Which mechanism best describes how neostigmine reverses nondepolarizing neuromuscular blockade?

Which mechanism best describes how neostigmine reverses nondepolarizing neuromuscular blockade?

• A. Inhibits acetylcholinesterase
• B. Blocks acetylcholine receptors
• C. Mimics acetylcholine
• D. Inhibits calcium release from the sarcoplasmic reticulum

Answer: (A)

Increasing acetylcholine at the neuromuscular junction to outcompete the blocking agent is how reversal works. Neostigmine does this by inhibiting acetylcholinesterase, the enzyme that breaks down acetylcholine. With the enzyme blocked, acetylcholine accumulates in the synaptic cleft, so more of it can bind to nicotinic receptors on the motor endplate and overcome the competitive blockade produced by nondepolarizing agents, restoring muscle contraction. This is different from blocking the receptors, mimicking acetylcholine, or inhibiting calcium release from the sarcoplasmic reticulum, none of which describe neostigmine’s action. It’s common to give an anticholinergic alongside to counteract muscarinic side effects from increased acetylcholine.

Increasing acetylcholine at the neuromuscular junction to outcompete the blocking agent is how reversal works. Neostigmine does this by inhibiting acetylcholinesterase, the enzyme that breaks down acetylcholine. With the enzyme blocked, acetylcholine accumulates in the synaptic cleft, so more of it can bind to nicotinic receptors on the motor endplate and overcome the competitive blockade produced by nondepolarizing agents, restoring muscle contraction. This is different from blocking the receptors, mimicking acetylcholine, or inhibiting calcium release from the sarcoplasmic reticulum, none of which describe neostigmine’s action. It’s common to give an anticholinergic alongside to counteract muscarinic side effects from increased acetylcholine.