Nondepolarizing blockers

The effect of administering different botulinum neurotoxin serotypes at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin. Aminoglycosides Cautiously perform coadministration of botulinum toxin type A and aminoglycosides or other agents interfering with neuromuscular transmission (eg, curare-like nondepolarizing blockers, lincosamides, polymyxins, quinidine, magnesium sulfate, anticholinesterases, succinylcholine chloride) because the effect of the toxin may be potentiated. 

Nondepolarizing Blockers d-Tdbocurarine, Atracurium, Mivacurium, Pancuronium, Vecuronium, Rocuronium, and Rapacuronium... 

Nondepolarizing blockers are used to relax skeletal muscle for surgical procedures, to prevent dislocations and fractures associated with electroconvulsive therapy, and to control muscle spasms in tetanus. They do not produce anesthesia or analgesia. 

The degree of blockade can be influenced by body pH and electrolyte balance. Hypokalemia due to diarrhea, renal disease, or use of potassium-depleting diuretics potentiates the effect of nondepolarizing blockers. By contrast, hyperkalemia may oppose the actions of d-tubocurarine but enhance the end plate response to succinylcholine. The effectiveness of d-tubocurarine is reduced by alkalosis. 

Inhalation anesthetics, such as isoflurane, enflurane, halothane, and nitrous oxide, potentiate the action of nondepolarizing blockers, either through modification of end plate responsiveness or by alteration of local blood flow. The extent of potentiation depends on the anesthetic and the depth of anesthesia. The dose of muscle relaxant should be reduced when used with these anesthetics. 

Muscle contraction responses to different patterns of nerve stimulation used in monitoring skeletal muscle relaxation. The alterations produced by a nondepolarizing blocker and depolarizing and desensitizing blockade by succinylcholine are shown. In the train of four (TOF) pattern, four stimuli are applied at 2 Hz. The TOF ratio (TOF-R) is calculated from the strength of the fourth contraction divided by that of the first. In the double burst pattern, three stimuli are applied at 50 Hz, followed by a 700 ms rest period and then repeated. In the posttetanic potentiation pattern, several seconds of 50 Hz stimulation are applied, followed by several seconds of rest and then by single stimuli at a slow rate (eg, 0.5 Hz). The number of detectable posttetanic twitches is the posttetanic count (PTC)., first posttetanic contraction. 

Reverses the effects of nondepolarizing blockers, such as tubocurarine... 

Clinical use of muscle relaxants. Among the available neuromuscular blockers, succinylcholine displays the fastest onset of action. The patient can be intubated as early as 30-60 seconds after intravenous injection ( rapid sequence intubation ), which is important in emergency situations with an increased risk of aspiration (e.g., ileus, full stomach, head trauma). Postoperative muscle pain due to succinylcholine can be prevented by preinjection of a small dose of a nondepolarizing blocker ( precurarization ). In combination with propofol p. 218), rocuronium (p.184) creates intubation conditions comparable to those obtained with succinylcholine. 

Explain the mechanism of action of a nondepolarizing blocker in skeletal muscle relaxation. 

Atracurium, doxacurium, pancuronium, pipecuronium, d-tubocurarine, mivacurium. and metocurine are examples of nondepolarizing blockers. 

Describe the differences between depolarizing and nondepolarizing blockers from the standpoint of tetanic and posttetanic twitch strength. 

Figure 27-2. Drug interactions with the ACh receptor on the skeietal muscle end plate. Top ACh, the normal agonist, opens the sodium channel. Bottom left Nondepolarizing blockers bind to the receptor to prevent opening of the channel. Bottom right Succinylcholine causes initial depolarization (fasciculation) and then persistent depolarization of the channel, which leads to muscle relaxation. (Reproduced, with permission, from Katzung BG [editor] Basic Clinical Pharmacology, 8th ed. McGraw-Hill, 2001.)...

D. Reversal of Blockade The action of nondepolarizing blockers is readily reversed by increasing the concentration of normal transmitter at the receptors. This is best accomplished by administration of cholinesterase inhibitors such as neostigmine or pyridostigmine. In contrast, the paralysis produced by depolarizing blockers is increased by cholinesterase inhibitors during phase I. During phase II. the block produced by succinylcholine is usually reversible by cholinesterase inhibitors. 

Nondepolarizing blockers result in poorly sustained tetanic tension. They do not cause ganglionic stimulation or fasciculations at any time during their action. The answer is (C). 

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