OTHER MECHANISMS OF NEUROMUSCULAR BLOCKADE
Some drugs may interfere with the function of the ACh receptor without acting as an agonist or antag-onist. They interfere with normal functioning of the ACh receptor binding site or with the opening and closing of the receptor channel. These may include inhaled anesthetic agents, local anesthetics, and ket-amine. The ACh receptor–lipid membrane interface may be an important site of action.
Drugs may also cause either closed or open channel blockade. During closed channel blockade, the drug physically plugs up the channel, prevent-ing passage of cations whether or not ACh has acti-vated the receptor. Open channel blockade is use dependent, because the drug enters and obstructs the ACh receptor channel only after it is opened by ACh binding. The clinical relevance of open channel blockade is unknown. Based on laboratory experi-ments, one would expect that increasing the concen-tration of ACh with a cholinesterase inhibitor would not overcome this form of neuromuscular blockade. Drugs that may cause channel block in the labora-tory include neostigmine, some antibiotics, cocaine, and quinidine. Other drugs may impair the presyn-aptic release of ACh. Prejunctional receptors play a role in mobilizing ACh to maintain muscle contrac-tion. Blocking these receptors can lead to a fading of the train-of-four response.