Depolarizing<unk> (Succinylcholine) Phase I block (depolarizing) Succinylcholine interacts with nicotinic receptor to open the channel and cause depolarization of the end plate, which later spread to and result in depolarization of adjacent membranes. As a result, there is disorganisation of contraction of muscle motor unit. Later, since succinylcholine is not able to be metabolised and removed effectively at the synapse, the depolarized membranes remain in state of depolarisation and cannot respond to additional impulses. Phase I blok effect can be increased by cholinesterase inhibitors which further delay the action of metabolism and removal by cholinesterase. Phase II block (desensitizing) Under continuous exposure to succinylcholine, the initial end plate depolarization is reduced, and repolarisation process is initiated. As a result of the widespread sustained depolarization the synapses ultimately begin repolarization. Once repolarized, the membrane’s is less susceptible to additional depolarization. Nondepolarizing<unk> In small clinical doses, nondepolarizing<unk> act predominantly at the nicotinic receptor site to compete with acetylcholine. In larger clinical dose, some of the<unk> <unk> can access the pore of the ion channel and cause blockage. This weakens<unk>  transmission and diminishes the effect of acetylcholinesterase inhibitors (e.g. neostigmine). Nondepolarizing<unk>  may also block prejunctional sodium channels which interfere with the mobilization of acetylcholine at the nerve ending. + Comparison of a typical nondepolarizing muscle relexant (tubocarine) and a depolarizing muscle relexant (succinylcholine). Tubocurarine Succinylcholine Phase I Phase II Administration of tubocurarine Additive Antagonistic Augmented Administration of succinylcholine Antagonistic Additive Augmented Effect of neostigmine Antagonistic Augmented Antagonistic Initial excitatory effect on skeletal muscle None Fasciculations None Response to a tetanic stimulus Un-sustained (fade) sustained (not fade) Un-sustained (fade) Post-tetanic facilitation Yes No Yes Rate of recovery 30-60 min 4-8 min > 20 min
Neuromuscular blocking agents
Neuromuscular-blocking drug
Cholinergic blocking drugs
Muscle relaxant
Antiarrhythmic agent
Antihypotensive agent
Steroid
Neuroleptanalgesic