Anticholinesterases inhibitors

To be useful to those concerned with choices in the allocation of health and social care resources, the data for economic evaluations need to be timely, relevant, credible and accurate (Davies, 1998). As a minimum, the costs associated with the interventions should be estimated from activity data, which quantify resources used, and price or unit cost data. Often evidence from well-controlled prospective trials with high internal validity is required to establish whether differences in economic end points are directly attributable to the interventions. However, the economic evaluations of acetylcholinesterase inhibitors estimated costs from retrospective analysis of available datasets Qonsson et al, 1999b), analysis of published literature (e.g. Stewart et al, 1998) and expert opinion (e.g. O Brien et al, 1999 Neumann et al, 1999). This means that it is not clear whether differences in costs were due to the anticholinesterase inhibitors or to other factors such as availability of services in different areas, the living situation of the patient, or disease severity. 

Three of the four studies discussed above measured the benefits of anticholinesterase inhibitors as time spent in condition less than severe . While this provides a measure of health status, it does not give an assessment of the value to patients or society of the health... 

Shintani EY, Uchida KM. (1997). Donepezil an anticholinesterase inhibitor for Alzheimer s disease. 

Because of accidental exposure to insecticides by children or by agricultural workers, an appreciation of the toxicities of insecticide anticholinesterase inhibitors is medically relevant. 

Utility Anticholinesterase Inhibitor in Treating Neurological Disorders... 

Triorlhocresyl phosphate (TOCP [CAS 78-30-8]) Inhibits acetylcholinesterase (see p 291). Potent neurotoxin causing delayed, partially reversible peripheral neuropathy by all routes. 0.1 mg/m, S 40 mg/m Colorless viscous liquid. Odorless. Not combustible. Although an anticholinesterase inhibitor, it is widely used as a chemical additive and in chemical synthesis. 

The anticholinesterase inhibitors (organophosphorous and carbamate), have come into widespread use in the last decades, because they are less persistent in the environment than other pesticides, such as organochlorine. However their presence in water and food is a potential hazard to human health and there is a growing interest in their rapid and accurate determination. Standard methods, based on gas chromatography (GC), are very reliable but there is the need for fast and innovative methods. The use of enzymatic biosensors, and especially electrochemical biosensors, for organophosphorus and carbamate pesticides detection has been reported by many authors [22-26]. 

The toxic organic phosphorus compounds act as powerful inhibitors of cholinesterase, an enzyme found predominantly in the nervous tissue of animals, including insects. This enzyme hydrolyzes acetylcholine, which plays an essential role in the transmission of nerve impulses. The toxicity of compounds in this series can be largely accounted for on the basis of their anticholinesterase activity (7,8,12,14, SI). 

Anticholinesterase A drug that inhibits the enzyme acetylcholinesterase, which normally inactivates acetylcholine at the synapse. The effect of an anticholinesterase (or cholinesterase inhibitor) is thus to prolong the duration of action of the neurotransmitter. An example is rivastigmine, used in the treatment of Alzheimer s disease. 

Depending upon the part of the enzyme with which the anticholinesterases react, the latter can be readily classified. In the first place there are a few compounds (e.g. mercuric chloride) that combine with the enzyme at sites other than those mentioned, thus providing a type of inhibition which is noncompetitive with the substrate. The vast majority of inhibitions, however, compete with the substrate for positions on the enzyme. Depending upon the point of attachment, competitive inhibitors have been classified thus 3... 

It may be noted that many of the anticholinesterases of the competitive type are equally potent as inhibitors of a- and / -cholinesterases. We should add, however, that the existence of an anionic site in / -cholinesterases has been questioned.1... 

Irreversible anticholinesterases include the organophosphorus inhibitors and ambenonium, which irreversibly phosphorylate the esteratic site. Such drugs have few clinical uses but have been developed as insecticides and nerve gases. Besides blocking the muscarinic receptors with atropine sulphate in an attempt to reduce the toxic effects that result from an accumulation of acetylcholine, the only specific treatment for organopho-sphate poisoning would appear to be the administration of 2-pyridine aldoxime methiodide, which increases the rate of dissociation of the organophosphate from the esteratic site on the enzyme surface. 

It Is well known that phosphorothlonate insecticides such as parathlon (, 0-diethyl p-nitrophenyl phosphorothloate) and malathion [0, -dimethyl -(l,2 -dlcarbethoxy)ethyl phosphoro-dithioate] are Intrinsically poor inhibitors of acetylcholinesterase and in vivo activation to the respective anticholinesterases paraoxon and malaoxon is required before animals exposed to the phosphorothionates are intoxicated. Since metabolic activation is essential to the biological activity of these thiono sulfur-containing organophosphorus insecticides, compounds of this type may be considered as propesticides or, more specifically, prolnsectlcldes. 

Anticholinesterase agents of all classes can initiate antidromic firing of action potentials in motor neurons, possibly due to an activation of prejunctional ACh receptors that are activated by the elevated synaptic ACh. Quaternary ammonium inhibitors can also act as agonists at these receptors. The initiation of antidromic firing may be a mechanism by which cholinesterase inhibitors produce fasciculation of skeletal muscle. 

Anticholinesterase agents can be employed in the treatment of adynamic ileus and atony of the urinary bladder, both of which may result from surgery. Neostigmine is most commonly used, and it can be administered subcutaneously or intramuscularly in these conditions. Cholinesterase inhibitors are, of course, contraindicated if mechanical obstruction of the intestine or urinary tract is known to be present. 

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