Neostigmine methylsulfate

Actions

• An anticholinesterase agent which reversibly inhibits the hydrolysis of acetylcholine by competing with acetylcholine for attachment to acetylcholinesterase. As a result, acetylcholine accumulates at cholinergic synapses and its effects are prolonged and exaggerated.
  
• Produces a generalised cholinergic response, including miosis, increased tonus of intestinal and skeletal musculature, constriction of bronchi and ureters, bradycardia and stimulation of salivary and sweat glands.
  
• Used mainly for its direct cholinomimetic effect on skeletal muscle and to a lesser extent to increase the activity of smooth muscle.
• Because of its quaternary ammonium structure, neostigmine in moderate doses, does not cross the BBB to produce CNS effects. Extremely high doses, however, produce CNS stimulation followed by CNS depression.

Indications

• Reversal of the effects of neuromuscular blocking agents (e.g. tubocurarine, pancuronium).
  
• Prophylaxis and treatment of postoperative intestinal atony and urinary retention.
  
• Treatment of myasthenia gravis during acute exacerbations, when the condition is severe, or in neonates.

Pharmacokinetics

• For IV administration the elimination half-life is 47-60 minutes.
• For IM administration the elimination half-life is 50-91 minutes.
  
• Approximately 80% of a single IM dose of neostigmine is excreted in the urine in 24 hours, about 50% as unchanged drug and the remainder as metabolites.
  
• The major site of uptake is in the liver. It is metabolised partly by the hydrolysis of the ester linkage and partly by microsomal enzymes in the liver.