Potentiation anticholinesterases

When amphotericin B or diuretics are administered with ACTH, the potential for hypokalemia is increased. There may be an increased need for insulin or oral antidiabetic drag s in the patient with diabetes who is taking ACTH. There is a decreased effect of ACTH when the agent is administered with the barbiturates. Profound muscular depression is possible when ACTH is administered with the anticholinesterase drugp. Live virus vaccines taken while taking ACTH may potentiate virus replication, increase vaccine adverse reaction, and decrease the patient s antibody response to the vaccine... 

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... 

All these observations underscore the potential for application of appropriate OPAs to the destruction of organophosphorus compounds with anticholinesterase activity (Cheng and Calomiris 1996). However, since, hydrolysis results in release of fluoride, the possibility of its subsequent incorporation into organic substrates to produce fluoroacetate and 4-fluorothreonine (Reid et al. 1995) may be worth consideration. 

The effect of administering different botulinum neurotoxin serotypes at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin. Aminoglycosides Cautiously perform coadministration of botulinum toxin type A and aminoglycosides or other agents interfering with neuromuscular transmission (eg, curare-like nondepolarizing blockers, lincosamides, polymyxins, quinidine, magnesium sulfate, anticholinesterases, succinylcholine chloride) because the effect of the toxin may be potentiated. 

In contrast to the beneficial effects of treatment with oximes in cases of OP intoxication, reports in the literatnre suggest that treatment of poisoning with certain anticholinesterase carbamates with some oximes should be avoided because they may actually potentiate carbamate action. Other oximes decrease carbamate toxicity. The effects observed are, in general, correlated with changes in the rates of carbamylation and decarbamylation in the presence of the various oximes . ... 

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. 

The actions of anticholinesterase agents on the cardiovascular system are complex. The primary effect produced by potentiation of vagal stimulation is bradycardia with a consequent decrease in cardiac output and blood pressure. However, potentiation of both parasympathetic and sympathetic ganglionic transmis-... 

Because anticholinesterase agents also inhibit plasma pseudo-ChE, they will potentiate the effects of succinylcholine by inhibiting its breakdown. This is important, for example, when succinylcholine is to be employed in patients who have previously received cholinesterase inhibitors for the treatment of myasthenia gravis or glaucoma. 

Treatment with guanidine may produce clinical improvement within 3 to 4 days. Side effects include paresthesia, gastrointestinal distress, renal tubular necrosis, and hyperirritability. The most serious effect is bone marrow depression, which is dose-related and potentially fatal. Aminopyridines have been used in clinical studies with some positive results. Corticosteroids and plasmapheresis may also be of some benefit, whereas anticholinesterase agents are only marginally effective. 

Rapid advances in chemistry during the nineteenth and twentieth centuries, coupled with the success of mustard gas as a toxic weapon in World War I, attracted attention to the warfare potential of chemical agents. This led to support for research on lethal nerve agents during and immediately after World War II. The research was followed by the development of treatment methods, and prominent among these was the use of cholinesterase reactivators to reverse the lethal effects of anticholinesterase nerve gases. 

Suxamethonium produces a typical depolarising block that is characterised by the appearance of fasciculations before the onset of block, absence of fade in response to tetanic and TOP stimulations, and potentiation of block by anticholinesterase drugs. 

The toxicity of diazinon may be affected by other substances. Some chemicals may increase the toxicity of diazinon in an additive manner. Anticholinesterase organophosphates and carbamates would be expected to act in an additive manner with diazinon with respect to its potential to induce cholinergic toxicity. 

Asymmetric induction has also been evaluated in the reaction of a-aryl substituted ketones, esters, and lactones (43). The potential of the method is demonstrated by the synthesis of some naturally occurring or nonnaturally occuring chiral compounds (Scheme 15). Similarly, asymmetric synthesis of ( — )-physostigmine, a clinically useful anticholinesterase agent, is accomplished by using phase-transfer alkylation of... 

On July 4, 2006, a paper written in an Australian chemical journal was published, describing the synthesis and structural identification of the exact compound described in claim 1. The publication also mentioned that the compound demonstrated anticholinesterase activity, and its potential use for cognition enhancement was described in excruciating detail. No other biological activity was disclosed. 

The toxins that inhibit the AChE are called anticholinesterase (anti-ChE) agents. They cause acetylcholine to accumulate in the vicinity of cholinergic nerve terminals, and thus are potentially capable of producing effects equivalent to excessive stimulation of cholinergic receptors throughout the central and peripheral nervous systems (Long, 1963). Nevertheless, several members of this class of compounds are widely used as therapeutics agents others that cross the blood-brain barrier have been approved or are in clinical trial for the treatment of Alzheimer s disease. 

Frawley, J.P., Fuyat, H.N., Hagan, E.C., Blake, J.R., Fitzhugh, O.G. (1957). Marked potentiation of mammalian toxicity from simultaneous administration of two anticholinesterase compounds. J. Pharmacol. Exp. Ther. 121 96-106. 

Anticholinesterase agents, such as 0.25% physostig-mine ointment, are also a viable treatment option and may be applied to the lid margins. Side effects, such as miosis and browache, may limit their use. Gamma benzene hexachloride should be avoided on treating the lid condition because of potential ocular irritation and... 

Anticholinesterase agents are potent drugs with many potential adverse effects iris cysts and anterior subcapsu-lar lens cataracts are the most serious and well known. Other significant but less common ocular manifestations include retinal detachment, angle-closure glaucoma, and uveitis. Common but less serious adverse effects include... 

The NRC staff organized the test chemicals into several pharmacologic classes the first two classes consisted of 15 anticholinesterase (Appendix A) and 24 anticholinergic (Appendix B) chemicals. Two expert panels were established (on anticholinesterases and on anticholinergics) with chairmen selected from the COT and members drawn from the scientific community on the basis of familiarity with some aspect of the pharmacologic class Involved or expertise In a discipline needed for proper evaluation of potential adverse health effects. 

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