Neostigmine

Class	Acetylcholinesterase inhibitor
Chemistry	Quaternary ammonium compound
Routes of administration	IV or oral
Absorption	Poor absorption and high firsty pass metabolism; minimal oral bioavailability (less than 5%)
Solubility	pKa=12.0; good water solubility, minimal lipid solubility
Distribution	VOD=0.12 L/kg; 15-25% protein-bound
Metabolism	Slowly hydrolysed by acetylcholinesterase and also by non-specific plasma esterases
Elimination	About 70% is eliminated in the urine unchanged
Time course of action	Half-life ~70 minutes, duration of action 20-30 minutes
Target receptor	Acetylcholinesterase
Mechanism of action	By binding to acetylcholinesterase, neostigmine acts as a competing substrate, replacing acetylcholine and decreasing acetylcholinesterase activity. The drug is metabolised much more slowly than acetylcholine, which means the enzyme is blocked for a sustained period.
Clinical effects	Reversal of neuromuscular junction blockade (by nondepolarising agents). Also, in high doses, can cause depolarising neuromuscular blockade on its own. A ceiling effect reduces its efficacy as a NMJ blocker reversal agent. Has many cholinergic side effects, including salivation, bronchorrhoea, bradycardia, lacrimation, urinary incontinence and diarrhoea
Literature reference	Calvey et al (1979)
CICM details of understanding	Level 2
Mentioned around Deranged Physiology	Cholinergic drugs and acetylcholinesterase inhibitors. Follows into Effects of acetylcholine receptor activation.
Related SAQs