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Neostigmine: muscarinic effects

Side effects of anticholinesterases includebradycardia,hypotension,bronchospasm(and hypoxia), increasedrespiratory secretions,possiblynausea and vomiting (although this is controversial and, according to Miller (1), “Reports on the effect of anticholinesterase administration on postoperative nausea and vomiting are conflicting“),increased GI motility and secretions, miosis, anddecreased intraocular pressure.

Interestingly, excessive neostigminemay also lead to adepolarizingblock, similar to succinylcholine. According to Nair and Hunter, “neostigmine and other quaternary ammonium anticholinesterases have a direct action on skeletal muscle. Anticholinesterases increase the amount of acetylcholine released, by their effect on presynaptic receptors. In overdose, depolarization of the endplate caused by excess acetylcholine predominates and leads to depolarization block. The excess acetylcholine at the synapse also causes repeated stimulation of the receptors resulting in the decay time of the endplate potential being prolonged. This destroys the synchrony between endplate depolarization and the development of action potentials, leading to asynchronous excitation, and fibrillation and fasciculation of the muscle” (2). Additionally,animal studies have suggested that high doses of neostigminemayalso lead to adirect-action blockade of ACHr(3).

Anticholinesterase Side Effects

  • Cardiac: bradycardia, hypotension
  • Pulmonary: bronchospasm, hypoxia, increased secretions
  • GI: increased GI motility and secretions, PONV (controversial)
  • Eye: miosis, and decreased intraocular pressure
  • NMJ: in high doses may lead to a SCh-like blockade and possibly direct inhibition of ACHr


  1. J F Fiekers Concentration-dependent effects of neostigmine on the endplate acetylcholine receptor channel complex. J. Neurosci.: 1985, 5(2);502-14 Link

Other References

  1. Miller, RD et al. Miller’s Anesthesia, 7th ed, Churchill Livingstone: p 888-9. 2009 Link