Anticholinesterase drug

Obviously, by the very nature of their being, anticholinesterase drugs must be antagonists that is, they stop the enzyme from hydrolysing acetylcholine. This antagonism can be either reversible or irreversible depending on how the drug reacts with the active site. 

There are two main groups of acetylcholinesterases which we shall consider— carbamates and organophosphorus agents. 

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Sussman, J.L., Harel, M., and Silman, I. (1993). Three-dimensional structure of acetylcholinesterase and of its complexes with anticholinesterase drugs. Chemico-Biological Interactions 87, 187-197. 

A number of economic studies have been published that assess the economic impact of the introduction of anticholinesterase drugs on the care for people with dementia. Overall, they suggest that the introduction of the new drugs might be cost-neutral, while leading to modest improvements in the health-related quality of life of patients and carers. However, the reliability and robustness of the economic evidence need to be considered before concluding that any additional benefits of the new dmgs for dementia are indeed worth the cost. 

Stopping its degradation by cholinesterase with anticholinesterase drugs... 

Since any true (RBC) anticholinesterase drug should, in theory, provide the acetylcholine-sparing... 

Eserine (physostigmine) has a pyrroloindole skeleton. This alkaloid is used as an anticholinesterase drug, which is fairly important in the treatment of Alzheimer s disease. Eserine is synthesized in Physostigma venenosum and stored in the seeds of this leguminous plant. The synthesis pathway starts with tryptamine, which is transformed into eserine (Eigure 45). 

Reliable antidotes for botulism are not available. In some cases, anticholinesterase drugs may improve muscle strength, albeit temporarily. Guanidine and 4-aminopyri-dine also have limited usefulness. Management depends primarily on supportive measures, such as administering antitoxin and maintaining respiration. 

Anticholinesterase drugs are compounds that block AChE and inhibit the destruction of released ACh. The resultant higher neurotransmitter levels then increase the biological response. Anticholinesterases can therefore be considered as indirect cholinergic agents. Acetycholinesterase inhibitors can act by either of two mechanisms ... 

Both groups of AChE inhibitors are used therapeutically. One use of anticholinesterase drugs is in myasthenia gravis. This is an autoimmune disease caused by the development of antibodies against the patient s own ACh receptors, accompanied by disturbed neuromuscular transmission. The disturbance is caused by a reduction in the number of nerve terminals and an increase in the width of the synaptic cleft. Normally, nicotinic... 

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. 

Anticholinesterase drugs if administered in large doses or in the absence of muscle relaxants may produce fasciculations and even a depolarising type of block, similar to that with suxamethonium. Neostigmine prolongs the effect of suxamethonium. 

Flobbiger F Pharmacology of anticholinesterase drugs. In Zaimis E (editor) Handbook of Experimental Pharmacology. Vol. 42 Neuromuscular Junction. Springer, 1976. 

Eagger, S. A. Tacrine and older anticholinesterase drugs in dementia. Curr. Opin. Psychiat. 8 (1995) 264-270. 

The correct answer = A. Scopolamine has effects similar to those of atropine. Trimethaphan is a ganglionic blocker affecting nicotinic receptors atropine affects primarily muscarinic receptors. Physostigmine, an anticholinesterase drug, is the antidote for an excess of atropine. Atropine blocks the effects of acetylcholine and direct-acting agonists, such as carbachol. 

Angunawela II, Barker A. Anticholinesterase drugs for alcoholic Korsakoff syndrome. Int J Geriatr Psychiatry 2001 16 338-9. 

Myasthenia gravis is an autoimmime disease that affects the neuromuscular junction.A decrease in the number of available acetylcholine receptors due to circulating antibodies results in impaired neuromuscular transmission. This impairment manifests clinically as weakness and fatigability of volimtary musculature. Ocular and other muscles innervated by cranial nerves are most often involved. Although different treatment modalities are available, anticholinesterase drugs remain the mainstay of therapy. 

The diagnostic evaluation of myasthenia gravis includes a complete history and physical examination, objective evidence of circulating acetylcholine receptor antibodies, electrophysiologic evidence of abnormal neuromuscular transmission, and pharmacologic evaluation with anticholinesterase drugs. 

Blaber, L.C. and Bowman, W.C., 1963b Studies on the repetitive discharges evoked In motor nerve and skeletal muscle after Injection of anticholinesterase drugs. Brit. J. Pharmacol. 20 326-344. 

Reversal of this type of neuromuscular block can be achieved with anticholinesterase drugs, such as neostigmine, which prevent the destruction by cholinesterase of acetylcholine released at nerve endings, allow the concentration to build up and so reduce the competitive effect of a blocking agent. 

A more recent use of anticholinesterase drugs has been to improve cognitive function in patients with Alzheimer s disease, where both the degree of dementia and amyloid plaque density correlate with the impairment of brain cholinergic function. Donepezil and rivastigmine are licensed in the UK for this indication. Both are orally active and cross the blood-brain barrier readily (see p. 408). 

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