Rockwood_2011_Am.J.Geriatr.Pharmacother_9_80

BACKGROUND: Older adults are susceptible to a variety of illnesses, many of which can be treated with medications that may need to be used for the long term. Considerable attention has been paid to drugs that, in addition to their intended function, may have an anticholinergic effect that results in undesirable side effects, including impairment in cognition. Cholinesterase inhibitors are used as procholinergic drugs to improve cognitive dysfunction in Alzheimer's disease. We hypothesized that some of the drugs commonly used by older adults might, in addition to their intended function, also have procholinergic effects by virtue of inhibiting cholinesterases. OBJECTIVE: To determine the potential procholinergic nature of some of the commonly used drugs by examining their cholinesterase inhibiting properties. METHODS: The Ellman spectrophotometric method was used with human acetylcholinesterase and butyrylcholinesterase, in the absence and presence of increasing concentrations of each test drug. To compare inhibition potencies, from enzyme kinetic data, we determined half maximal inhibitory concentration (IC(50) values) for each cholinesterase by each drug. RESULTS: Of the 28 drugs examined, over half (17/28) inhibited one or both of the human cholinesterases. The inhibition potencies were often within 1 to 2 orders of magnitude of reversible cholinesterase inhibitors currently used to treat Alzheimer's disease. These included trazodone, quetiapine, risperidone, indapamide, and perindopril. CONCLUSIONS: Many drugs used by older adults for other reasons have potentially clinically relevant procholinergic effects. The effect of cumulative cholinesterase inhibition merits clinical evaluation.