Mechanism of action of Nostigmine and Uses

Mechanism of Action of Neostigmine:

Neostigmine is an acetylcholinesterase inhibitor. It inhibits the enzyme acetylcholinesterase (AChE), which is responsible for breaking down acetylcholine (ACh) at the neuromuscular junction. By inhibiting AChE, neostigmine increases the concentration of acetylcholine in the synaptic cleft, thereby enhancing cholinergic transmission.

1. Normal Synaptic Transmission:

   • ACh release: Acetylcholine is released from the nerve terminal and binds to nicotinic receptors on the muscle cell membrane, triggering muscle contraction.
   • AChE action: Acetylcholinesterase breaks down ACh into choline and acetate, terminating its action and allowing the muscle to relax.

2. With Neostigmine:

   • AChE inhibition: Neostigmine inhibits AChE, preventing the breakdown of acetylcholine.
   • Increased ACh: As a result, acetylcholine accumulates in the synapse, prolonging its action on nicotinic and muscarinic receptors.
   • Enhanced muscle contraction: This increases the chances of stimulating nicotinic receptors on muscle cells, leading to prolonged muscle contractions.

Chemical Reactions:

In terms of chemical reactions, the process can be simplified:

1. Without Neostigmine:
   Acetylcholine (ACh) + Acetylcholinesterase (AChE) → Choline + Acetate
   (Acetylcholine is broken down)

2. With Neostigmine:
   Neostigmine binds to AChE, inhibiting its function, so:
   Acetylcholine (ACh) → remains active at the receptor, leading to prolonged effect.

Uses of Neostigmine:

1. Treatment of Myasthenia Gravis:
   Myasthenia gravis is an autoimmune disease where antibodies block, alter, or destroy nicotinic acetylcholine receptors at the neuromuscular junction. Neostigmine improves muscle strength by increasing ACh levels.

2. Reversal of Non-Depolarizing Neuromuscular Blockade:
   After surgery, non-depolarizing muscle relaxants (e.g., vecuronium) are used to induce paralysis. Neostigmine is given to reverse this paralysis by increasing ACh levels, which competes with the muscle relaxant at the receptor site.

3. Postoperative Urinary Retention and Abdominal Distension:
   Neostigmine can stimulate smooth muscle contractions, helping to treat urinary retention or bowel immobility.

4. Antidote for Anticholinergic Poisoning:
   Neostigmine may be used to counteract the effects of anticholinergic toxicity by enhancing cholinergic transmission.

Summary of Action:

• Enzyme inhibited: Acetylcholinesterase
• Effect: Increased acetylcholine
• Target receptors: Nicotinic and muscarinic receptors