Why are patients with MG sensitive to nondepolariz-ing muscle relaxants and resistant to depolarizing muscle relaxants?
When an acetylcholine receptor is activated by two acetylcholine molecules, a small electrical current is estab-lished by the movement of ions through the channel of the open receptor. Endplate depolarization occurs when the summation of small currents from each open acetylcholine receptor reaches a threshold, which then results in mem-brane depolarization and muscle contraction. Because myasthenics have up to 80% fewer receptors available (decreased margin of safety) and 20% of receptors are required for neuromuscular transmission, a small amount of nondepolarizing muscle relaxant may block enough of the remaining receptors to inhibit endplate depolarization by acetylcholine. Similarly, any factor that minimally inter-feres with neuromuscular transmission and that may not cause clinical weakness in normal patients because of the large margin of safety may produce severe weakness in myasthenics because of the loss of excessive receptors.
Succinylcholine causes neuromuscular blockade by first depolarizing the motor endplate, then preventing rapid repolarization. Its agonist properties cause endplate depolar-ization by activating a sufficient number of acetylcholine receptors at the neuromuscular junction. With a decrease in the number of receptors available (downregulation), it would require an increase in the amount of agonist to increase the likelihood of sufficient agonist–receptor inter-actions for endplate depolarization. Thus, myasthenics are resistant to succinylcholine, and the ED95 in myasthenics is 2.6 times normal. The duration of succinylcholine may be prolonged in myasthenics for several reasons. Anticholinesterase drugs inhibit pseudocholinesterase, which is responsible for the metabolism of succinylcholine.
Plasmapheresis may decrease the amount of circulating pseudocholinesterase, which would also decrease the metab-olism of succinylcholine.