Major
Established
Descrição
Diphenhydramine's potent anticholinergic effect directly opposes donepezil's pro-cholinergic mechanism, negating therapeutic benefit and increasing risk of delirium in elderly patients.
Mecanismo
Diphenhydramine is a potent muscarinic receptor antagonist; donepezil increases acetylcholine availability — direct pharmacodynamic antagonism completely negates donepezil's mechanism of action.
Significância Clínica
Concomitant use renders donepezil therapy futile and substantially raises delirium risk in dementia patients; both drugs appear on the Beers Criteria.
Conduta
Contraindicated in practical terms; use non-anticholinergic antihistamines (cetirizine, loratadine) in patients on cholinesterase inhibitors.