Neostigmine reversal

Morita T, Kurosaki D, Tsukagoshi H, Shimada H, Sato H, Goto F. Factors affecting neostigmine reversal of vecuronium block during sevoflurane anaesthesia. Anaesthesia (1997) 52, 538 3. 

Reversible cholinesterase inhibitors form a transition state complex with the enzyme, just as acetylcholine does. These compounds are in competition with acetylcholine in binding with the active sites of the enzyme. The chemical stracture of classic, reversible inhibitors physostigmine and neostigmine shows their similarity to acetylcholine. Edrophonium is also a reversible inhibitor. These compounds have a high affinity with the enzyme, and their inhibitory action is reversible. These inhibitors differ from acetylcholine in that they are not easily broken down by enzymes. Enzymes are reactivated much slower than it takes for subsequent hydrolysis of acetylcholine to happen. Therefore, the pharmacological effect caused by these compounds is reversible. 

The pharmacological properties of ambenonium are similar to neostigmine and pyridostigmine, and it works by reversible inactivation of cholinesterase. A synonym of this drug is ambenonium. 

Reversal of neuromuscular blockade Adults and children, 0.2 mg for each 1 mg neostigmine or 5 mg pyridostigmine. Administer IV simultaneously. 

As given in classification, these agents are of two type e.g. reversible and irreversible. The reversible anticholinesterases have a structural resemblance to acetylcholine, are capable of combining with anionic and esteratic sites of cholinesterase as well as with acetylcholine receptor. The complex formed with the esteratic site of cholinesterase is less readily hydrolyzed than the acetyl esteratic site complex formed with acetylcholine. Edrophonium forms reversible complex with the anionic site and has shorter duration of action. Also, neostigmine and edrophonium have a direct stimulating action at cholinergic sites. 

Neostigmine preceded by atropine to block muscarinic effects rapidly reverses muscle paralysis induced by competitive neuromuscular blockers (decurarization). 

The block of rocuronium is reversed with neostigmine 35-50 pg-kg-1 provided some spontaneous recovery has taken place. The reversal may be slowed in the presence of agents like sevoflurane, however discontinuation of sevoflurane before neostigmine administration results in fairly prompt recovery. 

Sacan O, Klein K, White PF Sugammadex reversal of rocuronium-induced neuromuscular blockade A comparison with neostigmine-glycopyrrolate and edrophonium-atropine. Anesth Analg 2007 104 569. [PMID 17312210]... 

In very high doses, aminoglycosides can produce a curare-like effect with neuromuscular blockade that results in respiratory paralysis. This paralysis is usually reversible by calcium gluconate (given promptly) or neostigmine. Hypersensitivity occurs infrequently. 

Saitoh Y, Hattori H, Sanbe N, et al. Reversal of vecuronium with neostigmine in patients with diabetes mellitus. Anaesthesia. 2004 59 750-754. 

Neostigmine Prostigmin Postoperative gastrointestinal and urinary atony, myasthenia gravis, reversal of neuromuscular blocking drugs... 

Respiratory acidosis enhances -tubocurarine- and pancuronium-induced neuromuscular block and opposes reversal by neostigmine. 

The reversible inhibitors, which have a short to moderate duration of action, fall into two categories. Type one, exemplified by edrophonium, forms an ionic bond at the anionic site and a weak hydrogen bond at the esteratic site of acetylcholinesterase. Type two, exemplified by neostigmine, forms an ionic bond at the anionic site and a hydrolyzable covalent bond at the esteratic site. The irreversible inhibitors, exemplified by organophosphorus compounds (diisopropyl fluorophosphate, parathion,... 

There is no definitive treatment to counteract the effects of GHB, although two drugs, neostigmine and physostigmine, have shown promise as potential reversal agents. If supportive medical care is delivered in a timely manner, the patient will usually recover several hours post-ingestion. 

Since mivacurium is metabolized by plasma cholinesterase, the interaction with the reversal drugs is unpredictable. On one hand, the neuromuscular blockade is antagonized because of increased acetylcholine concentrations in the synapse. On the other hand, mivacurium concentration may be higher because of decreased plasma cholinesterase breakdown of the muscle relaxant. The former effect usually dominates clinically, and mivacurium block is reversed by neostigmine. 

As mentioned in Part 2, there are drugs that can interfere with the inactivation of neurotransmitters. In that particular case the reversible cholinesterase inhibitor neostigmine was discussed within the context of treating myasthenia gravis. Excessive blockade of acetylcholinesterase at both muscarinic and nicotinic synapses results in a sustained excess of acetylcholine, which persistently activates the effector they innervate. Muscarinic stimulation results in excessive salivation, lacrimation, bronchiolar secretions, and bronchoconstriction. Nicotinic stimulation produces effects such as those described earlier for nicotine. 

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