Neostigmine reverses non-depolarizing neuromuscular blockade more reliably when a TOF (train-of-four) count of at least 2 twitches is present. The principal reason neostigmine CANNOT reverse a dense succinylcholine block is:

• A Succinylcholine occupies nicotinic receptors persistently in Phase I block
• B Neostigmine inhibits plasma cholinesterase, prolonging succinylcholine action ✓
• C Neostigmine competes with succinylcholine at the same receptor binding site
• D Neostigmine reduces acetylcholine synthesis in the nerve terminal

Explanation

Neostigmine is a reversible inhibitor of acetylcholinesterase; it also inhibits plasma (pseudo)cholinesterase, the enzyme responsible for metabolizing succinylcholine. Administration during a Phase I depolarizing block therefore prolongs and intensifies the block by slowing succinylcholine hydrolysis. This is a unique pharmacological paradox — the drug intended to reverse blockade actually worsens it when succinylcholine is the blocking agent.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.