Muscle, skeletal neuromuscular blockers

Paralysis usually is reserved for cases in whom sedation alone does not improve the effectiveness of mechanical ventilation. Neuromuscular blockers may lead to prolonged skeletal muscle weakness and should be avoided if possible. Patients requiring neuromuscular blockade are to be monitored and intermittent boluses should be utilized. 

The answer is d. (Hardman, pp 142—M3.) ACh will stimulate both muscarinic and nicotinic receptors. Skeletal muscle contraction is mediated through NM receptors, and ganglionic stimulation is an effect of NN receptors All of the other effects listed in the question occur following muscarinic receptor activation and will be blocked by atropine and scopolamine, both of which are muscarinic receptor antagonists. Skeletal muscle contraction will not be affected by these drugs rather, a neuromuscular blocker (e.g., tubocurarine) is required to antagonize this effect of ACh. 

Skeletal muscle relaxation (this requirement is currently met with the aid of skeletal muscle blockers used in conjunction with the anesthetic [see Neuromuscular Blockers, later]). 

Nonetheless, residual effects of the neuromuscular blocker can persist in some patients long after surgery is complete.6,13 The most serious complication is residual paralysis that is, skeletal muscle contraction remains depressed for several hours after the drug should have worn off.8,18 In extreme cases, this residual paralysis necessitates that the patient remain in intensive care with a mechanical ventilator to provide respiratory support. 

Two general types of neuromuscular blockers are discussed here. They are classified according to those that depolarize the skeletal muscle cell when binding to the cholinergic receptor and those that do not.37... 

Drugs discussed in this chapter are used to decrease muscle excitability and contraction via an effect at the spinal cord level, at the neuromuscular junction, or within the muscle cell itself. Some texts also classify neuromuscular junction blockers such as curare and succinylcholine as skeletal muscle relaxants. However, these drugs are more appropriately classified as skeletal muscle paralytics because they eliminate muscle contraction by blocking transmission at the myoneural synapse. This type of skeletal muscle paralysis is used primarily during general anesthesia using neuromuscular blockers as an adjunct in surgery was discussed in Chapter 11. Skeletal muscle relaxants do not typically prevent muscle contraction they only attempt to normalize muscle excitability to decrease pain and improve motor function. 

General anesthetics are rarely given alone. In addition to the analgesic agents just mentioned, benzodiazepines (midazolam, Versed diazepam, Valium ) are commonly used as adjuncts for the relief of anxiety, amnesia, and sedation prior to induction of anesthesia. Neuromuscular blockers (e.g., succinylcholine or pancuronium) can also be administered during the induction of anesthesia to relax skeletal muscles. 

Martyn JA, White DA, Gronert GA, Jaffe RS, Ward JM. Up-and-down regulation of skeletal muscle acetylcholine receptors. Effects on neuromuscular blockers. Anesthesiology 1992 76(5) 822 3. 

Skeletal muscle relaxants fall into three major categories those that reduce spasticity, those that cause neuromuscular blockade and those that work at the cellular level. Spasmolytic agents (e.g. metho-carbamol, guaifenesin) act centrally whereas neuromuscular blockers (e.g. succinylcholine (suxamethonium), pancuronium, atracurium) act at the neuromuscular end plate to produce muscular relaxation. Dantrolene falls into the third category and acts within the muscle cell itself to produce relaxation. 

If hyperthermia occurs as a result of excessive muscular hyperactivity, then skeletal-muscle paralysis is indicated. Use pancuronium, 0.1 mg/kg IV (see p 472), or another nondepolarizing neuromuscular blocker. Caution Be prepared to ventilate and endotracheally intubate the patient after muscle paralysis. 

Nicotinic cholinergic syndrome. Stimulation of nicotinic receptors at autonomic ganglia activates both parasympathetic and sympathetic systems, with unpredictable results. Excessive stimulation frequently causes depolarization blockage. Thus, initial tachycardia may be followed by bradycardia, and muscle fasciculations may be followed by paralysis. (Examples nicotine in addition, the depolarizing neuromuscular blocker succinyl-choline, which acts on nicotinic receptors in skeletal muscle.)... 

Another possible target for toxins are the receptors for neurotransmitters since such receptors are vital, especially for locomotion. In vertebrates the most strategic receptor is that for acetylcholine, the nicotinic receptor. In view of the breadth of action of the various conotoxins it is perhaps not surprising that alpha-conotoxin binds selectively to the nicotinic receptor. It is entirely possible that similar blockers exist for the receptors which are vital to locomotion in lower species. As mentioned previously, lophotoxin effects vertebrate neuromuscular junctions. It appears to act on the end plate region of skeletal muscle (79,59), to block the nicotinic receptor at a site different from the binding sites for other blockers (81). 

---