Edrophonium reversal

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. 

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. 

The organophosphate inhibitors are sometimes referred to as "irreversible" cholinesterase inhibitors, and edrophonium and the carbamates are considered "reversible" inhibitors because of the marked differences in duration of action. However, the molecular mechanisms of action of the three groups do not support this simplistic description. 

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]... 

Edrophonium Enlon, Reversol, Tensilon Myasthenia gravis, reversal of neuromuscular blocking drugs... 

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,... 

DONEPEZIL SUXAMETHONIUM Possible t efficacy of suxamethonium Suxamethonium is metabolized by cholinesterase parasympatho-mimetics inhibit cholinesterase and so prolong the action of suxamethonium Avoid co-administration. Ensure that the effects of suxamethonium have worn off before administering a parasympathomimetic to reverse non-depolarizing muscle relaxants. A careful risk-benefit analysis should be made before considering the use of suxamethonium for emergency anaesthesia in patients taking parasympathomimetics. The short half-life of edrophonium means that it can be used to diagnose suspected dual block with suxamethonium... 

In another investigation, irreversible inhibition of enzyme activity was prevented by coincubation with reversible agents that either sterically block (edrophonium and decamethonium) or alio sterically modify (propidium) the acetylcholine site (Barnett and Rosenberry, 1977). Enzyme activity was not regenerated by incubation with oxime reactivators therefore, the mechanism of irreversible inhibition does not appear to involve acylation of the active site serine. 

The neostigmine test is used more often to help evaluate limb strength in suspected myasthenics. Neostigmine, a reversible cholinesterase inhibitor with a duration of action longer than that of edrophonium, can be administered either intravenously or intramuscularly. The usual adult dose is 1.5 mg intramuscularly in combination with 0.5 mg atropine to prevent cholinergic-induced side effects. 

Simple quaternary compounds, such as edrophonium, form electrostatic bonds with the anionic site of the enzyme and hydrogen bonds with Che imidazole nitrogen atom of the esteraclc site. In all such cases. Inhibition is rapidly reversible, and such drugs have a very short duration of inhibitory action ... 

Ciclosporin can cause considerable prolongation of the neuromuscular paralysis induced by pancuronium (42) in one patient (and also in another given vecuronium). Reversal required both neostigmine and edrophonium. Subsequently, recurarization occurred (SEDA-14, 116). Contributing factors could have been the solvent Cremophor EL in the ciclosporin formulation (Sandimmun) and minor renal dysfunction. 

Jones RM, Cashman JN, Casson WR, Broadbent MP. Verapamil potentiation of neuromuscular blockade failure of reversal with neostigmine but prompt reversal with edrophonium. Anesth Analg 1985 64(10) 1021-5. 

Quaternary ammonium derivatives and basic drugs Atropi ne.scopolami ne,meth-ylatropine,various drugs Pyri dos ti gmine,neosti gmi-ne,edrophonium and their 3-hydroxy metabolites Separation by ion-pair adsorption chromatography Separation by reversed-phase ion--pair HPLC(Fig.4.7) Analysis in biological fluids... 

Reversible AChE inhibitors ( in Figure II-2-1) include edrophonium, physostigmine, and neostigmine. Irreversible AChE inhibitors include echothiophate, malathion, and parathion. 

Direct activators bethanechol (M), methacholine (M and N), nicotine (N), pilocarpine (M) AChE inhibitors reversible—edrophonium, physostigmine, neostigmine AChE inhibitors irreversible—echothiophate, malathion, parathion... 

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