Nondepolarizing muscle relaxants

The duration of the effect of d-tubocurarine can be shortened by administering an acetylcholinesterase inhibitor, such as neostigmine (p.106). Inhibition of ACh breakdown causes the concentration of ACh released at the end plate to rise. Competitive displacement by ACh of d-tubocurarine from the receptor allows transmission to be restored. 

Unwanted effects produced by d-tubocurarine result from a non-immune-mediated release of histamine from mast cells leading to bronchospasm, urticaria, and hypotension. More commonly, a fall in blood pressure can be attributed to ganglionic blockade by d-tubocurarine. 

Pancuronium is a synthetic compound now frequently used and not likely to cause histamine release or ganglionic blockade. Increased heart rate and blood pressure are attributed to blockade of cardiac M2-choli-noceptors. 

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The effect of a standard dose of succinylcholine lasts only about 10 minutes. It is often given at the start of anesthesia to facil-Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms 

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Other nondepolarizing muscle relaxants include alcuronium, derived from the alkaloid toxiferin rocuroni-um, gallamine, mivacurium, and atra-curium. The latter undergoes spontaneous cleavage and does not depend on hepatic or renal elimination. 

Other drugs that may interact with cardiac glycosides include the following Albuterol, amphotericin B, beta-blockers, calcium, disopyramide, loop diuretics, nondepolarizing muscle relaxants, potassium-sparing diuretics, succinylcholine, sympathomimetics, thiazide diuretics, thioamines, and thyroid hormones. 

Drugs that may interact with nitrates include alcohol, alteplase, aspirin, beta-blockers, calcium channel blockers, dihydroergotamine, heparin, nondepolarizing muscle relaxants, phenothiazines, phosphodiesterase inhibitors (eg, sildenafil, tadalafil, vardenafil), and vasodilators. 

Drugs that may be affected by beta blockers include flecainide, gabapentin, haloperidol, hydralazine, phenothiazines, anticoagulants, benzodiazepines, clonidine, disopyramide, epinephrine, ergot alkaloids, lidocaine, nondepolarizing muscle relaxants, prazosin, sulfonylureas, and theophylline. 

The following agents may be affected by theophylline Benzodiazepines, -agonists, halothane, ketamine, lithium, nondepolarizing muscle relaxants, propofol, ranitidine, and tetracyclines. Probenecid may increase the effects of dyphylline. 

Acetaminophen Amiodarone Carbamazepine Cardiac glycosides Corticosteroids Dicumarol Disopyramide Doxycycline Estrogens Haloperidol Methadone Metyrapone Mexiletine Oral contraceptives Quinidine Theophylline Valproic acid Cyclosporine Dopamine Furosemide Levodopa Levonorgestrel Mebendazole Nondepolarizing muscle relaxant Phenothiazines Sulfonylureas... 

Drugs that may interact with vancomycin include aminoglycosides, anesthetics, neurotoxic/nephrotoxic agents, and nondepolarizing muscle relaxants. 

Newborn children are extremely sensitive to nondepolarizing muscle relaxants but may require three times as much depolarizing agent as an adult for an equivalent degree of block. Like newborn children, patients with myasthenia gravis are very sensitive to paralysis by d-tubocurarine but are resistant to succinylcholine. This altered responsiveness is probably due to the fewer number of functional AChRs at the end plate. Since neonates are very sensitive to d-tubocurarine, the dosage must be reduced and the degree of block closely monitored. 

Structures of some isoquinoline neuromuscular blocking drugs. These agents are all nondepolarizing muscle relaxants. 

Mivacurium, another isoquinoline compound, has the shortest duration of action of all nondepolarizing muscle relaxants (Table... 

Table 27-2 Comparison of a Typical Nondepolarizing Muscle Relaxant (Rocuronium) and a Depolarizing Muscle Relaxant (Succinylcholine). ...

Following the administration of succinylcholine, 0.75-1.5 mg/kg IV, transient muscle fasciculations occur over the chest and abdomen within 30 seconds, although general anesthesia and the prior administration of a small dose of a nondepolarizing muscle relaxant tends to attenuate them. As paralysis develops rapidly (< 90 seconds), the arm, neck, and leg muscles are initially relaxed followed by the respiratory muscles. As a result of succinylcholine s rapid hydrolysis by cholinesterase in the plasma (and liver), the duration of neuromuscular block typically lasts less than 10 minutes (Table 27-1). 

Inhaled (volatile) anesthetics potentiate the neuromuscular blockade produced by nondepolarizing muscle relaxants in a dose-dependent fashion. Of the general anesthetics that have been studied, inhaled anesthetics augment the effects of muscle relaxants in the following order isoflurane (most) sevoflurane, desflurane, enflurane, and halothane and nitrous oxide (least) (Figure 27-9). The most important factors involved in this interaction are the following (1) nervous system depression at sites proximal to the neuromuscular junction (ie, central nervous system) (2) increased muscle blood flow (ie, due to peripheral vasodilation produced by volatile anesthetics), which allows a larger fraction of the injected muscle relaxant to reach the neuromuscular junction and (3) decreased sensitivity of the postjunctional membrane to depolarization. 

Several diseases can diminish or augment the neuromuscular blockade produced by nondepolarizing muscle relaxants. 

Conversely, patients with severe burns and those with upper motor neuron disease are resistant to nondepolarizing muscle relaxants. This desensitization is probably caused by proliferation of extrajunctional receptors, which results in an increased dose requirement for the nondepolarizing relaxant to block a sufficient number of receptors. 

Debaene B, Plaud B, DillyMP, Donati F. Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. Anesthesiology. 2003 98 1042-1048. 

Phenytoin has been shown to interfere with neuromuscular transmission, and the drug has been reported to exacerbate myasthenia gravis. Lithium augments the effects of both depolarizing and nondepolarizing muscle relaxants and also reportedly unmasks myasthenia gravis. 

All of the inhalational anesthetic agents augment both the degree and duration of the neuromuscular blockade induced by the nondepolarizing muscle relaxants. 

Neonates are more sensitive to nondepolarizing muscle relaxants, and the response of the small infant to some extent resembles that of an adult patient with myasthenia gravis. 

Antibacterial Neuroleptic agent Antihypertensive Antilice/Antiscabies Nondepolarizing muscle-relaxing agent Antibiotic... 

Lefebvre HP, Cardona A, Toutain PL et al. (1992) A simple method for the quantitative evaluation of neuromuscular blockade in mice. J Pharm Toxicol Meth 27 129-133 Vizi ES, Tuba Z, Maho S et al. (2003) A new short-acting nondepolarizing muscle relaxant (SZ1677) without cardiovascular side effects. Acta Anaesthesiol Scand 47 291-300... 

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