Competitive neuromuscular blocking drugs

Mechanism of action of competitive neuromuscular blocking drugs. 

These are also known as the competitive neuromuscular blocking drugs. In a situation, when the impulses in the somatic nerve arrive at the specific region located in the nerve terminals in the motor end-plate, they eventually elicit the release of acetylcholine (ACh), which in turn gets diffused to the post-synaptic motor end-plate membrane. Thus, ACH combines with nicotinic cholinergic receptors to activate them that ultimately leads to the opening of transmembrane ion channels, ion-flow, and as a result affords membrane depolarization. Importantly, end-plate membrane depolarization is usually accompanied by depolarization of the muscle membrane and ultimately leads to muscle contraction In short, any plausible and feasible interruption of the aforesaid squence of events gives rise to the muscular paralysis. 

Muscle diseases. Patients with myasthenia gravis are very sensitive to (intolerant of) competitive but not to depolarising neuromuscular blocking drugs. Those with myotonic dystrophy may recover less rapidly than normal from central respiratory depression and neuromuscular block they may fail to relax with suxamethonium. 

The depolarising blockers (such as suxamethonium (succinylcholine)) act like acetylcholine to depolarise the motor endplate, but unlike acetylcholine, they are not immediately removed by cholinesterase. The anticholinesterase drugs increase the concentration of acetylcholine at the neuromuscular junction, which enhances and prolongs this type of blockade, and therefore anticholinesterases cannot be used as an antidote for this kind of blocker. Care should be taken if an anticholinesterase has been given to antagonise a competitive neuromuscular block prior to the use of suxamethonium, as the duration of the suxamethonium block may be prolonged. ... 

Reversal of this type of neuromuscular block can be achieved with anticholinesterase drugs, such as neostigmine, which prevent the destruction by cholinesterase of acetylcholine released at nerve endings, allow the concentration to build up and so reduce the competitive effect of a blocking agent. 

The manufacturer warns that irinotecan could possibly prolong the neuromuscular blocking effects of suxamethonium (succinylcholine) and antagonise the neuromuscular blockade of competitive (non-depolarising) drugs. This is based on the fact that irinotecan has anticholinesterase activity (see also Neuromuscular blockers + Anticholinesterases , p. 114, for an explanation of this mechanism). 

Ganglion blockers competitively block nicotinic cholinoceptors on postganglionic neurons in both sympathetic and parasympathetic ganglia. In addition, these drugs may directly block the nicotinic acetylcholine channel, in the same fashion as neuromuscular nicotinic blockers (see Figure 27-6). 

---