Neuromuscular transmission and its pharmacological blockade. Part 1: Neuromuscular transmission and general aspects of its blockade.

Blockade of neuromuscular transmission is an important feature during anaesthesia and intensive care treatment of patients. The neuromuscular junction exists in a prejunctional part where acetylcholine is synthesized, stored and released in quanta via a complicated vesicular system. In this system a number of proteins is involved. Acetylcholine diffuses across the junctional cleft and binds to acetylcholinereceptors at the postjunctional part, and is thereafter metabolized by acetylcholinesterase in the junctional cleft. Binding of acetylcholine to its postjunctional receptor evokes muscle contraction. Normally a large margin of safety exists in the neuromuscular transmission. In various situations, apart from up-and-down regulation of acetylcholine receptors, adjustment of acetylcholine release can occur. Pharmacological interference can interrupt the neuromuscular transmission and causes muscle relaxation. For this reason both depolarizing and non-depolarizing muscle relaxants are clinically used. The characteristics of an ideal clinical muscle relaxant are defined. In the description of the pharmacology of the relaxants the importance of pharmacodynamic and pharmacokinetic parameters are defined. Stereoisomerism plays a role with the relaxants. Toxins and venoms also interfere with neuromuscular transmission, through both pre- and postjunctional mechanisms.