Myasthenia Gravis

Myasthenia gravis is an autoimmune disease in which antibodies recognize nicotinic cholinoreceptors on skeletal muscle. This decreases the number of functional receptors and consequently decreases the sensitivity of the muscle to ACh. Muscle weakness and rapid fatigue of muscles during use are characteristics of the disease. Anticholinesterase agents help to alleviate the weakness by elevating and prolonging the concentration of ACh in the synaptic cleft, producing a greater activation of the remaining nicotinic receptors. By contrast, thymectomy, plasmapheresis, and corticosteroid administration are treatments directed at decreasing the autoimmune response.

Anticholinesterase agents play a key role in the diagnosis and therapy of myasthenia gravis, because they increase muscle strength. During diagnosis, the patient's muscle strength is examined before and immediately after the intravenous injection of edrophonium chloride. In myasthenics, an increase in muscle strength is obtained for a few minutes.

The pronounced weakness that may result from inadequate therapy of myasthenia gravis (myasthenic crisis) can be distinguished from that due to anticholinesterase overdose (cholinergic crisis) by the use of edrophonium. In cholinergic crisis, edrophonium will briefly cause a further weakening of muscles, whereas improvement in muscle strength is seen in the myasthenic patient whose anticholinesterase therapy is inadequate. Means for artificial respiration should be available when patients are being tested for cholinergic crisis.

Pyridostigmine and neostigmine are the major anti-cholinesterase agents used in the therapy of myasthenia gravis, but ambenonium can be used when these drugs are unsuitable. When it is feasible, these agents are given orally. Pyridostigmine has a slightly longer duration of action than neostigmine, with smoother dosing, and it causes fewer muscarinic side effects. Ambenonium may act somewhat longer than pyri-dostigmine, but it produces more side effects and tends to accumulate.

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