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Anticholinesterases
Published in Kenneth J. Broadley, Autonomic Pharmacology, 2017
Myasthenia gravis is a disease of the neuromuscular junction characterized by weakness and fatigue of the skeletal muscles. There is a defect in neuromuscular transmission in which the number of postjunctional nicotinic receptors (NM) is reduced. It is now regarded as an autoimmune disease in which antireceptor antibodies present in the plasma of myasthenia gravis patients induce receptor degradation (Havard & Fonseca 1990). Diagnosis is assisted by the edrophonium test, whereby intravenous injections of the short-acting edrophonium (2 mg) leads to a brief improvement of muscle strength. The anticholinesterases, neostigmine, pyridostigmine, distigmine and ambenonium (Table 10.1), are the standard drugs for symptomatic treatment of myasthenia gravis. Their action results from the increased availability of Ach at the diminished receptors. They are given orally, despite the poor adsorption via the gastrointestinal tract. The muscarinic side-effects can be controlled with atropine, although these signs may be of value in recognizing overdose, which will have detrimental effects upon neuromuscular transmission arising from depolarizing block.
Efgartigimod for generalized myasthenia gravis with or without anti-acetylcholine receptor antibodies: a worldwide and Japanese perspective
Published in Expert Review of Clinical Immunology, 2022
Shigeaki Suzuki, Akiyuki Uzawa, Hiroyuki Murai
Numerous therapeutics have recently proven effective for the management of MG [10,11]. For example, in all individuals with MG, inhibitors of acetylcholinesterase (AChE) increase the amount of acetylcholine at neuromuscular endplates after motor nerve stimulation, and this improves muscle weakness. The AChE inhibitors neostigmine and ambenonium have exhibited different durations of action and different side-effect profiles, but the AChE inhibitor pyridostigmine has been preferred for symptomatic treatment. The aspects of improvement that have been reported in seronegative MG patients treated with these AChE inhibitors is so specific that they are used as diagnostic clues. It should be noted that many MuSK+ patients are intolerant of ACE inhibitors with worsening of weakness. The optimum doses of AChE inhibitors are a balance between providing increased muscle strength for the patient and the potential for side effects that results from the cholinergic stimulation of the autonomic nervous system.