Neostigmine action

Released ACh is broken down by membrane-bound acetylcholinesterase, often called the true or specific cholinesterase to distinguish it from butyrylcholinesterase, a pseudo-or non-specific plasma cholinesterase. It is an extremely efficient enzyme with one molecule capable of dealing with something like 10000 molecules of ACh each second, which means a short life and rapid turnover (100 ps) for each molecule of ACh. It seems that about 50% of the choline freed by the hydrolysis of ACh is taken back into the nerve. There is a wide range of anticholinesterases which can be used to prolong and potentiate the action of ACh. Some of these, such as physostigmine, which can cross the blood-brain barrier to produce central effects and neostigmine, which does not readily... 

Topical routes of drug administration are where the drug is applied directly to the site of action. Many medicines are applied directly for example, hydrocortisone can be rubbed into the skin to relieve a local area of inflammation. The anticholinesterase neostigmine is dropped directly onto the eye surface to relieve glaucoma, a condition characterised by raised intra-ocular pressure which if untreated can lead to blindness. 

The reactions of AChE-biotests results in the red-brown product (Hettchet pigment). The reaction of AChE-biotests on inhibitors can be estimated visually. The residual activity of AChE in biotests after the action of different concentrations of eserine (physostigmine) and proserine (neostigmine) is seen in Fig. 3. 

The immediate effects on the action potential2 of the small muscles of the hand, and the ensuing changes in blood-cholinesterase activity, produced by an injection of neostigmine into the brachial artery were compared with those obtained with a similar injection of D.F.P. 

Action potentials of the small muscles of the hands were recorded. The muscles were fatigued by electrical stimulation of the nerves, and the effects of D.F.P. and of neostigmine,... 

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. 

Neuromuscular blockade A partial neuromuscular blockade was demonstrated after large IV doses of capreomycin. This action was enhanced by ether anesthesia (as has been reported for neomycin) and was antagonized by neostigmine. 

Loomis, T.A., Salafsky, B. 1963. Antidotal action of pyrldl-nium oximes in anticholinesterase poisoning comparative effects of soman, sarin, and neostigmine on neuromuscular function. 

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, by its peripheral vasodilatation action reduces the blood pressure and heart rate. 

Neostigmine does not cross blood-brain barrier, hence has no significant central action. 

It structurally and pharmacologically resembles neostigmine but has longer duration of action and less potent than neostigmine and better tolerated by myasthenia gravis patients. 

It is a longer acting neostigmine analogue and is used to treat atony of the bladder and intestine and its action lasts for 24 hours. It is given daily before breakfast. 

Enzymatic inactivation of transmitter Neostigmine Cholinergic synapses (acetylcholinesterase) Inhibits enzyme prolongs and intensifies transmitter action... 

Some cholinesterase inhibitors also inhibit butyrylcholinesterase (pseudocholinesterase). Flowever, inhibition of butyrylcholinesterase plays little role in the action of indirect-acting cholinomimetic drugs because this enzyme is not important in the physiologic termination of synaptic acetylcholine action. Some quaternary cholinesterase inhibitors also have a modest direct action as well, eg, neostigmine, which activates neuromuscular nicotinic cholinoceptors directly in addition to blocking cholinesterase. 

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