Effect of anticholinesterases

Anticholinesterases are antagonists of the enzyme acetylcholinesterase—the enzyme which hydrolyses acetylcholine. If acetylcholine is not destroyed, it can return to activate the cholinergic receptor again and so the effect of an anticholinesterase is to increase levels of acetylcholine and to increase cholinergic effects (Fig. 11.44). 

Therefore, an antagonist at the acetylcholinesterase enzyme will have the same biological effect as an agonist at the cholinergic receptor. 

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Individuals with hereditary low plasma cholinesterase levels (Kalow 1956 Lehman and Ryan 1956) and those with paroxysmal nocturnal hemoglobinuria, which is related to abnormally low levels of erythrocyte acetylcholinesterase (Auditore and Hartmann 1959), would have increased susceptibility to the effects of anticholinesterase agents such as methyl parathion. Repeated measurements of plasma cholinesterase activity (in the absence of organophosphate exposure) can be used to identify individuals with genetically determined low plasma cholinesterase. 

Bhattacharya S. 1993. Target and non-target effects of anticholinesterase pesticides in fish. Sci Total Environ Supp. 1993 859-866. 

Lotti, M. (1992). Central neurotoxicity and behavioural effects of anticholinesterases. In B. Ballantyne and T.C. Marrs (Eds.) (1992). Clinical and Experimental Toxicology of Organophosphates and Carbamates 75-83. 

The essence of ChR action consists in dephosphorylation of the enzyme inhibited, which becomes apparent as restoration of its activity, i.e. ability to perform enzymatic hydrolysis. Therapeutic efficacy of ChR is associated with their capability to eliminate toxic effects of anticholinesterases on nicotine receptors. 

Stevens JT, Greene FE, Stitzel RE, et al. 1973. Effects of anticholinesterase insecticides on mouse and rat liver microsomal mixed function oxidase. In Deichmann W.B., Ed. Pesticides and the environment A continuing controversy. Proceedings of the 8th Inter-American Conference on Toxicology and Occupational Medicine, University of Miami School of Medicine, 489-501. 

Stevens JT, Stitzel K, McPhillips JJ. 1972a. Effects of anticholinesterase insecticides on hepatic microsomal metabolism. J Pharmacol ExpTher 181 576-583. 

Effect of anticholinesterases Block augmented Block antagonized... 

Complete symptomatic recovery usually occurs within a week increased susceptibility to the effects of anticholinesterase agents persists for up to several weeks after exposure. Daily exposure to concentrations that are insufficient to produce symptoms after a single exposure may result in the onset of symptoms. Continued daily exposure may be followed by increasingly severe effects. 

Caring for a demented patient is a heavy burden for family and care givers. Therapeutic management must include all available medical, medicosocial and institutional means. Communication is the key to a successful environment of cooperative care. For drug therapy, it is important to recall the real therapeutic effectiveness of anticholinesterase agents which can be reinforced by adjunction of non-drug therapeutic support. 

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

The only clinically available cholinergic therapy to date is an anticholinesterase (tacrine). Studies have shown short-term improvement in some aspects of memory and a delay in decline in some patients. It has been generally assumed that these effects are solely the result of enhancement of muscarinic mechanisms however, this assumption may be unwarranted. Direct muscarinic augmentation produces little measurable cognitive improvement and does not generally reproduce the memory-enhancing effects of anticholinesterases (Bruno et al. 1986 Tariot et al. 1988). 

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. 

It soon became evident that no available antidotes could block the pharmacologic activity of these chemicals, alleviate the signs and symptoms of toxicity, or restore normal bodily functions after exposure. Atropine readily antagonized the muscarinic actions, including those in the central nervous system (CNS), but elicited no reversal of the nicotinic effects. Better forms of therapy were sought, particularly to alleviate the nicotinic effects of anticholinesterase agents. 

Qll The number of normal acetylcholine receptors decreases as the disease progresses. This reduces the effectiveness of anticholinesterases. In such cases, immunosuppressant therapy, using a corticosteroid, can be used. This will help to reduce the formation of antibodies to acetylcholine receptors. In... 

O Neill, J.J. (1981). Non-cholinesterase effects of anticholinesterases. Fundam. Appl. Toxicol. 1 154-60. 

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. 

Separate from the acute effects of anticholinesterases upon the neuromuscular junction (discussed previously), two further syndromes involving the neuromuscular system have been associated with OP poisoning. These are (1) the intermediate syndrome (IMS), and (2) organophosphate-induced delayed polyneuropathy (OPIDP). 

Wheeler TG The behavioral effects of anticholinesterase insult following exposure to different environmental temperatures. Aviat Space Environ Med 58 54-59,1987 White RF, Feldman RG, Proctor SP Neurobehavioral effects of toxic exposures, in Clinical Syndromes in Adult Neuropsychology The Practitioner s Handbook. Edited by White RF. Amsterdam, Elsevier, 1992, pp 1-51... 

Meeter, E. (1971a) Some new effects of anticholinesterases in the whole animal, with special emphasis on the hypothermia inducing action in the rat. In Mechanisms of Toxicity. W. N. Aldridge (Ed.), Macmillan, London, pp. 29-38. 

Barstad, J.A.B., Cholinesterase inhibition and the effect of anticholinesterases on indirectly evoked single and tetanic muscle contractions in the phrenic nerve-diaphragm preparation from the rat, Arch. Int. Pharmacodyn., 128, 143, 1960. 

Wheeler, T.G., The behavioral effects of anticholinesterase insult following exposure to different environmental temperatures, Aviat. Space Environ. Med., 58, 54, 1987. 

Kirkby DL, Jones DN, Barnes JC, et al Effects of anticholinesterase drugs tacrine and E2020. the 5-... 

Effect of anticholinesterase agents Reversal of block No reversal... 

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