increased pat ients' ability to perform activities of daily living. Only donepezil a nd metrifonate are administered once daily. Except for metrifonate, th e dosage of each drug should be adjusted upward over several weeks to minimize adverse effects. Hepatotoxicity, the most important adverse e ffect of tacrine, has not been observed with other ChEIs. Tacrine and donepezil have the potential to interact with other drugs that depend on the same metabolic pathways. Although ChEIs generally improve cogni tion in patients with AD, differences among these medications are subs tantial in some cases and should be thoroughly considered by clinician s.