Acetylcholine molecules that do not react with a receptor or are released from the binding site are destroyed almost immediately by the enzyme acetylcholinesterase in the junctional cleft. There are two distinct types of cholinesterase, namely acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). They are closely related in molecular structure but differ in their distribution, substrate specificity and functions. AChE is mainly membrane bound, relatively specific for acetylcholine and responsible for its rapid hydrolysis at cholinergic synapses. BChE or pseudocholinesterase is relatively non-selective and is found in many tissues. It hydrolyses butyrylcholine more rapidly than acetylcholine as well as other esters such as procaine and succinylcholine.

There are many conditions that can cause acute muscular weakness or paralysis. In primary neuromuscular disorders, the pathology can occur centrally in the brain down to the peripheral nerves including the neuromuscular junctions, and the muscle itself. Many systemic disorders, as shown in Table 17.1, can also bring about muscle weakness.

Drugs used to treat primary neuromuscular diseases work at different sites, depending on the pathology. In myasthenia gravis there is a transmission failure in the neuromuscular junction. This is due to an autoimmune response that destroys the nicotinic acetylcholine receptors. Drugs that can enhance cholinergic transmission, such as anticholinesterases, can improve neuromuscular function in this condition. However if the disease is too severe, the number of receptors remaining may become too few to produce an adequate end-plate potential, thus rendering anticholinesterase treatment ineffective. Other treatment modalities for myasthenia gravis involve the use of corticosteroids, intravenous immunoglobulins and plasmapheresis, with the aim of suppressing the amount of circulating immunoglobulins which attack the ACh receptors.