Cholinesterase regenerators

Parenteral 50 mg/mL Cholinesterase Regenerator Pralidoxime(generic, Protopam)... 

Cholinesterase regenerator A chemical antagonist that binds the phosphorus of organophosphates and displaces acetylcholinesterase... 

Figure 8-1. Subclasses of anticholinergic drugs and the cholinesterase regenerator discussed in this chapter. (The cholinesterase regenerators are not considered a part of the anticholinergic group.)...

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The rate of regeneration of plasma cholinesterase in man after its depression by D.F.P. was found to resemble the rate of regeneration of serum albumin in experimental animals that have been depleted by plasmaphoresis.1... 

The rate of regeneration of serum cholinesterase in normal subjects after the administration of D.F.P. by intramuscular injection has been determined.1 The regeneration rate of serum cholinesterase after the administration of D.F.P. to patients with liver damage has also been determined and is found to be significantly lower than normal. 

It will be shown below that D.F.P. is rapidly destroyed in vitro and in vivo.2 Therefore, the recovery of serum cholinesterase activity is not representative of a reversal of enzyme inhibition, but is indicative of synthesis of new enzyme proteins. Since the regeneration rate of serum cholinesterase in patients with liver damage is significantly depressed as contrasted with that in the normal patient, it is concluded that the ability of such patients to synthesize this particular enzyme protein is decreased. This constitutes evidence for the view that the fiver is a primary locus for the formation of serum cholinesterase. 

While atropine blocks the muscarinic effects, 2-PAM regenerates cholinesterase enzymes in sympathetic, parasympathetic, and central nervous system sites. 

A second class of compounds, capable of regenerating active enzyme from the organophosphorus-cholinesterase complex, is also available to treat organophosphorus poisoning. These oxime agents include pralidoxime (PAM), diacetylmonoxime (DAM), and others. 

Pralidoxime Very high affinity for phosphorus atom but does not enter CNS Regenerates active AChE can relieve skeletal muscle end plate block Usual antidote for early-stage (48 h) cholinesterase inhibitor poisoning Intravenous every 4-6 h Toxicity Can cause muscle weakness in overdose... 

PAM is given to regenerate inhibited cholinesterase (acetylcholinesterase) enzyme at all affected sites (Schenker et al. 1992 Shankar 1967, 1978). The available information sufficiently satisfies the need for methods of reducing toxic effects. Therefore, further studies in this regard are not required. 

Thus, the inhibition of cholinesterase enzymes by organophosphorus compounds may last for several days or weeks, and repeated dosing at shorter intervals than the half-life of regeneration of the enzyme leads to accumulation of the inhibition until the toxic threshold of around 50% is reached. 

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