Physostigmine and Neostigmine
Pharmacology. Physostigmine and neostigmine are carbamates and reversible inhibitors of acetylcholinesterase, the enzyme that degrades acetylcholine. They increase concentrations of acetylcholine, causing stimulation of both muscarinic and nicotinic receptors. The tertiary amine structure of physostigmine allows it to penetrate the blood-brain barrier and exert central cholinergic effects as well. Neostigmine, a quaternary ammonium compound, is unable to penetrate the CNS. Owing to cholinergic stimulation of the reticular activating system of the brainstem, physostigmine has nonspecific analeptic (arousal) effects. After parenteral administration of physostigmine, the onset of action is within 3–8 minutes and the duration of effect is usually 30–90 minutes. The elimination half-life is 15–40 minutes. Neostigmine has a slower onset of 7–11 minutes and a longer duration of effect of 60–120 minutes.
Indications
Physostigmine is used for the management of severe anticholinergic syndrome (agitated delirium, urinary retention, severe sinus tachycardia, or hyperthermia with absent sweating) from antimuscarinic agents (eg, benztropine, atropine, jimson weed [Datura], diphenhydramine). The typical indication is for reversal of agitated delirium in patients requiring physical and/or chemical restraints. For a discussion of anticholinergic toxicity, see Anticholinergics. Although there are anecdotal case reports of the use of physostigmine to treat delirium and coma associated with gamma-hydroxybutyrate (GHB), baclofen, and several atypical antipsychotic (olanzapine, clozapine, quetiapine) agents, its safety and efficacy are uncertain with these intoxications.
Physostigmine is sometimes used diagnostically to differentiate functional psychosis from anticholinergic delirium.
Neostigmine is used primarily to reverse the effect of nondepolarizing neuromuscular blocking agents.
Contraindications
Physostigmine should not
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