RT Book, Section A1 Howland, Mary Ann A2 Nelson, Lewis S. A2 Howland, Mary Ann A2 Lewin, Neal A. A2 Smith, Silas W. A2 Goldfrank, Lewis R. A2 Hoffman, Robert S. SR Print(0) ID 1163002216 T1 Physostigmine Salicylate T2 Goldfrank's Toxicologic Emergencies, 11e YR 2019 FD 2019 PB McGraw-Hill Education PP New York, NY SN 9781259859618 LK accessemergencymedicine.mhmedical.com/content.aspx?aid=1163002216 RD 2024/03/28 AB Physostigmine is a carbamate that reversibly inhibits cholinesterases in both the peripheral and central nervous system (CNS).60 The tertiary amine structure of physostigmine permits CNS penetration and differentiates it from neostigmine and pyridostigmine, which are quaternary amines that have limited ability to enter the CNS. The inhibition of cholinesterases prevents the metabolism of acetylcholine, allowing acetylcholine to accumulate and antagonize the antimuscarinic effects of xenobiotics such as atropine, scopolamine, and diphenhydramine.23,43,72 Although physostigmine previously was used as an antagonist to the antimuscarinic effects of cyclic antidepressants and phenothiazines, we currently recommend against this use because of a poor risk-to-benefit ratio, and the potential for exacerbation of life-threatening cardiotoxicity. Similarly, physostigmine has a poor risk-to-­benefit ratio in the management of presumed γ-hydroxybutyric acid (GHB) and baclofen toxicity.5,49,63,73 Atypical antipsychotics have complex pharmacologic effects. Although some atypical antipsychotics, such as quetiapine and olanzapine, have significant antimuscarinic side effects, the benefit of treating these anticholinergic effects with physostigmine must be weighed against the potential risks of exacerbating cardiotoxicity.10,25,61,70