In addition to atropine and other muscarinic agents, phenothiazines, antihistamines, and tricyclic antidepressants have central and peripheral anticholinergic activity. The effectiveness of physostigmine in reversing the anticholinergic effects of these agents has been documented. However, other toxic effects of the tricyclic antidepressants and phenothiazines (see Chapters 17 and 18), such as intraventricular conduction deficits and ventricular arrhythmias, are not reversed by physostigmine. In addition, physostigmine may precipitate seizures; hence, its usually small potential benefit must be weighed against this risk. The initial intravenous or intramuscular dose of physostigmine is 2 mg, with additional doses given as necessary. Physostigmine, a tertiary amine, crosses the blood-brain barrier, in contrast to the quaternary anti-AChE drugs.
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