Pyridostigmine anticholinesterase

Ray R, Clark III OE, Ford KW, Knight KR, Harris LW, Broomfield CA. A novel tertiary pyridostigmine derivative [3-(N,N-Dimethylcarbamyloxy)-l-methyl-A3-tetrahydropyridine] anticholinesterase properties and efficacy against soman. Fundam. Appl. Toxicol. 16 267-274, 1991. 

The failure of physostigmine to reverse BZ effects during the first 8 hours (Fig. 8) is interesting and unexplained. It reminds one of the Berry and Davies findings (in 1970 at the British labs in Porton Down) which showed that the reversible anticholinesterase pyridostigmine was paradoxically effective as a prophylactic agent in the event of nerve gas exposure (see ref. ). 

To block effects of anticholinesterase ay ents IV 0.2 mg for each 1 mg neostigmine or 5 mg pyridostigmine. 

Why choose pyridostigmine as the anticholinesterase (consider the duration of action, side-effects and the formulations available) ... 

Drug treatments include the use of anticholinesterase agents, such as neostigmine and pyridostigmine, in conjunction with an antimuscarinic drug such as atropine. 

Acute side effects occur from therapeutic doses in 1 % of patients. However, an excessive dose of an anticholinesterase drug results in a cholinergic crisis. The condition results from stimulation of muscarinic receptors and depolarization of the motor end plate. Symptoms of salivation, lacrimation, diaphoresis, weakness, and respiratory failure may result. Therapeutic use of pyridostigmine should be discontinued in the presence of nerve agent poisoning, as it may exacerbate symptoms in certain exposures. 

A number of types of parasympathomimetics are used. Muscarinic agonists used include carbachol and pilocarpine (see MUSCARINIC CHOLINOCEPTOR agonists) ANTICHOLINESTERASES include demecarium bromide, dyflos, ecothiopate iodide, pl sostigmine sulphate and pyridostigmine bromide. 

Cholinesterase reactivators are not used alone, and atropine is used concurrently to control parasympathomimetic toxic effects of anticholinesterases. Another approach is to use the carbonate anticholinesterase, pyridostigmine, prophylactically this prevents reaction of the enzyme with organophosphorous anticholinesterases. 

The positionS-substituted isomers of (255) and (256) frequently exhibit prominent miotic activity (which was taken as a reflection of anticholinesterase activity), whereas ortho- and para-substituted molecules are inert (313). Foldesand coworkers (322)concludedthat the optimum N -to-O O interatomic distance for compounds of the type (255) is 4.7 A. The meta isomers of these compounds meet this requirement, as does pyridostigmine (256), which is used clinically. Molecular models... 

Several medications, including anticholinesterases such as pyridostigmine bromide, are toxic to mice, but can be dialyzed from samples before testing. To avoid interfering with the mouse bioassay, a list of the patient s medications should accompany any diagnostic samples sent. All specimens require refrigeration at 4°C (37). 

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