Neuromuscular blocking Nicotine

These agents inhibit the muscarinic actions of acetylcholine at postganglionic parasympathetic neuroeffector sites including smooth muscle, secretory glands, and CNS sites. Large doses may block nicotinic receptors at the autonomic ganglia and at the neuromuscular junction. 

ACh receptors are present in the post-junctional membrane of the endplate, in the junctional folds. The nicotinic ACh receptor at the motor endplate has five subunits, two os, (3, 5 and . In addition, a Y subunit instead of an e subunit may be present in the so-called extra-junctional or the fetal receptor. The five subunits are arranged as a cylinder around a central funnel-shaped pore, the ion channel. The two a subunits each carry a recognition site which binds nicotinic agonists such as ACh and antagonists such as the neuromuscular blocking agents. Whilst ACh must bind to both subunits to produce an effect, it is sufficient for... 

While most of the muscle relaxants exert their predominant actions at the post-junctional nicotinic receptors, many also have variable pre-junctional effects. Although pre-junctional receptors have not been demonstrated there is putative evidence for their existence. The pre-junctional mechanisms are supposed to be responsible for the development of fade in response to tetanic or train-of-four (TOP) stimulation following administration of non-depolarising neuromuscular blocking drugs. 

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). 

Although the main site of action of the neuromuscular blocking agents is the nicotinic receptor of striated muscle, they may act at other cholinergic receptor sites throughout the body, such as the nicotinic receptors in the autonomic ganglia and the muscarinic receptors in the heart. 

Atropine is the mainstay of treatment 2 mg is given i.m. or i.v. as soon as possible and repeated every 15-60 min until dryness of the mouth and a heart rate in excess of 70 beats per minute indicate that its effect is adequate. A poisoned patient may require 100 mg or more for a single episode. Atropine antagonises the muscarinic parasympathomimetic effects of the poison, i.e. due to the accumulated acetylcholine stimulating postganglionic nerve endings (excessive secretion and vasodilatation), but has no effect on the neuromuscular block, which is nicotinic. 

A cholinergic crisis should be treated by withdrawing all anticholinesterase medication, mechanical ventilation if required, and atropine i.v. for muscarinic effects of the overdose. The neuromuscular block is a nicotinic effect and will be unchanged by atropine. A resistant myasthenic crisis may be treated by withdrawal of drugs and mechanical ventilation for a few days. Plasmapheresis or immimoglobulin i.v. may be beneficial by removing antireceptor antibodies (see above). 

Marshall IG. Pharmacological effects of neuromuscular blocking agents interaction with choUnoceptors other than nicotinic receptors of the neuromuscular junction. Anest Rianim 1986 27 19. 

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