neostigmine

Neostigmine is a reversible inhibitor of acetylcholinesterase, a quaternary ammonium compound that increases acetylcholine at cholinergic synapses. Its charged nature limits penetration of the central nervous system, so its actions are predominantly peripheral. It is used to treat myasthenia gravis and to reverse nondepolarizing neuromuscular blockade after anesthesia. It is also employed for postoperative ileus and urinary retention due to bowel or bladder atony in some settings.

Mechanism and pharmacokinetics: By inhibiting acetylcholinesterase, neostigmine raises acetylcholine concentration at the neuromuscular junction and at autonomic synapses, enhancing skeletal muscle contraction and parasympathetic activity. Onset after intravenous administration is typically within minutes, with a duration of action of up to a few hours. Because muscarinic stimulation can produce undesirable effects, neostigmine is commonly given with an antimuscarinic agent such as atropine or glycopyrrolate to limit bradycardia, bronchorrhea, and other parasympathetic effects. It can be administered orally or parenterally.

Adverse effects and contraindications: The most common adverse effects are cholinergic symptoms, including bradycardia, increased salivation, bronchial secretions, sweating, and gastrointestinal cramps. Bronchospasm or hypotension can occur, particularly in susceptible patients or with concomitant cholinergic drugs. Neostigmine should be used with caution in individuals with peptic ulcers, asthma, bradyarrhythmias, or intestinal or urinary obstruction. Overdose is treated with antimuscarinic agents such as atropine or glycopyrrolate.

Clinical uses in more detail: In myasthenia gravis, neostigmine improves muscle strength by enhancing neuromuscular transmission. In anesthesia, it is used to reverse residual nondepolarizing neuromuscular blockade after surgery. It may also be used for postoperative ileus and urinary retention due to atony in some cases, though others may prefer alternative therapies. It is not effective against depolarizing neuromuscular blockers such as succinylcholine and may prolong their effects if used inappropriately.