Neuromuscular blocking agents: a review.

The author provides a review of the mechanism of neuromuscular transnission, as well as the Nechanisn of action and differences between curare and succinylcholine. Effects of these two relaxants on various organs and tissues are discussed, as are their onset of action, duration, elimination, and clinical uses. In order to understand how skeletal muscle re-laxants act, the mechanism of neuromuscular transmission must first le understood. By way of review, a nerve impllulse consists of action potential electrical current. When this action potential arrives at the terminal membrane of the axon, it causes release of the quaternary Ibase acetylcholine from its storage protein at the membrane into the sub-neural space which is part of the extracellular space. This space is rich in sodium ions. Once in the suibneural space, acetylcholine crosses to the post-junctional memlrane or more specifically, the end-plate region of the muscle memlbrane and becomes adsorbed to cholinergic receptors in the membrane. The post-junctional membrane is semi-per-mealle and lprevents migration of sodium ions in and potassiumn ions out. Sodium predominates outside the membrane and potassium and other large impermeable anions predominate inside. At rest, uneven distribution of ions causes the outside to be positively charged while the interior is negative. The potential difference is called the resting Potential. The cholinergic receptors in the post-junc-tional membrane contain proteins and when acetyl-choline is adsorbed lby these proteins, their mol-ecilar (configurations are changed. The pore size and lperleability of the membrane is also changed. This causes the membrane to become depolarized. During the depolarization process, sodium migrates in and the potassium migrates out. Sodium moves in faster than potassium or chloride ions move out. The negative potential is reduced at first to-45 millivolts which results in end-plate potential. With further (lecrease to zero and an overshoot to ±30 millivolts, an action lotential results. The exterior of the membrane becomes negative and the interior lbeconles positive. The action potential spreads through the muscle fiber and contraction results. A lag of 2 or 3 milliseconds lpre-cedles contraction. The time of muscle contraction may take approximately 200 milliseconds. The estingl potential at the motor end-plate is restored much faster than the time it takes for muscle contraction. Acetylcholinesterase, which is p'resenlt in protein in the junctional membrane, becomes active and hydrolyzes acetylcholine into acetic acid and choline. This takes approximately .1 millisecond. This restores permeability to the post-junctional membrane so that it becomes positive and …