neostigmine
Brand: Prostigmin, Bloxiverz
Prototype: donepezil
Drug Class: cholinesterase inhibitor
Drug Family: antidementia
Subclass: reversible acetylcholinesterase inhibitor
Organ Systems: cnsmusculoskeletal
Mechanism of Action
Reversibly inhibits acetylcholinesterase at the NMJ, increasing acetylcholine concentration and overcoming competitive NMBA blockade. Does not cross the BBB (quaternary ammonium). Must be co-administered with anticholinergic (glycopyrrolate or atropine) to counter muscarinic side effects.
acetylcholinesterase (AChE)
Indications
- reversal of non-depolarizing NMBA (moderate depth)
- myasthenia gravis (symptomatic treatment)
- postoperative ileus
- urinary retention
Contraindications
- peritonitis
- mechanical urinary or GI obstruction
- succinylcholine blockade (worsens)
Adverse Effects
Common
- bradycardia
- nausea
- vomiting
- increased secretions
- bronchoconstriction
Serious
- severe bradycardia and heart block without anticholinergic pre-treatment
- cholinergic crisis
Pharmacokinetics (ADME)
| Absorption | IV for anesthesia; oral for myasthenia gravis |
| Distribution | minimal CNS penetration (quaternary ammonium) |
| Metabolism | hydrolysis by cholinesterases and hepatic degradation |
| Excretion | renal |
| Half-life | 1-2 hours |
| Onset | IV: 1-20 minutes |
| Peak | 7-10 minutes IV |
| Duration | 1-2 hours |
| Protein Binding | minimal |
| Vd | 0.8 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| anticholinergics (glycopyrrolate, atropine) | counter muscarinic side effects; must be co-administered | beneficial |
| succinylcholine | potentiates and prolongs depolarizing blockade by inhibiting plasma cholinesterase | major |
Nursing Considerations
- Always administer glycopyrrolate 0.2 mg per 1 mg neostigmine (or atropine) to prevent bradycardia, bronchospasm, and hypersalivation.
- Use only when TOF ratio >0.25 (at least 2 twitches); reversal at deeper blockade is unreliable and risks residual paralysis.
- In myasthenia gravis, too much neostigmine causes cholinergic crisis (weakness, secretions, bradycardia) which can mimic myasthenic crisis — distinguish by the edrophonium test.
- Sugammadex has replaced neostigmine for rocuronium/vecuronium reversal in many settings; neostigmine remains relevant for other NMBAs and myasthenia gravis.
Clinical Pearls
- Neostigmine does not cross the BBB (quaternary ammonium) making it safer than physostigmine for NMJ reversal without CNS stimulation risk.
- Incomplete reversal with neostigmine is a leading cause of postoperative respiratory complications; quantitative TOF monitoring confirming ratio >0.9 is required before extubation.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.