neostigmine

neostigmine, drug used to mimic the effects of stimulation of the parasympathetic nervous system. Along with several other drugs that have a similar mode of action, it inhibits the action of the enzyme cholinesterase, which destroys the substance acetylcholine at nerve endings. Because neostigmine increases the effective concentration of acetylcholine, it causes such body changes as contraction of the pupils, increased activity of intestinal muscles, and increased secretion by the salivary and sweat glands. It will cause menstrual bleeding in a nonpregnant woman whose menstrual period is delayed, and it is therefore used as a pregnancy test. Neostigmine and related drugs are also used to diagnose and control the neuromuscular disease myasthenia gravis. Because neostigmine causes decreased fluid pressure in the eye it is used to treat certain types of glaucoma. The drug atropine is sometimes given along with neostigmine to prevent the latter's side effects. Ephedrine often enhances the action of neostigmine.

Neostigmine is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor.

Neostigmine is available under several trade names such as Prostigmin.

Neostigmine was first synthesized by Aeschlimann and Reinert in 1931.

Pharmacology

By interfering with the breakdown of acetylcholine, neostigmine indirectly stimulates both nicotinic and muscarinic receptors. Unlike physostigmine, neostigmine has a qurternary nitrogen; hence, it is more polar and does not enter the CNS. its effect on skeletal muscle is greater than that of physostigmine, and it can stimulate contractility before it paralyzes. Neostigmine has moderate duration of action, usually thirty minutes to two hours. Neostigmine binds to the anionic site of cholinesterase. The drug blocks the active site of acetylcholinesterase so the enzyme can no longer break down the acetylcholine molecules before they reach the postsynaptic membrane receptors. This allows for the threshold to be reached so a new impulse can be triggered in the next neuron. In myasthenia gravis there are too few acetylcholine receptors so with the acetylcholinesterase blocked, acetylcholine can bind to the few receptors and trigger a muscular contraction.

Clinical Uses

It is used to improve muscle tone in people with myasthenia gravis and routinely, in anesthesia at the end of an operation, to reverse the effects of non-depolarizing muscle relaxants such as rocuronium and vecuronium.

It can also be used for urinary retention resulting from general anaesthesia and to treat curariform drug toxicity.

Another indication for use is the Ogilvie syndrome which is a pseudoobstruction of the colon in critically ill patients.

Neostigmine will cause slowing of the heart rate (bradycardia), for this reason it is usually given along with a parasympatholytic drug such as atropine or glycopyrrolate.

Though only one of two treatments available for Myasthenia Gravis this drug is no longer available to anyone using the Medicare Part D program.

References

Sources

• Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
• Canadian Pharmacists Association (2000). Compendium of Pharmaceuticals and Specialties (25th ed.). Toronto, ON: Webcom. ISBN 0-919115-76-4